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REVIEW | doi:10.20944/preprints202103.0031.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: Dermal wound; Nanocuetical; Wound biochemistry; Wound healing mechanism
Online: 1 March 2021 (14:21:46 CET)
Dermal wound healing describes the progressive repair and recalcitrant mechanism of damaged skin and eventually reformatting and reshaping the skin. Many probiotics, nutraceuticals, metal nanoparticles have been associated with improved healing process of intra and inter tissue wounds. Despite the vast nature on material based wound healing mediators, the exact mechanism on material-cellular interaction is still point of repent issue particularly in diabetics and pathological condition. The use of bioengineered alternative agents will likely only continue to dominate the outpatient and perioperative management of chronic, recalcitrant wounds as new additional products continue to cut costs and improve wound healing process. This review article provides an update of the various remedies with confirmed wound healing activities by a diverse group of agents from previous experiments conducted by various researchers
ARTICLE | doi:10.20944/preprints202311.1288.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: Phyllanthus emblica; cryogel; wound dressing materials; wound healing
Online: 21 November 2023 (07:43:24 CET)
Phyllanthus emblica (P. emblica) has been described in many studies to have multiple therapeutic activities and is considered an important part of Ayurvedic and Unani medicinal systems. This study successfully synthesized P. emblica loaded polyvinylalcohol/gelatin based cryogels (PVA/Gel/P.emblica) to examine their potential in wound dressing applications. Swelling tests, Brunauer-Emmett-Teller (BET) and morphology analysis were conducted within the scope of characterization studies. In vitro cell culture studies were performed using HaCaT cells to illustrate the suitability of the synthesized cryogels as wound dressing material. The swelling tests and BET analysis results showed that swelling and surface area properties of cryogels increased with increasing P. emblica amounts. Morphological results displayed that the cryogels had a dense, interconnected pore morphology and a macroporous structure. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), trypan blue exclusion and live-dead assay results revealed that adding of P. emblica into cryogels led to enhanced cell proliferation, increased cell number, and improved cell viability. Based on the phase contrast microscope, scanning electron microscope (SEM), immunofluorescence and giemsa staining images, it was observed that P. emblica promoted cell attachment, proliferation and penetration. In conclusion, it has been shown that PVA/Gel/P.emblica cryogels are suitable for use as wound dressing materials and can be developed with further studies.
ARTICLE | doi:10.20944/preprints202110.0417.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Diabetic wound; Achyranthes aspera; wound healing; burn wound; cotton; pellet granuloma; carrageenan-induced paw edema; Acute toxicity
Online: 27 October 2021 (14:16:41 CEST)
Introduction: Wound healing is a multifaceted biological process, and diabetic wounds add more complexity to it. In diabetic wounds, the combination of chloroform fractions of Achyranthes aspera L. (A.aspera) leaves with β-Glucans has not been investigated. The additive effect of these two (A.aspera + β-Glucans) would benefit the inflammatory phase of diabetic wounds, as improper treatment will lead to chronic injuries. Therefore, the goal of this research work was to assess the in-vivo wound healing and anti-inflammatory effects of a combination of chloroform fractions of A.aspera leaves and β-Glucans in a variety of wound models in STZ-induced diabetic rats. Methods: Preliminary phytochemical analyses of A.aspera were conducted to identify various phytoconstituents in the test extract. Acute and sub-acute dermal toxicity tests of A.aspera were carried out on mice and rats, respectively, to see whether there were any abnormalities. Excision and incision wound models, cotton pellet-induced granuloma models, rat paw edema and burn wounds were used to test wound healing and anti-inflammatory actions. To induce diabetes, streptozotocin (STZ) was administered intraperitoneally at a dosage of 65 mg/kg (i.p.). A.aspera (10% w/w) and β-Glucans (2% w/w) ointments were tested separately and in combination for wound healing activities. Silver sulfadiazine (1 % w/w) ointment was used to treat the positive control groups. Excision wound model rats that had been treated with basic ointment were used as negative controls, as were incision wound model rats that had not been treated. A.aspera (400 mg/kg, po) and β-Glucans (30 mg/kg, po) were tested separately and in combination for anti-inflammatory efficacy. Positive control groups were given indomethacin (10 mg/kg, po) for cotton pellet-induced granuloma and rat paw oedema models. Negative controls for both anti-inflammatory activity models were provided 2% Tween 80. The groups were made up of six rats, and the treatments were given topically and orally to assess wound healing and anti-inflammatory effects. The levels of hydroxyproline and hexosamine and the antioxidant enzymes (SOD and CAT) in the granulation tissue were measured in excision wound model. Healed excision wound skin was examined histopathologically. Results: The A.aspera and β-Glucans combination resulted in a significant percentage of wound contraction and a shorter epithelialization time (P<0.01). The combination was found to be the most effective, with the highest percentage of edema reduction (55 %; p<0.01). The combination also exhibited favourable hydroxylamine, hexosamine and anti-oxidant profiles supported by histopathology data. Conclusion: This research showed that the immunomodulatory effect of β-Glucans had significantly enhanced the wound healing, anti-inflammatory, and anti-oxidant potential of A.aspera in diabetic wounds.
ARTICLE | doi:10.20944/preprints202306.0308.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: Wound healing; Antibacterial; Hydrogel; Meshfill; Silver nanocomposite
Online: 5 June 2023 (10:34:40 CEST)
Introduction: Among the many factors that may limit effective wound healing in patients with chronic ulcers, bacterial infection and poor cell recruitment are primary causes that contribute to prolonged healing. Thus, a novel strategy that aims to prevent bacterial infection within the wound, while at the same time providing structural scaffolding that promotes endogenous tissue repair, would be of great interest. Here, we developed a thermo-sensitive silver nanoparticle hydrogel composite as an antibacterial nutritional scaffold for the wound that contains all nutrients required for cell growth while preventing bacterial infection with the ability to fill up all the cavities and void areas in wounds regardless of their geometry. Methods: Silver nanoparticles (AgNPs) were synthesized by chemical reduction. After characterization, silver hydrogel nanocomposite was developed by reconstitution of collagen-based hydrogel powder in a nanoparticle suspension of varying AgNPs concentrations (200, 400, and 600 ppm). The antibacterial activity of the formulations was examined in vitro and in vivo in subcutaneous implant infected model. The wound healing efficacy of the hydrogel nanocomposite was also evaluated using a splinted wound model in rats through comparison of clinical wound measurements and histological assessments. Cytocompatibility assay and biochemical analysis of blood at the end of in vivo wound healing study were performed to evaluate the safety of formulations. Results: The synthesized nanoparticles were spherical and stable. While hydrogel alone did not show any bacterial reduction in vitro, the inhibition of bacterial growth was significant in all silver hydrogel nanocomposites compared to controls (p <0.05) and was dose-dependent, with maximum reduction observed in the 600 ppm group (4.56±0.26 LOG CFU/mL, P<0.001). All concentrations of AgNPs hydrogel composites showed significant antibacterial activity in vivo as well (P<0.0001). Treatment of splinted wounds with AgNPs hydrogel composite resulted in faster wound closure and accelerated wound re-epithelialization. The formulations were non-cytotoxic and did not differ significantly in hematological and biochemical factors from the control group in in vivo study. Conclusions: By presenting promising antibacterial and wound healing activity, silver hydrogel nanocomposite offers a safe therapeutic option that can be used as a functional scaffold for an acceleration of wound healing.
ARTICLE | doi:10.20944/preprints202308.1448.v2
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Chronic wounds; Dermal samples; Fibroblast cells; Low-Level Laser Therapy (LLLT); Migration; Proliferation; Therapeutic intervention; Wound healing; Wound margins; Wound tissue
Online: 30 August 2023 (02:33:14 CEST)
This study aimed to evaluate the proliferation and migration of fibroblast cells derived from chronic wounds and investigate the impact of low-level laser therapy (LLLT) on their growth and migration. A total of 60 dermal samples were obtained from three sites of chronic pressure ulcers and diabetic ulcers in 20 patients. Following collection in the operating room, the dermal samples were isolated using the procedure described by Freshney RI. Fibroblasts from the wound base (Site 1) exhibited a slow proliferation rate and a decrease in proliferative capacity. Fibroblasts from wound margins (Site 2) and adjacent healing skin (Site 3) could be successfully isolated and maintained for multiple generations without any morphological changes. Fibroblasts from chronic wounds at Sites 2 and 3 showed slower proliferation rates and reduced migration capabilities compared to normal dermal fibroblasts (control samples). The fibroblast cells were exposed to LLLT at different energy levels (2.5, 3, and 3.5 J/cm2). The laser-treated groups demonstrated a significantly higher increase in cell count compared to the control sample, with the highest increase observed at an energy level of 3 J/cm2. These findings suggest that LLLT at an energy level of 3 J/cm2 could effectively enhance fibroblast migration, indicating its potential as a therapeutic intervention for chronic wounds.
REVIEW | doi:10.20944/preprints202104.0703.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Cell mogration; Cutaneous wound healing; Wound healing assay; lab-on-a-chip; Skin; Microvasculature; Microfluidics
Online: 27 April 2021 (10:17:44 CEST)
Cutaneous wound healing is a complex multi-stage process involving direct and indirect cell communication events with the aim of efficiently restoring the barrier function of the skin. One key aspect in cutaneous wound healing is associated with cell movement and migration into the physically, chemically and biologically injured area resulting in wound closure. Understanding the conditions under which cell migration is impaired and elucidating the cellular and molecular mechanisms that improve healing dynamics is therefore crucial in devising novel therapeutic strategies to elevate patient suffering, reduce scaring and eliminate chronic wounds. Following the global trend towards automation, miniaturization and integration of cell-based assays into microphysiological systems, conventional wound healing assays such as the scratch assay or cell exclusion assay have recently been translated and improved using microfluidics and lab-on-a-chip technologies. These miniaturized cell analysis systems allow precise spatial and temporal control over a range of dynamic microenvironmental factors including shear stress, biochemical and oxygen gradients to create more reliable in vitro models that resemble the in vivo microenvironment of a wound more closely on a molecular, cellular, and tissue level. The current review provides (a) an overview on the main molecular and cellular processes that take place during wound healing, (b) a brief introduction into conventional in vitro wound healing assays, and (c) a perspective on future cutaneous and vascular wound healing research using microfluidic technology.
ARTICLE | doi:10.20944/preprints201810.0667.v1
Online: 29 October 2018 (09:54:28 CET)
Visfatin, a member of the adipokine family, plays an important role in many metabolic and stress responses. The mechanisms underlying the direct therapeutic effects of visfatin on wound healing have not been reported yet. In this study, we examined the effects of visfatin on wound healing in vitro and in vivo. Visfatin enhanced the proliferation and migration of human dermal fibroblasts (HDFs) and keratinocytes, and significantly increased the expression of wound healing-related vascular endothelial growth factor (VEGF) in vitro and in vivo. Treatment of HDFs with visfatin induced activation of both extracellular signal-regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinases 1 and 2 (JNK1/2) in a time-dependent manner. Inhibition of ERK1/2 and JNK1/2 led to a significant decrease in visfatin-induced proliferation and migration of HDFs. Importantly, blocking VEGF with its neutralizing antibodies suppressed the visfatin-induced proliferation and migration of HDFs and human keratinocytes, indicating that visfatin induces the proliferation and migration of HDFs and human keratinocytes via increased VEGF expression. Moreover, visfatin effectively improved wound repair in vivo, which was comparable to the wound healing activity of epidermal growth factor (EGF). Taken together, we demonstrate that visfatin promotes the proliferation and migration of HDFs and human keratinocytes by inducing VEGF expression and can be used as a potential novel therapeutic agent for wound healing.
REVIEW | doi:10.20944/preprints202203.0293.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: extracellular matrix; biosensing; machine learning; wound healing
Online: 22 March 2022 (03:50:47 CET)
Impaired wound healing is a significant financial and medical burden. The synthesis and deposition of extracellular matrix (ECM) in a new wound is a dynamic process that is constantly changing and adapting to the biochemical and biomechanical signaling from the extracellular microenvironments of the wound. This drives either a regenerative or fibrotic and scar-forming healing outcome. Disruptions in ECM deposition, structure, and composition lead to impaired healing in diseased states, such as in diabetes. Valid measures of the principal determinants of successful ECM deposition include bacterial contamination, tissue perfusion, and mechanical injury and strain. These measures are used by wound-care providers to intervene upon the healing wound to steer healing toward a more functional phenotype with improved structural integrity and healing outcomes and to prevent adverse wound developments.In this review, we discuss bioengineering advances in non-invasive detection of biologic and physiologic factors of the healing wound, visualizing and modeling the ECM, and computational tools to efficiently evaluate the complex data acquired from the wounds to prognosticate healing outcomes and intervene effectively. We focus on bioelectronics and biologic interfaces of the sensors and actuators for real time biosensing and actuation. We also discuss high-resolution, advanced imaging techniques, which go beyond traditional confocal and fluorescence microscopy to visualize microscopic details of the composition of the matrix, linearity of collagen, and live tracking of components within the ECM. Computational modeling of the matrix, including partial differential equation datasets as well as machine learning models that can serve as powerful tools for physicians to guide their decision-making process are discussed.
REVIEW | doi:10.20944/preprints202311.0434.v1
Subject: Chemistry And Materials Science, Polymers And Plastics Keywords: natural polysaccharide; composite hydrogel; wound healing; therapeutic agent
Online: 7 November 2023 (11:14:38 CET)
Numerous innovative advancements in dressing technology for wound healing have emerged. Among the various types of wound dressings available, hydrogel dressings, structured with a three-dimensional network and composed of predominantly hydrophilic components, are widely used for wound care due to their remarkable capacity to absorb abundant wound exudate, maintain a moisture environment, provide soothing and cooling effects, and mimic the extracellular matrix. Composite hydrogel dressings, one of the evolved dressings, address the limitations of traditional hydrogel dressings by incorporating additional components, including particles, fibers, fabrics, or foams, within the hydrogels, effectively promoting wound treatment and healing. The added elements enhance the features or add specific functionalities of the dressings, such as sensitivity to external factors, adhesiveness, mechanical strength, control over the release of therapeutic agents, antioxidant and antimicrobial properties, and tissue regeneration behavior. They can be categorized as natural or synthetic based on the origin of the main components of the hydrogel network. This review focuses on recent research on developing natural polysaccharide-based composite hydrogel wound dressings. Their preparation and composition, the reinforcement materials integrated into hydrogels, and therapeutic agents are also explored. Furthermore, their features and the specific types of wounds where applied are discussed as well.
ARTICLE | doi:10.20944/preprints202011.0332.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: photobiomodulation; blue light; LED; wound healing
Online: 12 November 2020 (09:13:12 CET)
In recent years, photobiomodulation (PBM) has been recognized as a physical therapy in wound management. Despite several published research papers, the mechanism underlying photobiomodulation is still not completely understood. The investigation about application of blue light to improve wound healing is a relatively new research area. Tests in selected patients evidenced a stimulation of the healing process in superficial and chronic wounds treated with a blue LED light emitting at 420 nm; a study in animal model pointed out a faster healing process in superficial wound, with an important role of fibroblasts and myofibroblasts. Here we present a study aiming at evidencing the effects of blue light on the proliferation and metabolism in fibroblasts and keratinocytes. Different light doses were used to treat the cells, evidencing inhibitory and stimulatory effects. Electrophysiology was used to investigate the effects on membrane currents, while Raman spectroscopy revealed the mitochondrial Cytochrome C (Cyt C) oxidase dependence on blue light irradiation. In conclusion, we observed that the blue LED light can be used to modulate the activity of human fibroblasts, and the effects in wound healing are particularly evident when studying the fibroblasts and keratinocytes co-cultures.
REVIEW | doi:10.20944/preprints202205.0358.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Wound; Impregnated materials; Nanoparticles; Dermatology
Online: 26 May 2022 (08:51:48 CEST)
Wounds are structural and functional disruptions of the skin that occur because of an accident. Chronic wounds are caused by a breakdown in the finely coordinated cascade of events that occurs during wound healing. Wound healing is a long process that split into at least three continuous and overlapping processes: an inflammatory response, a proliferative phase that leads to tissue repair, and third one is tissue remodeling. Therefore, wound healing studies are extensively studied to develop techniques that can achieve maximum recovery with minimum scar. Several growth hormones and cytokines secreted at the wound site tightly regulate wound healing processes. The traditional approach for wound management has been represented by topical treatments. Metal nanoparticles (e.g., silver, gold, zinc) are increasingly being employed in dermatology due to their favorable effects on wound healing, as well as in treating and preventing bacterial infections. The development of wound dressings materials has now been used to overcome the issues of external environments. The impregnated nanomaterials have provided moist environment that removes the exudates and avoid maceration. This review highlights the mechanism and focus on the current advancement of various nanoparticles impregnation material for wound healing process that can protect wound from infection and maintain the optimum exchange of gases.
REVIEW | doi:10.20944/preprints202209.0354.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Wound healing; metastasis; oxidative stress; macrophage; HIF; NF-kB; Nrf2
Online: 23 September 2022 (03:28:28 CEST)
Many signaling pathways, molecular and cellular actors which are critical for wound healing have been implicated in cancer metastasis. These two conditions are a complex succession of cellular biological events and accurate regulation of these events is essential. Apart from inflammation, macrophages-released ROS arise as major regulators of these processes. But, whatever the pathology concerned, oxidative stress is a complicated phenomenon to control and requires a finely tuned balance over the different stages and responding cells. This review provides an overview of the pivotal role of oxidative stress in both wound healing and metastasis, encompassing the contribution of macrophages. Indeed, macrophages are major ROS producers but also appear as their targets since ROS interfere with their differentiation and function. Elucidating ROS functions in wound healing and metastatic spread may allow the development of innovative therapeutic strategies involving redox modulators.
REVIEW | doi:10.20944/preprints202108.0004.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: extracellular vesicles; EVs; exosomes; mesenchymal stem cell EVs; plant-derived EVs; wound healing; scaffolds
Online: 2 August 2021 (08:57:45 CEST)
Each year, millions of individuals suffer from a non-healing wound, abnormal scarring, or injuries accompanied by an infection. For these cases, scientists are searching for new therapeutic interventions, from which one of the most promising is the use of extracellular vesicles (EVs). Naturally, EV-based signalling takes part in all four wound healing phases: hemostasis, inflammation, proliferation and remodelling. Such an extensive involvement of EVs suggests exploiting their action to modulate the impaired healing phase. Furthermore, next to their natural wound healing capacity, EVs can be engineered for better defined pharmaceutical purposes, such as carrying specific cargo or targeting specific destinations by labelling them with certain surface proteins. This review aims to promote scientific awareness in basic and translational research of EVs by summarizing the current knowledge about their natural role in each stage of skin repair and the most recent findings in application areas, such as wound healing, skin regeneration and treatment of dermal diseases, including the stem cell-derived, plant-derived and engineered EVs.
REVIEW | doi:10.20944/preprints202303.0054.v1
Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: natural products; wound healing; phytomolecules; cytotocxic; curcumin
Online: 3 March 2023 (03:37:50 CET)
Wound healing is a process through which skin maintains itself. Once a wound occurs, the inflammatory and proliferative stages are instigated in reaction to injury. It is established that wound restorative comprises four stages including haemostasis, inflammation, proliferation, and remodeling. The amelioration of wound healing is very challenging as tumors can develop at the site of chronic injury. There are numerous plants, plant extracts and plant based natural products were widely used by tribal communities from ancient times for the treatment of cuts, burns, scars, burns and wounds. The therapeutic potential of these plants is recognized due to the presence of phytomolecules such as phenolic compounds, flavonoids, triterpenoids, saponins, tannins, alkaloids and glycosides. The plant used for the treatments of wound healing includes Achillea millefolium, Andrographis paniculata, Boswellia sacra, Calendula officinalis, Crocus sativus, Curcuma longa, Ehretia laevis, Ehretia microphylla, Glycyrrhiza glabra, Malva sylvestris, Rosmarinus officinalis and Salvia officinalis. This assemblage comprises the structures of phytomolecules isolated from the different extracts of these plants, mechanistic insights and important key findings responsible for wound healing. The mechanistic insights involved in wound healing are similar to cytotoxic, anti-inflammatory and antioxidant agents such as ROS generation, DNA fragmentation and western blotting. This review article is an effort to bridge the gaps in the prevailing literature and thus offers gigantic scope for researchers and academicians betrothed in validation of the customary claims and development of safer and efficient and worldwide recognized natural potential candidates as drugs for healing of wounds, burns and cuts.
ARTICLE | doi:10.20944/preprints202011.0218.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: Ferroelectrics; Composite; Membranes; Wound healing
Online: 5 November 2020 (15:02:01 CET)
Herein, we report results of the study of the composite ferroelectric scaffolds based on vinylidene fluoride-tetrafluoroethylene copolymer (VDF-TeFE) and polyvinylpyrrolidone (PVP) produced by electrospinning and their application as a wound-healing material. The physicochemical properties of ferroelectric composite polymer scaffolds depending on the content of PVP (in the range from 0 to 50 wt %) including morphology, composition and crystalline structure were studied. The cytotoxicity of materials and the proliferative activity of cells during their cultivation on the surface of formed scaffolds are reported. It has been found that the optimal PVP content in the VDF-TeFE composite scaffolds is 15 wt%. On a model of a full-thickness contaminated wound in vivo, it was shown that piezoelectric scaffolds based on VDF-TeFE copolymer containing 15 wt% PVP provide better wound healing results in comparison with standard gauze dressings impregnated with a solution of an antibacterial agent.
REVIEW | doi:10.20944/preprints202306.0211.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: biomaterials; decellularization; extracellular matrix; placenta; placental-derived biomaterials; wound healing
Online: 2 June 2023 (14:14:07 CEST)
Chronic wounds are associated with considerable patient morbidity and present a significant economic burden to the healthcare system. Often, chronic wounds are in a state of persistent in-flammation and unable to progress to the next phase of wound healing. Placental-derived bio-materials are recognized for their biocompatibility, biodegradability, angiogenic, an-ti-inflammatory, anti-microbial, anti-fibrotic, immunomodulatory, and immune privileged prop-erties. As such, placental-derived biomaterials have been used in wound management for more than a century. Placental-derived scaffolds are composed of an extracellular matrix (ECM) that can mimic the native tissue, creating a reparative environment to promote ECM remodeling, cell migration, proliferation, and differentiation. Reliable evidence exists throughout the literature to support the safety and effectiveness of placental-derived biomaterials in wound healing. How-ever, differences in source (i.e., anatomical regions of the placenta), preservation techniques, decellularization status, design, and clinical application have not been fully evaluated. This re-view provides an overview of wound healing and placental-derived biomaterials, summarizes the clinical results of placental-derived scaffolds in wound healing, and suggests directions for future work.
REVIEW | doi:10.20944/preprints202107.0361.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: wound healing; oxidative stress; antioxidant dressing; reactive oxygen species.
Online: 15 July 2021 (13:32:15 CEST)
(1) Background: Reactive oxygen species (ROS) play a crucial role in the preparation of the normal wound healing response. Therefore, a correct balance between low or high levels of ROS is essential. Antioxidant dressings that regulate this balance is a target for new therapies. The purpose of this review is to identify the compounds with antioxidant properties that have been tested for wound healing and to summarize the available evidence on their effects. (2) Methods: A literature search was conducted and included any study that evaluated the effects or mechanisms of antioxidants in the healing process (in vitro, animal models, or human studies). (3) Results: Seven compounds with antioxidant activity were identified (Curcumin, N-acetyl cysteine, Chitosan, Gallic Acid, Edaravone, Crocin, Safranal, and Quercetin) and 46 studies reporting the effects on the healing process of these antioxidants compounds were included. (4) Conclusions: These results highlight that numerous novel investigations are being conducted to develop more efficient systems for wound healing activity. The application of antioxidants is useful against oxidative damage and accelerates wound healing. Designing biomaterials that can scavenge excess reactive oxygen species requires new technologies and further research, especially human studies.
BRIEF REPORT | doi:10.20944/preprints202209.0409.v1
Subject: Medicine And Pharmacology, Dentistry And Oral Surgery Keywords: chlorhexidine; bioactive liquid; oral wound healing; pain index score; early wound healing score
Online: 27 September 2022 (03:37:27 CEST)
After surgery, oral cavity healing occurs in a hostile environment and requires proper oral care and hygiene to accelerate recovery. The aim of the current study is to investigate and compare the bioreactivity characteristics of chlorhexidine based (CHX) mouth rinse and a novel bone bioactive liquid (BBL) mouth rinse on oral healing within seven days application post-surgery. A randomized, double blind clinical trial conducted in 81 patients. The mouth rinses were applied twice a day for a period of 7 days. The visual analog scale (VAS) protocol was applied to measure pain index. Early wound healing score (EHI) was determined in evaluate the oral cavity healing progress. No adverse effects were observed using the mouth washes, but CHX resulted in teeth staining. CHX and BBL were sufficient to reduce pain over a period of 7 days. However, the BBL group demonstrated a statistically significant reduction in VAS stating day 4. Relative to CHX group, the EHI scores were significantly higher in the BBL group, independent from the tooth location. No gender differences were observed in both VAS and EHI scores. Relative to the commercially available CHX, BBL mouth rinse reduced pain and accelerated oral cavity healing. Suggesting an improvements of oral cavity microenvironment at the wound site that mediates soft tissue regeneration.
ARTICLE | doi:10.20944/preprints202304.0286.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: graphene oxide; nanocellulose; reduced graphene oxide; polydopamine; wound healing
Online: 13 April 2023 (03:21:21 CEST)
Plant extracts have been evaluated to determine their bioactivities and their potential use in wound healing. In this study, a conductive composite material, based on graphene oxide (GO), nanocellulose (CNF) and tannins (TA) from pine bark, reduced using polydopamine (PDA), was developed for wound dressing. The amount of CNF and TA was varied in the composite material and a complete characterization including SEM, FTIR, XRD, XPS, TGA was performed. Also, the conductivity, mechanical properties, cytotoxicity, and in vitro wound healing of the materials were evaluated. The results showed a successful physical interaction between CNF, TA and GO. In-creasing the CNF amount in the composite reduced the thermal properties, surface charge and conductivity of the material, but its strength, cytotoxicity and wound healing performance were improved. The TA incorporation slightly reduced the cell viability and migration, which may be associated with the doses used and the chemical composition of the extracts. However, the in vitro obtained results demonstrated that these composite materials can be suitable for wound healing.
REVIEW | doi:10.20944/preprints202306.0851.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: wound healing; probiotics; lactoplantibacillus plantarum; lactobacillus rhamnosus; lactobacillus acidophilus; Bifidobacterium longum; lactobacillus casei; lactobacillus reuteri; lactobacillus refmentum
Online: 12 June 2023 (14:46:07 CEST)
Wound healing is a multi-factorial response to tissue injury, aiming to restore tissue continuity. Numerous recent experimental and some clinical studies, clearly indicate that probiotics applied topically promote the wound healing process. However, the precise mechanism by which they contribute to healing is not yet clear. Each strain appears to exert a distinctive, even multi-factorial action on different phases of the healing process. Given that a multi-probiotic formula exerts better results than a single strain, the pharmaceutical industry has embarked on a race for the production of a formulation containing a combination of probiotics, capable of playing a role in all the phases of the healing process. Hence, the object of this review is to describe what is known to date of the distinctive mechanisms of each of the most studied probiotic strains in order to further facilitate research towards the development of combinations of strains and doses, covering the whole spectrum of healing. Eleven probiotic species have been analyzed, the only criterion of inclusion being a minimum of two published research articles.
ARTICLE | doi:10.20944/preprints202106.0374.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Mesenchymal Stem Cells 1; Cell Migration 2; Xenogeneic Wound Repair 3.
Online: 14 June 2021 (15:06:48 CEST)
Bone marrow derived adult human mesenchymal stem cells (hMSCs) possess therapeutic qualities that enable them to enhance wound repair. However, the mechanisms by which this occurs remains poorly understood. Basic mechanisms may include the directed migration of delivered cells to target sites and/or the production and release of soluble factors that act at a distance. Allogeneic and even xenogeneic cells may effectively participate in wound repair. Labeled hMSCs were delivered to full-thickness skin wounds that were created in immunologically competent mice. The delivery occurred on day 3 post-wounding using two different carriers; one which released cells and one which retained cells. The fates of the delivered cells were tracked for up to 25 days. During this period, released cells migrated as a tight cohort deep into the wound to reach the subdermal vascular plexus. Simultaneously, enhanced formation of granulation tissue was evident. This migration of hMSCs was not essential in that enhanced granulation tissue formation and wound contraction occurred when cells were retained in the carrier matrix. This provided further evidence for the release of therapeutic factors by hMSCs to sites of injury.
ARTICLE | doi:10.20944/preprints202308.0150.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: nanoemulsion; wound healing effect; essential oil
Online: 2 August 2023 (08:29:35 CEST)
This study develops an efficient, low-temperature process for formulating a nanoemulsion-based gel encapsulating Pituranthos tortuosus's essential oil, investigating its wound healing potential. The novel process ensured stable encapsulation of the medicinal plant's oil. The nanoemulsion was characterized using dynamic light scattering and transmission electron microscopy, followed by in vitro and in vivo tests to examine wound healing efficacy. Results revealed the gel's excellent stability, high encapsulation efficiency, and significant wound-healing effects. This research provides a new method for formulating Pituranthos tortuosus's essential oil nanoemulsion-based gel, emphasizing the potential role of plant-based therapies in healthcare advancement, and invites further exploration into the therapeutic applications of essential oil-encapsulating nanoemulsions.
ARTICLE | doi:10.20944/preprints201806.0334.v2
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: hepatic injury; sealants; metalloproteinases; inflammatory response; wound healing
Online: 27 June 2018 (10:43:43 CEST)
. Sealants and adhesives are used in the repair and preservation of damaged solid organs. This study examines the matrix metalloproteinases (MMP) activity in the healing of liver injuries treated with two biological adhesives (Tachosil® and GelitaSpon®) as well as that of a new elastic cyanoacrylate (Adhflex®). Methods. We induced in 90 male rats hepatic lesions using a Stiefel biopsy punch in the liver. Wound healing was assessed 2, 6, and 18 days after injury by quantifying MMP1, 2, 8, 9, and 13 tissue levels. The histopathological repair was evaluated by hematoxylin-eosin, Masson’s trichrome, and Periodic Acid Schiff (PAS) staining and CD31, CD68 immunohistochemical marker. The three sealants used contributed to the complete healing of hepatic lesions. Both histopathology and MMP findings point to the fact that degradation with Adhflex® is slower and causes a strong inflammatory reaction at the onset of healing. Results. All the MMPs measured showed higher values early in the healing process in animals treated with Adhflex® and Tachosil, expression for MMP2 and MMP9 being significantly higher in the Adhflex-treated group. Animals treated with Tachosil had significant greater values of MMP8 and MPP13 than the Adhflex group. Animals treated with Adhflex® showed a sustained overexpression in all MMPs even at the latest wound healing stages. Conclusion. Notably, the overexpression of the MMPs did not negatively influence the histological healing process of liver injuries. Since all hepatic trauma injuries should be treated as emergencies, any easy-to-use and rapid sealant, like Adhflex®, could be considered an adequate treatment option.
ARTICLE | doi:10.20944/preprints201804.0262.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: hepatic injury; sealants; metalloproteinases; inflammatory response; wound healing
Online: 20 April 2018 (11:14:49 CEST)
Background. Adhesives and sealants can be used to repair and preserve solid damaged organs. This study explores the activity of different matrix metalloproteinases (MMP) during the healing of liver injuries treated with two biological adhesives (Tachosil and GelitaSpon) and a new synthetic elastic cyanoacrylate (Adhflex®). Methods. Liver traumatic injuries were experimentally induced in 90 male Wistar rats using a Stiefel biopsy punch in the liver. Wound healing was evaluated 2, 6, and 18 days after injury by determining MMP1, 2, 8, 9, and 13 expression. The histopathological repair was assessed by hematoxylin-eosin, Masson’s trichrome, and Periodic Acid Schiff (PAS) staining. The three sealants used supported complete healing of the liver lesions. Both histopathology and MMP findings indicate that the degradation process of Adhflex® is slower and produces a strong initial inflammatory reaction. Results. All the MMPs measured disclosed higher values at early stage of the healing process in animals treated with Adhflex® and Tachosil, being the expression of for MMP2 and MMP9 significantly higher in the Adhflex-treated group. Animals treated with Tachosil had significant higher values of MMP8 and MPP13 than the Adhflex-treated group. Animals treated with Adhflex® showed a maintained overexpression in all the MMPs tested even at the latest wound healing stages. Conclusion. Notably, this MMPs overexpression did not influence negatively the histological healing process of the hepatic injuries. Given that all hepatic trauma injuries should be considered emergencies, any easy-to-use and rapid sealant, such as Adhflex®, could be considered as a suitable treatment option.
ARTICLE | doi:10.20944/preprints202202.0108.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: 3D printing technology; freshwater turtle; Ocadia Spp.; shell wound healing
Online: 8 February 2022 (12:22:31 CET)
Numerous cases and a shortage of resources usually limit wild animal rescue. New technology implemented might save these severely injured wild animals from the situation of euthanasia by easing the requirement of intensive medication. Three-dimensional (3D) technologies provide precise and accurate results that improve the quality of the medical application. These 3D tools have become relatively low-cost and accessible in the past years. In the medical field of exotic animal, turtle shell defect is highly challenging because of inevitable water immersion. This report is the first attempt to apply the combination of 3D scanning, computer-aid design (CAD), and 3D printing to make a protective device that frees the wound from exposure to water or infection sources. The presenting techniques successfully extricate a wild freshwater turtle from an extensive shell defect within a short period. Integration of multiple sciences to 3D technology can provide a facile model for veterinary medical applications.
REVIEW | doi:10.20944/preprints202306.1736.v1
Subject: Medicine And Pharmacology, Other Keywords: animal models; exosomes; skin regeneration; wound healing; systematic review.
Online: 26 June 2023 (04:55:12 CEST)
Exosomes have shown promising potential as a therapeutic approach for wound healing. Nevertheless, the translation from experimental studies to commercially available treatments is still lacking. To assess the current state of research in this field, a systematic review was performed to examine the methodological heterogeneity among studies conducted over the past five years. Additionally, the review analyzed the suitability of animal models used and their relevance to human medicine. A PubMed search was performed for english-language, full-text available papers published from 2018 to June 2023, focusing on exosomes derived from mammalian sources and their application in wound healing, particularly those involving in vivo assays. Out of 531 results, 148 papers were selected for analysis. The findings revealed significant variability in terms of cell sources and types, biomaterials, and administration routes under investigation, indicating the need for further research in this field. Additionally, a comparative examination encompassing diverse cellular origins, types, administration pathways, or biomaterials is imperative. Furthermore, the predominance of rodent-based animal models raises concerns, as there have been limited advancements towards more complex in vivo models and scale-up assays. These constraints underscore the substantial efforts that remain necessary before attaining commercially viable and extensively applicable therapeutic approaches using exosomes.
ARTICLE | doi:10.20944/preprints202302.0314.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: Electrospinning; Nanofibers; Polycaprolactone; Plantago Major L; Drug delivery; Wound dressing
Online: 20 February 2023 (01:32:00 CET)
Plantago major L. is a worldwide available plant that has been used traditionally for several medical application due to its properties such as wound healing, anti-inflammatory, antimicrobial etc. This work aimed to develop and evaluate nanostructured PCL electrospun dressing with P. major extract encapsulated in nanofibers for application in wound healing. The extract from leaves was obtained by extraction in a mixture of water:ethanol= 1:1 of the freeze-dried extract presented a minimum inhibitory concentration (MIC) for Staphylococcus Aureus susceptible and resistant to methicillin of 5.3 mg/mL, a high antioxidant capacity, but a low content of total flavonoids. Electrospun mats without defects were successfully produced using two P. major extract concentrations based on MIC value. The extract incorporation in PCL nanofibers was confirmed by FTIR and contact angle measurements. The PCL/P. major extract was evaluated by DSC and TGA demonstrating that incorporation of the extract decreases the thermal stability of the mats as well as the degree of crystallinity of PCL-based fibers. The P. major extract incorporation on electrospun mats produced a significant swelling degree (more than 400%) and increased the capacity of adsorbing wound exudates and moisture, important characteristics for skin healing. The extract-controlled release evaluated by in vitro study in PBS (pH, 7.4) shows that P. major extract delivery from the mats occurs in the first 24 h, demonstrating their potential capacity to be used in wound healing.
ARTICLE | doi:10.20944/preprints202305.1466.v1
Subject: Medicine And Pharmacology, Pharmacy Keywords: Lawsonia inermis; Henna; leaves; phytochemical; wound healing activity; Morocco
Online: 22 May 2023 (05:30:59 CEST)
The present study aims at valorizing Moroccan Henna (Lawsonia inermis) by developing healing formulations for cosmetic and therapeutic uses. For such a goal, the plant was collected from three locations in Southeastern Morocco (Alnif, Tafraoute Sidi Ali and Tazarine). Phytochemical anal-yses of aqueous extracts of Henna leaves was performed by determining phenolic compounds contents, flavonoids and tannins in the extracts. Then, specific formulations were prepared using aqueous extracts of L. inermis to assess their in vivo wound healing potential in Swiss Albino mice as animal model. Results disclosed that phenolic compound contents (13.48%), flavonoids (9.25%) and tannins (2.57%) are higher in Henna leaf extracts from Alnif, while Tazarine Henna aqueous extract was found to be richer in saponins (0.32%). Exclusion chromatographic analysis on Se-phadex G50 gel corroborates the obtained results and shows that Lawsone levels (Henna coloring agent) are higher in Henna collected from Alnif. Aqueous Henna leaf extracts, at a dose of 10% in petroleum jelly, have been tested for their ability to heal induced burns in mice. Healing moni-toring, carried out with Henna extracts on mice batches and those of two control batches (Mice batch treated with petroleum jelly alone and batch treated with petroleum jelly containing 1% flamazine), showed a great reduction in burnt surface with an accentuated contraction percentage (CP) and complete re-epithelialization duration (CRD) at 21 days in the three studied Henna-based formulations. These findings suggest the interest of potential development of Henna-based for-mulations, as source of phenolic compounds, for further dermatological, cosmetic and therapeutic applications.
ARTICLE | doi:10.20944/preprints201812.0192.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: hepatic injury; sealants; metalloproteinases; inflammatory response; wound healing
Online: 17 December 2018 (10:52:27 CET)
This study examines the matrix metalloproteinase (MMP) activity in the healing of liver injuries treated with biological adhesives Tachosil® and GelitaSpon® and the elastic cyanoacrylate Adhflex®. Hepatic lesions were induced in male rats using a Stiefel biopsy punch. Healing was assessed 2, 6, and 18 days after injury by quantifying tissue levels of MMP1, 2, 8, 9, and 13. Histopathological repair was evaluated using hematoxylin-eosin, Masson’s trichrome, and Periodic Acid Schiff (PAS) staining and immunohistochemical markers CD31 and CD68. The sealants contributed to complete healing. Histopathology and MMP findings indicate that Adhflex® has slower degradation and a strong inflammatory reaction at the onset of healing. Early on, all MMPs showed higher levels in Adhflex® and Tachosil®-treated animals, and MMP2 and MMP9 expressions were significantly higher in the Adhflex-treated group at 18 days post-injury (T3). The Adhflex® group had significantly higher MMP8 and MPP13 levels than other treated groups and showed a sustained overexpression of all MMPs, even in the latest healing stages. Notably, the overexpression did not negatively influence the histological healing process. All hepatic trauma injuries should be treated as emergencies, and any easy-to-use and rapid sealant like Adhflex® could be considered as an option for treating liver trauma.
ARTICLE | doi:10.20944/preprints201911.0171.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: ulmus parvifolia; wound healing; matrix metalloproteinase; transforming growth factor; skin rejuvernation
Online: 15 November 2019 (04:05:45 CET)
Ulmus species have been widely used in Korean folk medicine because of their anti-inflammatory and antimicrobial properties. We intended to investigate the wound healing effect of the powder of Ulmus parvifolia (UP) root bark in a mouse wound healing model. We also determined the mechanisms of effects of Ulmus parvifolia (UP) in skin and skin wound healing effect using keratinocyte model. in vivo experiments showed that the wound lesions in the mice decreased by U. parvifolia with 200 mesh size of root bark powder and significantly reduced by treatment with UP, compared with those treated with U. macrocarpa (UM). Results from in vitro experiments also revealed that UP extract promoted the migration of human skin keratinocytes. UP powder treatment upregulated the expression of the matrix metalloproteinase-2 and -9 protein and significantly increased transforming growth factor (TGF)-β levels. We confirmed that topical administration of the bark powder of exerted a significant effect on skin wound healing by upregulating the expression of MMP and transforming growth factor-β. TGF-β In, Our study suggests that U. parvifolia may be a potential candidate for skin wound healing including epidermal skin rejuvernation.
ARTICLE | doi:10.20944/preprints202308.0512.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: PLLA nanosheets; laser ablation in liquid; Fe-containing nanoparticles; metal-ion release; burn wound healing
Online: 7 August 2023 (10:49:10 CEST)
: This article reports on polymer (PLLA, poly(L-lactic acid)) nanosheets incorporated with Fe-ion nanoparticles, aiming at using the latter nanoparticles as source to release Fe ions to facilitate burn wound healing when such nanosheets are applied on skin as biomedical tissue. Laser ablation in liquid phase was used to produce Fe-containing nanoparticles that after incorporation into PLLA nanosheets would release Fe ions when in immersed in water. Such nanoparticles prepared in chloroform are shown by XPS to be based on iron chloride and oxide phases. After incorporation into PLLA nanosheets, the ion –release test demonstrated that Fe ions could be released successfully into water at pH 7.4, which implies that such polymer nanosheets show promise for biomedical applications as potential patches for healing burn wounds. Incorporation with two different metal ions (Fe and Zn) is shown to be efficient and both types of ions were demonstrated to be released simultaneously and with comparable release rates.
REVIEW | doi:10.20944/preprints202012.0029.v1
Subject: Chemistry And Materials Science, Nanotechnology Keywords: drug delivery; immune response; inflammation; critical solution temperature; scaffolds; smart polymers; tissue engineering; thermo-responsive; wound healing.
Online: 1 December 2020 (13:55:35 CET)
innate and adaptive immune responses lead to wound healing by regulating a complex series of events promoting cellular cross-talk. An inflammatory response is presented with its characteristic clinical symptoms: heat, pain, redness, and swelling. Some smart thermo-responsive polymers like chitosan can be used to create biocompatible and biodegradable scaffolds with 3D architectures similar to human structures, allowing their efficient and safe use as tissue engineering and drug delivery systems in chronic wounds. Locally heated tumors above polymer lower critical solution temperature can induce its conversion into a hydrophobic form, enhancing drug release until the thermal stimulus is gone, where a lower release is due to the swelling of the material. This paper integrates the relevant reported contributions of bioengineered scaffolds for thermo-responsive drug delivery in wound healing. Therefore, we present a comprehensive review that aims to demonstrate the capacity of these systems to provide spatially and temporally controlled release strategies for one or more drugs used in wound healing. In this sense, the novel manufacturing techniques of 3D-printing and electrospinning are explored for the tuning of their physicochemical properties to adjust therapies according to the patient’s convenience, as well as reduce drug toxicity and side effects.
ARTICLE | doi:10.20944/preprints202307.0626.v1
Subject: Medicine And Pharmacology, Veterinary Medicine Keywords: Animal wound; Anti-biofilm forming; Antimicrobial activities; Skin microflora; Titanium dioxide
Online: 11 July 2023 (03:08:32 CEST)
The use of metal oxide nanoparticles as an alternative antimicrobial agent has gained attention due to the increasing problem of antibiotic resistance. Understanding its properties and potential benefits can contribute to the development of more effective and sustainable treatments in veterinary medicine. The aim of this study was to characterize TiO2-NP formulations and evaluate their antibacterial and wound healing abilities. The diameters and zeta potentials were determined using the Zetasizer in conjunction with dynamic light scattering. The agar-well diffusion method, time-kill kinetic assay and crystal violet assay were used to evaluate their antimicrobial activities. Wound healing assays were conducted both in-vitro and in-vivo. The study demonstrated that TiO2-NP formulations exhibit significant antimicrobial properties against various bacterial strains such as S. aureus and E. coli. No measurable E. coli growth was observed within a 15-mins period following exposure to TiO2-NP formulations. The TiO2-NP formation can improve wound healing by enhancing cell migration and collagen formation in both in-vitro and in-vivo conditions. In summary, our study suggests that TiO2-NP has the potential for use as an antimicrobial agent for animal wound treatment due to its ability to suppress bacterial growth and biofilm formation, as well as to enhance wound healing.
ARTICLE | doi:10.20944/preprints202209.0026.v1
Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: Bacopa procumbens HPLC characterization; effect of polyphenolic compounds; in vitro and in vivo skin wound; collagen organization
Online: 1 September 2022 (15:44:09 CEST)
Wounds represents a medical problem that contribute importantly to patient morbidity and to the healthcare costs in several pathologies. In Hidalgo, Mexico, Bacopa procumbens plant has been traditionally used for wound healing care for several generations; in vitro and in vivo experiments were design to evaluate the effects of bioactive compounds obtained from B. procumbens aquoethanolic extract and to determine the key pathways involved in wound regeneration. Bioactive compounds were characterized by HPLC- QTOF-MS and proliferation, migration, adhesion, and differentiation studies were done on NIH/3T3 fibroblasts. Polyphenolic compounds from Bacopa procumbens (PB) regulated proliferation and cell adhesion; enhanced migration reducing the artificial scratch area; and modulated cell differentiation. PB compounds were included in a hydrogel for topical administration on rat excision wound model. Histological, histochemical and mechanical analysis showed that PB treatment accelerates wound closure in at least 48 h; reduce inflammation, increasing cell proliferation and deposition and organization of collagen in earlier times. These changes resulted in the formation of a scar with better tensile properties. Immunohistochemistry and RT-PCR molecular analyses demonstrated that treatment induces: i) overexpression of transforming growth factor beta (TGF-β); and ii) the phosphorylation of Smad 2/3 and ERK1/2, suggesting the central role of some PB to enhance wound healing, modulating TGF-β activation.
ARTICLE | doi:10.20944/preprints202310.0811.v1
Subject: Chemistry And Materials Science, Applied Chemistry Keywords: k-carrageenan, acrylamide, cetrimide, antimicrobial, anti-inflammatory, wound healing
Online: 12 October 2023 (11:25:30 CEST)
The current study aims to produce a material that has a dual effect of healing and anti-inflammatory. For this target k-carrageenan/polyacrylamide hydrogel film loaded with cetrimide (k-CAR/PAAm/CI) was performed by manual casting technique. Definite concentrations of k-CAR and AAm was heated at 80°C for 2 hours, CI and glycerol were added. The solution was cast without using initiator and cross-linker. The reaction of the sulfonic acid group -SO3H of k-CAR with -CONH2 group of PAAm lead to the formation of a sulfonamide (-SO2NH-) linkage. The characteristics of the produced films were investigated by FTIR, TGA, contact angle, and mechanical properties. Improvement in the thermal stability was performed in k-CAR/PAAm/CI2 film containing 1.5% CI compared to the film has 0.5% CI (k-CAR/PAAm/CI1). The contact angle measurement proved the films are hydrophobic that enhanced by increasing CI content. The tensile strength and elongation percent values are considered adequate for materials used in wound care. k-CAR/PAAm/CI2 (1.5% CI) film showed superior antimicrobial activity against P. aeruginosa, moderate activity against S. aureus, and low activity against E. coli. The film k-CAR/PAAm/CI2 was effectively inhibiting the heat-induced hemolysis and may offer a promising approach for the development of effective wound dressings.
REVIEW | doi:10.20944/preprints202306.1202.v1
Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: Astrogliosis; Brain endothelial cells; Enlarged perivascular spaces; Microgliosis; Perivascular macrophages; Wound Healing
Online: 16 June 2023 (10:04:27 CEST)
Embryonic genetic mechanisms are present in the brain and ready to be placed into action upon cellular injury termed the response to injury wound healing (RTIWH) mechanism. When injured, regional brain endothelial cells initially undergo activation and dysfunction with initiation of hemostasis, inflammation (peripheral leukocytes and innate microglia and perivascular macrophage cells), proliferation (astrogliosis), remodeling, repair, and resolution phases if the injurious stimuli are removed. In conditions wherein the injurious stimuli are chronic as occurs in obesity, metabolic syndrome, and type 2 diabetes mellitus this process does not undergo resolution and there is persistent RTIWH with remodeling. Indeed, the brain is unique, in that it utilizes its neuroglia: the microglia cell along with peripheral inflammatory cells and its astroglia instead of peripheral scar-forming fibrocytes/fibroblasts. The brain undergoes astrogliosis to form a gliosis scar instead of a fibrosis scar to protect the surrounding neuropil from regional parenchymal injury. One of the unique and evolving remodeling changes in the brain is the development of enlarged perivascular spaces (EPVS), which is the focus of this brief review. EPVS are important since they serve as a biomarker for cerebral small vessel disease and also represent an impairment of the effluxing glymphatic system that is important for the clearance of metabolic waste from the interstitial fluid to the cerebrospinal fluid and disposal. Therefore, it is important to better understand how the RTIWH mechanism is involved in the development of EPVS that are closely associated with and important to the development of premature and age-related cerebrovascular and neurodegenerative diseases with impaired cognition.
REVIEW | doi:10.20944/preprints201812.0170.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: bacterial nanocellulose; nanofibrillated nanocellulose; animal nanocellulose; algal nanocellulose; tissue engineering; tissue repair; wound dressing; cell delivery; drug delivery; antimicrobial properties
Online: 14 December 2018 (06:44:53 CET)
Nanocellulose is cellulose in the form of nanostructures, i.e. features not exceeding 100 nm at least in one dimension. These nanostructures include nanofibrils, e.g. in bacterial cellulose; nanofibers, e.g. in electrospun matrices; nanowhiskers and nanocrystals. These structures can be further assembled into bigger 2D and 3D nano-, micro- and macro-structures, such as nanoplatelets, membranes, films, microparticles and porous macroscopic matrices. There are four main sources of nanocellulose: bacteria (Gluonacetobacter), plants (trees, shrubs, herbs), algae (Cladophora) and animals (Tunicata). Nanocellulose has emerged for a wide range of industrial, technology and biomedical applications, e.g. for adsorption, ultrafiltration, packaging, conservation of historical artifacts, thermal insulation and fire retardation, energy extraction and storage, acoustics, sensorics, controlled drug delivery, and particularly for tissue engineering. Nanocellulose is promising for use in scaffolds for engineering of blood vessels, neural tissue, bone, cartilage, liver, adipose tissue, urethra and dura mater, for repairing connective tissue and congenital heart defects, and for constructing contact lenses and protective barriers. This review is focused on applications of nanocellulose in skin tissue engineering and wound healing as a scaffold for cell growth, for delivering cells into wounds, and as a material for advanced wound dressings coupled with drug delivery, transparency and sensorics. Potential cytotoxicity and immunogenicity of nanocellulose are also discussed.
ARTICLE | doi:10.20944/preprints202309.1022.v1
Subject: Medicine And Pharmacology, Dentistry And Oral Surgery Keywords: dental laser systems; low level laser theraphy; pediatric dentistry; photobiomodulation; wound healing
Online: 15 September 2023 (08:31:52 CEST)
Background:This study evaluated the effect of low-level laser therapy on postoperative pain and wound healing in children undergoing primary molar extractions.Methods:40children,6-10years of age, systemically healthy, and had atraumatic extraction indications of bilateral primary molar teeth were included in the study. First session randomly selected tooth was extracted under local anesthesia. In the control group, only the clot formation on the socket was observed and photographed. Other group extraction's performed 2weeks later. The LLLT group treated with980nm wavelength Doctor Smile Wiser diode laser and photographed. Non-epithelialized surface measurements performed with the ImageJ program. Pain assessment was performed with Wong-Baker Pain Scale. Statistical analyzes were performed with SPSS software.Results: There was no statistically significant difference in Wong-Baker values(p>0.05). The laser group had more '0' values on days 1 and7; same values as the control group were recorded on other days. In soft tissue healing 3rd day evaluations, non-epithelialized surface of laser socket was found to be smaller than control group, and measurement results were found to be statistically significant(p<0.05). The other days' measurement results were not statistically significant(p>0.05).Conclusions:Although LLLT not found to be very effective in reducing postoperative discomfort after extraction of primary molars, it provides better wound healing in extraction sockets.
COMMUNICATION | doi:10.20944/preprints202305.0357.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: ABCB5; cell therapy; mesenchymal stromal cells; recessive dystrophic epidermolysis bullosa; wound healing
Online: 5 May 2023 (10:49:57 CEST)
Recessive dystrophic epidermolysis (RDEB) is a rare, inherited and currently incurable skin blistering disorder characterized by cyclically recurring wounds coexisting with chronic non-healing wounds. In a recent clinical trial three intravenous infusions of skin-derived ABCB5+ mesenchymal stromal cells (MSCs) to 14 patients with RDEB improved healing of wounds that were present at baseline. Since in RDEB even minor mechanical forces perpetually provoke the development of new or recurrent wounds, a post-hoc analysis of patient photographs was performed to specifically assess the effects of ABCB5+ MSCs on new or recurrent wounds by evaluating 174 wounds that occurred after baseline. During 12 weeks of systemic treatment with ABCB5+ MSCs the number of newly occurring wounds declined. When compared to the previously reported healing responses of the wounds present at baseline, the newly occurring wounds healed faster, and a greater portion of healed wounds remained stably closed. These data suggest a previously undescribed skin-stabilizing effect of treatment with ABCB5+ MSCs and support repeated dosing of ABCB5+ MSCs in RDEB to continuously slow the wound development and accelerate the healing of new or recurrent wounds before they become infected or progress to a chronic, difficult-to-heal stage.
COMMUNICATION | doi:10.20944/preprints202308.0124.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: amniotic membrane stem cell; exosome-rich conditioned medium (ERCM); growth factor; neurotrophic factor; wound healing; keratinocyte proliferation; collagen synthesis
Online: 2 August 2023 (07:32:13 CEST)
Tissue regeneration is an essential requirement for wound healing and recovery of organs’ dysfunction. It has been demonstrated that wound healing can be facilitated by activating paracrine signaling mediated by exosomes secreted from stem cells, since exosomes deliver many functional molecules including growth factors (GFs) and neurotrophic factors (NFs) effective for tissue regeneration. In this study, an exosome-rich conditioned medium (ERCM) was collected from human amniotic membrane stem cells (AMSCs) by cultivating the cells under a low oxygen tension (2% O2 and 5% CO2). The contents of GFs and NFs including keratinocyte growth factor, epidermal growth factor, fibroblast growth factor 1, transforming growth factor-β, and vascular endothelial growth factor responsible for skin regeneration were much higher (10-30 folds) in the ERCM than in normal conditioned medium. In was found that CM-DiI-labeled exosomes readily entered keratinocytes and fibroblasts, and that ERCM not only facilitated the proliferation of keratinocytes in normal condition, but also protected against H2O2 cytotoxicity in a concentration-dependent manner. In cell-migration assay, the scratch wound in keratinocyte culture dish was rapidly closed by treatment with ERCM. Such wound-healing effects of ERCM were confirmed in a rat whole skin-excision model: i.e., the wound closure was significantly accelerated by topical application of ERCM solution (4 x 109 exosome particles/100 μL) at 4-day intervals. In the wounded skin, the deposition of collagens was enhanced by treatment with ERCM, which was supported by the increased production of collagen-1 and collagen-3. The results indicate that ERCM from AMSCs containing a large amount of GFs and NFs improve wound healing through tissue regeneration not only by facilitating keratinocyte proliferation for skin repair, but also activating fibroblasts for extracellular matrix production.
ARTICLE | doi:10.20944/preprints202307.1267.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: high-intensity broadband optical radiation; pathogens with multiple drug resistance; pulsed xenon lamp; phototherapy devise; wound healing; dose
Online: 19 July 2023 (09:34:21 CEST)
A new approach to the treatment of wound lesions, which are complicated by the presence of polyresistant microflora and a possible immunodeficiency background has been proposed. It involves treating the wound surface with high-intensity pulsed optical radiation of a continuous spectrum, continuously covering the entire UV range (from 200 to 400 nm), visible and near infrared region of the spectrum. A pulsed xenon lamp is used as a radiation source. A description of the design and technical characteristics of the developed device for high-intensity optical irradiation "Zarnitsa-A", which implements the proposed medical technology for wound therapy, is represented. The results of preclinical studies of the apparatus in vitro and in vivo are represented hereinafter. The article shows that the apparatus exposure has pronounced bactericidal and wound-healing properties. The apparatus action reliably provides higher rates of wound healing compared to the use of only a typical antibacterial and wound healing agent – “Levomekol” ointment.
ARTICLE | doi:10.20944/preprints202307.2057.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Antioxidant; Anti-inflammation, Carboxymethyllysine; High-density lipoproteins; Wound healing, tissue regenration
Online: 31 July 2023 (10:59:46 CEST)
Ozonated sunflower oil (OSO) is an established therapeutic agent and nutraceutical harboring various therapeutic values, including antiallergic, derma-protective, and broad-spectrum antimicrobial activity. Conversely, the medicinal aspects of OSO for wound healing, tissue regeneration, and treatment of inflammation in dyslipidemia have yet to be fully elucidated. Herein, a comparative effect of OSO and sunflower oil (SO) was investigated to heal cutaneous wound and tissue regeneration of zebrafish impediment by carboxymethyllysine (CML) toxicity, following impact on hepatic inflammation and blood lipid profile. After OSO (final 2%, 1 μL) and SO's (final 2%, 1 μL) treatment, substantial healing was elicited by OSO in the cutaneous wound of zebrafish impaired by CML (final 25 mg). As an important event of wound healing, OSO scavenges the reactive oxygen species (ROS), rescues the wound from oxidative injury, and triggers the essential molecular events for the wound closer. Furthermore, the intraperitoneal injection of OSO was noted to counter the CML-induced adversity and prompt tissue regeneration in the amputated tail fin of zebrafish. Additionally, OSO counters the CML-induced neurotoxicity and rescues the zebrafish from acute mortality and paralysis, along with meticulous recovery of hepatic inflammation, fatty liver changes, and diminished ROS and proinflammatory interleukin (IL)-6 production. Besides, OSO efficiently ameliorated CML-induced dyslipidemia by alleviating the total blood cholesterol (TC), triglyceride (TG) and increasing high-density lipoproteins cholesterol (HDL-C). The outcome of multivariate assessment employing principal component analysis and hierarchical cluster analysis supports a superior therapeutic potential of OSO over SO against the clinical manifestation of CML. Conclusively, OSO owing to its antioxidant and anti-inflammatory potential, counters CML-induced toxicity and promotes wound healing, tissue regeneration, hepatoprotection, improved blood lipid profile, and survivability of zebrafish.
ARTICLE | doi:10.20944/preprints202304.0619.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: wound healing; natural compound; excisional mouse model; molecular docking; dynamic molecular; caryophyllene; cytokines; digital histology
Online: 20 April 2023 (07:42:54 CEST)
Dysregulation of the arsenal of cells, growth factors, cytokines, proteases, and proteins involved in wound healing (WH), could delay the healing process. Plants and plant-derived molecules (PDMs) have been used as medicines for skin wounds. This study aimed to select and evaluate the pro-healing capacity of PMDs. Thirty-three PDMs and 10 therapeutic targets (TTs) were chosen for molecular docking and PDMs: aristolochic acid (AA), α-copaene, selinenes, β-caryophyllene (BC), and BCoxide, and TTs: metalloproteinase (MMP) 3, MMP13, and tumor necrosis factor (TNF α) for molecular dynamics. The bests inhibitor was AA, but because of its toxicity, BC and BCoxide were chosen for evaluation in HaCat cells and BALB/c mice excisional model. Both compounds were not toxic, and higher percentages of lesion area closure (LAC) were induced by BC treatment (p<0.05). All mice healed; however, an initial delay of LAC was induced by 0.05, 0.1% BCoxide, 0.1% BC, and allantoin. At the end of treatment, lower numbers of mast cells, level of cellular infiltrates (except 1% BCoxide and 0.05, 0.5%BC), epidermal thickness tendency (except 0.1, 0.5% BCoxide), and higher values of SC-thickness, and collagen fibers only by 0.5% BC treatment compared with untreated control (p<0.05) were observed. Our results show that BC is a promising multitarget candidate for wound healing treatment and optimization campaigns.
REVIEW | doi:10.20944/preprints202012.0578.v2
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Unfolded protein response; Endoplasmic reticulum stress; Glucose-regulated protein 78 kD; Inflammatory Bowel Diseases; Crohn’s disease; Fibrosis; Wound healing
Online: 12 January 2021 (17:03:10 CET)
Endoplasmic reticulum (ER) stress triggers a series of signaling and transcriptional events termed the unfolded protein response (UPR). Severe ER stress is associated with the development of fibrosis in different organs including lung, liver, kidney, heart, and intestine. ER stress is an essential response of epithelial and immune cells in the pathogenesis of inflammatory bowel disease (IBD) including Crohn’s disease. Intestinal epithelial cells are susceptible to ER stress-mediated damage due to secretion of a large amount of proteins that are involved in mucosal defense. In other cells, ER stress is linked to myofibroblast activation, extracellular matrix production, macrophage polarization, and immune cell differentiation. This review focuses on the role of UPR in the pathogenesis in IBD from an immunologic perspective. The roles of macrophage and mesenchymal cells in the UPR from in vitro and in vivo animal models are discussed. The links between ER stress and other signaling pathways such as senescence and autophagy are introduced. Recent advances in the understanding of the epigenetic regulation of UPR signaling are also updated here. The future directions of development of the UPR research and therapeutic strategies to manipulate ER stress levels are also reviewed.
COMMUNICATION | doi:10.20944/preprints202311.1137.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: amniotic membrane stem cell; exosome-rich conditioned medium (ERCM); growth factor; neurotrophic factor; wound healing; keratinocyte proliferation; collagen synthesis; angiogenesis
Online: 17 November 2023 (07:53:56 CET)
Tissue regeneration is an essential requirement for wound healing and recovery of organs’ function. It has been demonstrated that wound healing can be facilitated by activating paracrine signaling mediated by exosomes secreted from stem cells, since exosomes deliver many functional molecules including growth factors (GFs) and neurotrophic factors (NFs) effective for tissue regeneration. In this study, an exosome-rich conditioned medium (ERCM) was collected from human amniotic membrane stem cells (AMSCs) by cultivating the cells under a low oxygen tension (2% O2 and 5% CO2). The contents of GFs and NFs including keratinocyte growth factor, epidermal growth factor, fibroblast growth factor 1, transforming growth factor-β, and vascular endothelial growth factor responsible for skin regeneration were much higher (10-30 folds) in the ERCM than in normal conditioned medium (NCM). In was found that CM-DiI-labeled exosomes readily entered keratinocytes and fibroblasts, and that ERCM not only facilitated the proliferation of keratinocytes in normal condition, but also protected against H2O2 cytotoxicity. In cell-migration assay, the scratch wound in keratinocyte culture dish was rapidly closed by treatment with ERCM. Such wound-healing effects of ERCM were confirmed in a rat whole skin-excision model: i.e., the wound closure was significantly accelerated, remaining minimal crusts, by topical application of ERCM solution (4 x 109 exosome particles/100 μL) at 4-day intervals. In the wounded skin, the deposition of collagens was enhanced by treatment with ERCM, which was supported by the increased production of collagen-1 and collagen-3. In addition, enhanced angiogenesis in ERCM-treated wounds was confirmed by increased von Willebrand factor (vWF)-positive endothelial cells. The results indicate that ERCM from AMSCs with high concentrations of GFs and NFs improves wound healing through tissue regeneration not only by facilitating keratinocyte proliferation for skin repair, but also activating fibroblasts for extracellular matrix production, in addition to the regulation of angiogenesis and scar tissue formation.
ARTICLE | doi:10.20944/preprints202211.0159.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: care wound; wound diabetic; honey; staphylococcus aureus
Online: 9 November 2022 (01:07:32 CET)
Background : Diabetic wounds are very easy to experience complications in the form of infection due to bacterial invasion, and sugar conditions blood which tall encourage the growth of bacteria.Bacteria that can cause infection in diabetic wounds wrong one is staphylococci aureus . Wound diabetes can treated with honey. Honey contains antibacterial , antioxidant and hydrogen peroxide properties that help kill bacteria dangerous. Objective : The purpose of this study was to determine the effect of the wound dressing contains honey against bacterial colonization Staphylococcus aureus on wound diabetic . Methods : The research design used is pre-experimental with o ne-group pre-test and post-test design . Sampling method using consecutive sampling as many as 7 respondents. Results : Analysis data use test dependent t-test and obtained score p value 0.000 ( p value < = 0.05), so could concluded there is influence care wound use honey to colonization bacteria Staphylococcus aureus in wounds diabetic Diabetes Mellitus patients in the region work Public health center Banjarmasin . Conclusion : best Use honey as product care wound because nature the antibacterial which could prevent infection and speed up process healing wound .
REVIEW | doi:10.20944/preprints202109.0511.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: Wound; chronic wound; hypoxia; Lactate; Acidosis; Alkalosis; neoangiogenesis; ECM; Polylactide; polylactide membranes
Online: 30 September 2021 (12:18:52 CEST)
: Over time, we have come to recognize a very complex network of physiological changes enabling wound healing. An immunological process enables the body to distinguish damaged cells and begin a cleaning mechanism by separating damaged proteins and cells with matrix metallopro-teinases, a complement reaction, and free radicals. A wide variety of cell functions help to rebuild new tissue, dependent on energy provision and oxygen supply. Like in an optimized "biorector," disturbance can lead to prolonged healing. One of the earliest investigated local factors is the pH of wounds, studied in close relation to the local perfusion, oxygen tension, and lactate concentration. Granulation tissue with the wrong pH can hinder fibroblast and keratinocyte division and pro-liferation, as well as skin graft takes. Methods for influencing the pH have been tested, such as occlusion and acidification by the topical application of acidic media. In most trials, this has not changed the wound's pH to an acidic one, but it has reduced the strong alkalinity of deeper or chronic wound. Energy provision is essential for all repair processes. New insights into the metabolism of cells have changed the definition of lactate from a waste product to an indispensable energy provider in normoxic and hypoxic conditions. Neovascularization depends on oxygen provision and lactate, signaling hypoxic conditions even under normoxic conditions. An appropriate pH is necessary for successful skin grafting; hypoxia can change the pH of wounds. This review describes the close interconnections between the local lactate levels, metabolism, healing mechanisms, and pH. Furthermore, it analyzes and evaluates the different possible ways to support metabolism, such as lactate enhancement and pH adjustment. The aim of wound treatment must be the optimization of all these components. Therefore, the role of lactate and its influence on wound healing in acute and chronic wounds will be assessed.
ARTICLE | doi:10.20944/preprints202004.0117.v1
Subject: Medicine And Pharmacology, Surgery Keywords: acute compartment syndrome; negative pressure wound therapy; vacuum assisted wound closure; fasciotomy
Online: 8 April 2020 (04:50:32 CEST)
Background and Objectives: Acute compartment syndrome (ACS) is an emergency condition of the lower limb in which prophylactic fasciotomy is required to prevent complications. A negative pressure wound therapy (NPWT) used to the treatment of fasciotomy wounds provide beneficial clinical results. This study aimed to exchange the authors’ experience of using the NPWT installation system on the lower limb wounds after fasciotomy in ACS. Materials and Methods: This is a retrospective study enrolled consecutive patients with ACS, who underwent fasciotomy and was treated with the NPWT installation system at Department of Vascular Surgery, Provincial Hospital in Kielce from April 2016 to July 2017. Results: The study enrolled 15 patients with a diagnosis of ACS (87% men, mean age 65 years old). An open four-compartment fasciotomy (87%) or two-compartment fasciotomy (13%) was performed. The NPWT was applied on the first day after fasciotomy in 87% of patients. Therapy was initiated by the negative pressure of 125 mm Hg, which maintained at this level until the therapy was finalized. In 80% of patients, the vacuum-assisted wound closure (VAC) dressing changes were performed every 3 days. The first approximation of fasciotomy wounds margins occurred on the 4th day after surgery among 67% of individuals. The average time of using VAC on fasciotomy wounds was 9 days. The average time to definitive closure edges of fasciotomy wounds was 12 days. The average time of hospital stay was 17 days. Conclusions: Our experience indicates the legitimacy of using NPWT in wound treatment after fasciotomy in ACS. The NPWT enables faster primary closure of wounds, reduces edema, as well as decreases hospitalization time.
ARTICLE | doi:10.20944/preprints201801.0063.v1
Subject: Medicine And Pharmacology, Veterinary Medicine Keywords: spider venom; wound repair; loxoscelism.
Online: 8 January 2018 (10:49:36 CET)
We studied the efficacy of mesenchymal stem cells (MSC), either alone or associated with dapsone (DAP) in the treatment of dermonecrotic wounds caused by Loxosceles laeta spider venom. Twenty-five male adult rabbits were distributed into five groups, of which four groups received an intradermal injection of 20 μg of L. laeta venom and only one received ultrapure water (negative control). After 4 hours, each group that received venom, was treated with MSC, DAP, MSC + DAP and Phosphate-buffered saline – PBS (positive control). Photographic records were made for analysis of the wound area evolution by morphometry. Twelve days after treatment, the skin samples around the lesion were removed for subsequent histological analysis. Concerning the rate of wound contraction, we observed that DAP showed the best percentage of contraction at day 3. In the treatments using MSCs, a negative value of wound contraction was observed for the isolated MSCs, as well as a lower contraction value for the association of the MSC + DAP when compared to PBS group. Histopathological analysis showed diminished tissue lesion and less intense inflammation in MSCs and DAP groups. This could indicated potential use of stem cells in regenerative therapies after loxoscelic accidents.
ARTICLE | doi:10.20944/preprints202310.1416.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Polyphenolic-gold nanoparticles conjugates; wound healing model; FTIR analyses of wound re-pair tissue
Online: 23 October 2023 (08:35:45 CEST)
Gold nanoparticles (AuNPs) have been used in a broad range of applications conferring to bio-molecules diverse proprieties such as deliver, stabilization and reduction of adverse effects of drugs or plant ex-tracts. Polyphenolic compounds from Bacopa procumbens (BP) are able to modulate proliferation, adhesion, migration and cell differentiation, reducing artificial scratch area in fibroblast cultures and promoting wound healing in in vivo model. Here, chemically synthetized AuNPs conjugated with BP (AuNP-BP) were characterized by Uv-Vis, ATR-FTIR, DLS and zeta-potential. Results showed over-lapping FTIR spectra of polyphenolic compounds from B. procumbens capping the AuNPs, stable size by the DLS and zeta potential, AuNP-BP was 44.58 nm, the zeta-potential of AuNPs was -36.3±12.3 mV after conjugation with the BP; - (AuNP-BP), the zeta-potential was reduced to -18-2±7.02 mV. Enhancement of wound healing effect were evaluated by morphometric, histochemical and FTIR changes in rat wound excision model. Results showed that the nanoconjugation process reduced 100 folds BP concentrations to have the same wound healing effect of BP alone. Besides histological and FTIR spec-troscopy analyses, demonstrated that AuNP-BP treatment displayed better macroscopical performance; the reduction on inflammatory cells, and the increased synthesis and better organization of collagen fibers.
ARTICLE | doi:10.20944/preprints202305.0451.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: Electrospun wound dressing; Skin tissue engineering; Regenerative medicine; Gelatin; Poly (glycerol sebacate); Diabetic wound
Online: 8 May 2023 (05:15:40 CEST)
Infectious diabetic wounds can result in severe injuries or even death. Biocompatible wound dressings offer one of the best ways to treat these wounds, but creating a dressing with suitable hydrophilicity and biodegradation rate can be challenging. To address this issue, we used the electrospinning method to create a wound dressing composed of poly(glycerol sebacate) (PGS) and gelatin (Gel). We dissolved the PGS and Gel in acetic acid (75 v/v%) and added EDC/NHS solution as a crosslinking agent. Our measurements revealed that the scaffolds' fiber diameter ranged from 180.2 to 370.6 nm, and all the scaffolds had porosity percentages above 70%, making them suitable for wound healing applications. Additionally, we observed a significant decrease (p < 0.05) in the contact angle from 110.8° ± 4.3° for PGS to 54.9° ± 2.1° for PGS/Gel scaffolds, indicating an improvement in hydrophilicity of the blend scaffold. Furthermore, our cell viability evaluations demonstrated a significant increase (p < 0.05) in cultured cell growth and proliferation on the scaffolds during the culture time. Our findings suggest that the PGS/Gel scaffold has potential for wound healing applications.
ARTICLE | doi:10.20944/preprints202311.1874.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: Wound; Scar; Child; Graft; Fish skin
Online: 29 November 2023 (10:58:49 CET)
Wound healing in the pediatric population is known to be a challenge and poorly studied. Split-thickness skin grafts, full-thickness skin grafts and flaps overlap their applications with the growing field of cellular and tissue-based therapies. However, their role in pediatric reconstruction has yet to be defined. The Kerecis® Omega3 wound patch, derived from decellularized codfish skin, has garnered attention due to its preserved microscopic architecture resembling the human extracellular matrix. This acellular dermal matrix acts as a scaffold, fostering dermal cell and capillary adhesion while harnessing omega-3 polyunsaturated fatty acids for granulation acceleration and antimicrobial effects. This study presents a comprehensive review and surgical protocol for utilizing Kerecis® fish skin in pediatric wound care. The research embraces a case series involving five patients with diverse wound locations. The Kerecis® Omega3 wound patch underwent meticulous application and careful monitoring. The results highlight an average time of 48.6 days for complete epithelialization, yielding favorable outcomes with no hypertrophic scarring and mild retraction. Notably, this innovative approach may eliminate donor site morbidity and improve pain control, promising a novel avenue for pediatric wound management.
ARTICLE | doi:10.20944/preprints202303.0431.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Cancer; wound healing; exaptation; somatic evolution
Online: 24 March 2023 (12:35:04 CET)
Cancers have been interpreted either as somatic evolution of cheater cells that escape replication regulation or alternatively as non-healing wounds. Both the interpretations have substantial support as well as glaring anomalies but the two have not been put together to make a coherent synthesis. We argue here that mechanisms and pathways to escape the normal regulation of cell proliferation do not need to evolve de novo. Mechanisms to override the normal regulation have already evolved for wound healing and tissue regeneration. Almost all of the hallmarks of cancer are also seen in the wound healing process. This suggests that cancer develops not by any de novo gain of function but by exaptation of pre-evolved wound healing functions. Somatic evolution that makes the wound healing triggers constitutive is not mutation limited but selection limited and the selective forces are dependent on the tissue microenvironment. Some mechanisms for such selection have been suggested. Many more need to be investigated. A series of mechanisms have evolved to minimize the risk of cancers which may fail in an altered lifestyle context. We support our synthesis with multiple lines of evidence and also make differential testable predictions. This evolutionary perspective suggests novel lines of research and also has translatable implications for cancer prevention.
REVIEW | doi:10.20944/preprints202212.0048.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: poly(hexamethylene biguanide); polyhexamethylene biguanide; polyhexanide; PHMB; membrane; controlled drug release; wound dressing; antimicrobial; cytotoxicity; wound healing
Online: 2 December 2022 (10:31:38 CET)
The prevalence for chronic, non-healing skin wounds in the general population, most notably diabetic foot ulcers, venous leg ulcers and pressure ulcers, is approximately 2% and is expected to increase, driven mostly by an aging population and the steady rise in obesity and diabetes. Non-healing wounds often become infected, increasing the risk of life-threatening complications, which poses a significant socioeconomic burden. Aiming at an improved management of infected wounds, a variety of wound dressings incorporating antimicrobials (AMDs), namely polyhexanide (poly(hexamethylene biguanide); PHMB), have been introduced in the wound care market. However, many wound care professionals agree that none shows comprehensive and optimal antimicrobial activity. This manuscript summarizes and discusses studies on novel PHMB-releasing membranes (PRMs) for wound dressings, detailing their preparation, physical properties relevant in the context of AMDs, drug loading and release, antibacterial activity, biocompatibility, wound healing capacity, and clinical trials conducted. Some of these PRMs were able to improve wound healing in in vivo models, with no associated cytotoxicity, but significant differences in study design make it difficult to compare overall effi-cacies. It is hoped that this review, which includes, whenever available, international standards for testing AMDs, will provide a framework for future studies.their preparation, physical properties relevant in the context of AMDs, drug loading and release, antibacterial activity, biocompatibility, wound healing capacity, and clinical trials conducted. Some of these PRMs were able to improve wound healing in in vivo models, with no associated cytotoxicity, but significant differences in study design make it difficult to compare overall efficacies. It is hoped that this review, which includes, whenever available, international standards for testing AMDs, will provide a framework for future studies.
ARTICLE | doi:10.20944/preprints202310.1432.v1
Subject: Biology And Life Sciences, Aging Keywords: Lipogenesis; depigmenting activity; aging; senescence; wound healing
Online: 23 October 2023 (15:25:57 CEST)
As global life expectancy continues to rise, we are challenged with maintaining health into old age, and research has thus concentrated on various strategies aimed at mitigating the effects of skin aging. Aromatic plants stand out as potential sources of anti-aging compounds due to their secondary metabolites, particularly essential oils (EO). The aim of this study was to ascribe to Ferulago lutea EO several biological activities that could be useful in the context of skin aging. The EO was obtained using hydrodistillation and characterized by gas chromatography-mass spectrometry (GC/MS). The anti-inflammatory potential was assessed using lipopolysaccharide (LPS)-stimulated macrophages. The effect on cell migration was disclosed using scratch wound assay. Lipogenesis was induced using T0901317, hyperpigmentation with 3-isobutyl-1-methylxantine (IBMX) and senescence with Etoposide. Our results show that the EO was characterized mainly by α-pinene and limonene. The EO was able to decrease nitric oxide (NO) release as well as iNOS and pro-IL-1β protein levels. The EO promoted wound healing while decreasing lipogenesis and having depigmenting effects. The EO also reduced senescence associated β-galactosidase and p21/p53 protein levels and nuclear accumulation of γH2AX. Overall, our study highlights the properties of F. lutea EO that make it a compelling candidate for dermocosmetics applications.
ARTICLE | doi:10.20944/preprints202309.1045.v1
Subject: Medicine And Pharmacology, Surgery Keywords: surgical wound; dimensional measurement accuracy; surgical flap
Online: 15 September 2023 (05:18:23 CEST)
The accurate assessment of wound size is a critical step in advanced wound care management. This study aims to introduce and validate a Light Detection and Ranging (LiDAR) technique for measuring wound size. Twenty-eight wounds treated from December 2022 to April 2023 at the Chunganam National University Hospital were analyzed. All wounds were measured using three techniques; conventional ruler methods, the LiDAR technique, and ImageJ analysis. Correlation analysis, linear regression, and Bland-Altman plot analysis were conducted to validate the accuracy of the newly introduced method. The measurement results (Mean ± Standard deviation) obtained using the Ruler method, LiDAR technique, and ImageJ analysis were 112.99 ± 110.07 cm², 73.59 ± 72.97 cm², and 74.29 ± 72.15 cm², respectively. The Pearson correlation coefficient was higher in the LiDAR application (0.995) than the conventional ruler methods (Mean difference; -5.0000 cm2), as was the degree of agreement (Mean difference; 38.6933 cm2). Wound size measurement using LiDAR is a simple and reliable method that allows practitioners to conveniently assess wounds with a flattened and irregular shape. However, non-flattened wounds cannot be assessed owing to the technical limitations of LiDAR.
ARTICLE | doi:10.20944/preprints202305.0293.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: P-ELISA; exosome; microRNA-21; wound healing
Online: 5 May 2023 (04:07:53 CEST)
Emerging evidence has shown that microRNAs play pivotal roles in wound healing. MicroRNA-21 (miR-21) was previously found to upregulate in order to fulfill an anti-inflammation role for wounds. Exosomal miRNAs have been identified and explored as essential markers for diagnostic medicine. However, the role of exosomal miR-21 in wounds has yet to be well studied. In order to facilitate the early management of poorly healing wounds, we developed an easy-to-use, rapid, paper-based microfluidic-exosomal miR-21 extraction device to determine wound prognosis in a timely manner. We isolated and then quantitatively examined exosomal miR-21 in wound fluids from normal tissues, acute and chronic wounds. Eight improving wounds displayed lower levels of exosomal miR-21 expression after wound debridement. However, four instances of increased exosomal miR-21 expression levels were notably associated with patients with poor healing wounds despite aggressive wound debridement, indicating a predictive role of tissue exosomal miR-21 for wound outcome. Paper-based nucleic acid extraction device provides a rapid and user-friendly approach for evaluating exosomal miR-21 in wound fluids as a means of monitoring wounds. Our data suggest that tissue exosomal miR-21 is a reliable marker for determining current wound status.
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: wound infections; snakebites; Taiwan cobra; Naja atra
Online: 27 January 2021 (13:06:10 CET)
Taiwan cobra (Naja atra) bites account for approximately 20% of all venomous snakebites in Taiwan. In Taiwan, the rates of wound necrosis and secondary infection from Taiwan cobra bites are higher than those associated with other venomous snakebites. Clinical tools to evaluate the infection risk after Taiwan cobra bites are lacking. Therefore, in this study, we developed a useful clinical tool to evaluate the infection risk after Taiwan cobra bites. Moreover, we investigated wound infection bacteriology. We analyzed the data of patients bitten by N. atra who had undergone freeze-dried neurotoxic antivenin treatment in emergency rooms of the Chang Gung Memorial Hospital network, which comprises seven hospitals and the largest medical system in Taiwan, from January 2001 to May 2017. Because patients with wound necrosis required antibiotics for infection treatment, we included only patients with wound infection but without tissue necrosis in the development of our Cobra Bacteriology of Infections in Taiwanese snake Envenomation (Cobra BITE) score by using univariate and multiple logistic regression. In total, 8,295,497 emergency department visits occurred from January 2001 to May 2017, and 195 patients were diagnosed has having cobra bites. Among them, 23 and 30 patients had wound necrosis and wound infection, respectively. The wound infection rate was 27.2% (53/195). Regardless of whether the patients had necrosis, Enterococcus faecalis and Morganella morganii were the main bacteria identified in the culture report. Gentamicin, ceftriaxone, ciprofloxacin, and levofloxacin are the ideal first-line antibiotics for treating N. atra bite wounds in Taiwan. As per our Cobra BITE score, the three factors predicting secondary wound infection after cobra bites are hospital admission, a white blood cell count (in 103/µL) × by neutrophil–lymphocyte ratio value of ≥114.23, and the use of antivenin medication. The area under the receiver operating characteristic curve for the Cobra BITE score system was 0.88. The ideal sensitivity and specificity were 0.89 and 0.76, respectively, and the optimal cutoff point for Cobra BITE score was 7. The Hosmer–Lemeshow p value was 0.4. In conclusion, our Cobra BITE study established a new practical clinical tool for clinicians to evaluate infection risk after N. atra bites. This score system enables the assessment of wound infections after N. atra bites, and it could be modified and improved in future for other Naja spp. bites.
ARTICLE | doi:10.20944/preprints201905.0235.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: chronic wound; hospital cost; epidemiology; public health
Online: 20 May 2019 (09:53:44 CEST)
Background: Chronic lower limb ulcers (CLLU) have an important burden to the individual and the healthcare system. However, there is a lack of information about the cost of CLLU in Argentina.Objective: To determinate the number and cost of consultation and hospitalization associated to CLLU in a public hospital in Argentina. Methods: Retrospective observational study. Cost estimation were calculated based on days of stay, treatments and laboratory tests in a inpatient population and the number of consultations, treatments and laboratory tests, in a outpatient population. Results: In 2013 and 2014, the overall number of consultation with ICD-10 codes was 7,224 and the number of inpatient was 359. The mean age for male and female outpatient consultations was 59.53(±13.06) years and 59.04(±10.93), respectively. For CLLU male and female inpatient, the mean age was 63.9(±10.4) years and 54.5(±8.6) years, respectively. The length of stay was 22.88 days. There was a mean of 0.41 surgeries per patient where 25% were amputations. The mean annual cost in a single public hospital was US$4,053.65 per inpatient and US$3,589.24 per outpatient. Conclusion: Cost information allows new public health policies to reduce socioeconomic burden due to CLLU.
REVIEW | doi:10.20944/preprints202305.1106.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: photothermal-antimicrobials; antibacterial mechanisms; anti-biofilm; wound healing
Online: 16 May 2023 (05:40:58 CEST)
Rapid developing antimicrobial resistance due to broad antibiotic utilisation in healthcare and food industries and the non-availability of novel antibiotics represents one of the most critical public health issues worldwide. The current advances in nanotechnology allow new materials to address drug-resistant bacterial infections in specific, focused and biologically safe ways. The unique physicochemical properties, biocompatibility, and wide range of adaptability of nanomaterials that exhibit photothermal capability can be employed to develop the next generation of photothermally induced controllable hyperthermia as antibacterial nanoplatforms. Here, we review the current state-of-the-art in different functional classes of photothermal antibacterial nanomaterials and the strategies to optimise antimicrobial efficiency. The recent achievements and trends in developing photothermally active nanostructures, including plasmonic metals, semiconductor, carbon-based, and organic photothermal polymers, and antibacterial mechanisms of action, including anti-multidrug resistant bacteria and biofilms removal, will be discussed. Insights into mechanisms of the photothermal effect and various factors influencing photothermal antimicrobial performance, emphasising the structure–performance relationship, are discussed. We will examine the photothermal agents’ functionalisation for specific bacteria, effects of near-infrared light irradiation spectrum, or active photothermal materials for multimodal synergistic-based therapies to minimise side effects and maintain low cost. Most relevant applications are presented, such as anti-biofilm formation, biofilm penetration or ablation, and nanomaterial-based infected wound therapy. Practical antibacterial applications employing the photothermal antimicrobial agents, alone or in synergistic combination with other nanomaterials, are considered. Existing challenges and limitations in photothermal antimicrobial therapy and future perspectives are presented from the structure, function, safety, and clinical potential points of view.
REVIEW | doi:10.20944/preprints202207.0040.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Kalanchoe; antibacterial; anti-inflammatory properties; wound healing; antioxidant
Online: 4 July 2022 (08:27:24 CEST)
The Kalanchoe genus is composed of more than 100 species that usually thrive in tropical environments, which have been used in folkloric medicine to treat various illnesses, including dermatological conditions. With this, the present study assesses the pharmacognostical and pharmacological properties of different species of the Kalanchoe genus as elements for a potential treatment for dermatological-related conditions, from findings of existing literature and studies. It was analyzed that the Kalanchoe pinnata plant, or one of the most common species of Kalanchoe, have been observed to have distinct morphological and microscopic characteristics. Further, it was discovered that different species of Kalanchoe have anti-inflammatory, antioxidant, antibacterial, and wound healing properties, which enable the plant to be used for dermatological products that are available to the market. With this, it is recommended that further studies be conducted in other understudied species of Kalanchoe regarding their pharmacological properties, as well as the use of other structures of the Kalanchoe plant for treatment of various dermatological conditions.
Subject: Biology And Life Sciences, Plant Sciences Keywords: Regeneration; asexual propagation; multicellular organisms; wound repair; maturation
Online: 19 August 2021 (11:27:26 CEST)
Regeneration is usually regarded as a unique plant or some animal species process. In reality, regeneration is a ubiquitous process in all multicellular organisms. It ranges from response to wounding by healing the wounded tissue to whole body neoforming (remaking of the new body). In a larger context, regeneration is one facet of two reproduction schemes that dominate the evolution of life. Multicellular organisms can propagate their genes asexually or sexually. Here I present the view that the ability to regenerate tissue or whole-body regeneration is also determined by the sexual state of the multicellular organisms (from simple animals like hydra and planaria to plants and complex animals). The above idea is manifested here by showing evidence that many organisms, organs, or tissues show inhibited or diminished regeneration capacity when in reproductive status compared to the same organism organs or tissues in nonreproductive conditions or by exposure to sex hormones.
ARTICLE | doi:10.20944/preprints202101.0346.v1
Subject: Engineering, Control And Systems Engineering Keywords: Chronic wound classification; transfer learning; explainable artificial intelligence.
Online: 18 January 2021 (14:28:04 CET)
Artificial Intelligence (AI) has seen increased application and widespread adoption over the past decade despite, at times, offering a limited understanding of its inner working. AI algorithms are, in large part, built on weights, and these weights are calculated as a result of large matrix multiplications. Computationally intensive processes are typically harder to interpret. Explainable Artificial Intelligence (XAI) aims to solve this black box approach through the use of various techniques and tools. In this study, XAI techniques are applied to chronic wound classification. The proposed model classifies chronic wounds through the use of transfer learning and fully connected layers. Classified chronic wound images serve as input to the XAI model for an explanation. Interpretable results can help shed new perspectives to clinicians during the diagnostic phase. The proposed method successfully provides chronic wound classification and its associated explanation. This hybrid approach is shown to aid with the interpretation and understanding of AI decision-making processes.
ARTICLE | doi:10.20944/preprints202002.0430.v2
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Co-culture; Reduced-serum; Wound bed; Fibroblasts; Keratinocytes
Online: 12 March 2020 (13:24:46 CET)
Contact-based co-culture of fibroblasts and keratinocytes is important to study the structure and functions of the wound bed. Co-culture of these two cell types in direct contact with each other has been challenging, requiring high serum concentrations (up to 10%), feeder systems and a range of supplemental factors. These approaches are not only technically demanding, but also present scientific, cost and ethical limitations associated with high-serum concentrations. We have developed two reduced-serum approaches (1-2%) to support contact-based co-culture of human dermal fibroblasts (HDFa) and human epidermal keratinocytes (HaCaT). The two approaches include (1) Specialized cell culture media for each cell type mixed in a 1:1 ratio (KGM+FGM), and (2) Minimal media supplemented with cell-specific growth factors (MEM+GF). Co-culture could be successfully achieved by co-seeding (two cell types were introduced simultaneously), or in a layered fashion (keratinocytes seeded on top of confluent fibroblasts). With wound scratch assays, the co-cultured platforms could demonstrate cell proliferation, migration and wound closure. The reduced-serum conditions developed are simple, easy to formulate and adopt, and based on commonly-available media components. These contact-based co-culture approaches can be leveraged for wound and skin studies, and tissue bioengineering applications, potentially reducing concerns with high-serum formulations.
REVIEW | doi:10.20944/preprints201906.0094.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Bacteriophages, Septic wound infection, MDR, Biofilms, Phage Cocktails
Online: 11 June 2019 (10:08:07 CEST)
Lytic bacteriophages have the efficacy to act and eradicate pathogenic bacteria as an attractive tool in the near future. Bacteriophages specifically kill multidrug-resistant bacteria even which have the capacity to form biofilms. The present review mainly focused on the efficacy of bacteriophages and cocktails as therapeutic agents against predominate MDR-bacteria and their biofilms which are isolated from septic wound infections. The body of evidence includes data from studies investigating bacteriophages from sewage samples as novel antibacterial and antibiofilm agents against pathogenic bacteria. The goal of this review is to present an overview on predominant bacteria from septic wound infection, the biofilm-forming capacity of bacteria, lytic effect of bacteriophages and phage cocktails with an emphasis on the application of bacteriophages against septic wound causing bacteria.
REVIEW | doi:10.20944/preprints201805.0396.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: diabetes; chronic wounds; smart wound dressing; biochemical sensor
Online: 28 May 2018 (10:22:39 CEST)
Given their severity and non-healing nature, diabetic chronic wounds are a significant concern to the 30.3 million Americans diagnosed with diabetes mellitus (2015). Peripheral arterial diseases, neuropathy, and infection contribute to the development of these wounds, which lead to an increased incidence of lower extremity amputations. Early recognition, debridement, offloading, and controlling infection are imperative for timely treatment. However, wound characterization and treatment are highly subjective and based largely on the experience of the treating clinician. Many wound dressings have been designed to address particular clinical presentations, but a prescriptive method is lacking for identifying the particular state of chronic, non-healing wounds. The authors suggest that recent developments in wound dressings and biosensing may allow for the quantitative, real-time representation of the wound environment, including exudate levels, pathogen concentrations, and tissue regeneration. Development of such sensing capability could enable more strategic, personalized care at the onset of ulceration and limit the infection leading to amputation. This review presents an overview of the pathophysiology of diabetic chronic wounds, a brief summary of biomaterial wound dressing treatment options, and biosensor development for biomarker sensing in the wound environment.
REVIEW | doi:10.20944/preprints201805.0319.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: annexins; inflammation; wound healing; drug target; translational research
Online: 23 May 2018 (08:19:42 CEST)
The vertebrate annexin superfamily (AnxA) consists of 12 calcium (Ca2+) and phospholipid binding proteins which share a high structural homology. In keeping with this hallmark feature, annexins have been implicated in the Ca2+-controlled regulation of membrane events. In this review, we discuss several themes of potential therapeutic value, namely the regulation of the immune response and the control of tissue homeostasis, that repeatedly surface in the annexin action profile. Our aim is to identify and discuss those annexin properties which might be exploited from a translational science and specifically clinical point of view.
REVIEW | doi:10.20944/preprints202309.0901.v1
Subject: Chemistry And Materials Science, Materials Science And Technology Keywords: hydrogel; natural polymer; drug delivery; tissue engineering; wound healing
Online: 14 September 2023 (04:39:02 CEST)
Hydrogels prepared from natural polymer have attracted extensive attentions in biomedical fields such as drug delivery, wound healing, and regenerative medicine due to their good biocompatibility, degradability and flexibility. This review outlines the commonly used natural polymer in hydrogel preparation, including cellulose, chitosan, collagen/gelatin, alginate, hyaluronic acid and starch. The polymeric structure and process/synthesis of natural polymers are illustrated, and natural polymer-based hydrogels including the hydrogel formation and properties are elaborated. Subsequently, the biomedical application of hydrogels based on natural polymer in drug delivery, tissue regeneration, wound healing and other biomedical field is summarized. Finally, the future perspectives of natural polymers and hydrogels based on them are discussed. For natural polymer, novel technologies such as enzymatic and biological methods are developed to improve the structural properties and the development of new natural based polymers or natural polymer derivatives with high performance is still very important and challenging. For natural polymer-based hydrogels, novel hydrogel materials, like double-network hydrogel, multifunctional composite hydrogels and hydrogel microrobots are designed to meet the advanced requirements in biomedical application, and new strategies such as dual-crosslinking, microfluidic chip, micropatterning and 3D/4D bioprinting, have been explored to fabricate advanced hydrogel materials with designed properties for biomedical application. Overall, natural polymeric hydrogels have attracted increasing interests in biomedical application, and the development of novel natural polymer-based materials and new strategies/methods for hydrogel fabrication is badly desirable and still challenging.
REVIEW | doi:10.20944/preprints202201.0035.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: Cellulose; Biomedical; Wound healing; Drug delivery; Antibacterials; Tissue engineering
Online: 5 January 2022 (11:00:57 CET)
There are various biomaterials in nature, but none fulfills all the requirements. Cellulose, eco-friendly material-based biopolymers, have been advanced biomedicine to satisfy most market demand and circumvent many ecological concerns. This review aims to present an overview of the state of the art in cellulose's knowledge and technical biomedical applications. It included an extensive bibliography of recent research findings for fundamental and applied investigations. The chemical structure of cellulose allows modifications and simple conjugation with several materials, including nanoparticles, without tedious efforts. Cellulose-based materials were used for biomedicine applications such as antibacterial agents, antifouling, wound healing, drug delivery, tissue engineering, and bone regeneration. They advanced the applications to be cheap, biocompatible, biodegradable, easy for shaping and processing into different forms, with suitable chemical, mechanical and physical properties.
ARTICLE | doi:10.20944/preprints202107.0597.v1
Subject: Public Health And Healthcare, Physical Therapy, Sports Therapy And Rehabilitation Keywords: 3D printing; microfabrication; microfluidic guillotine; single cell; wound healing
Online: 27 July 2021 (09:21:04 CEST)
Micro-blade design is an important factor in the cutting of single cells and other biological structures. This paper describes the fabrication process of three dimensional (3D) micro-blades for the cutting of single cells in a microfluidic “guillotine” intended for fundamental wound repair and regeneration studies. Our microfluidic guillotine consists of a fixed 3D micro-blade centered in a microchannel to bisect cells flowing through. We show that the Nanoscribe two-photon polymerization direct laser writing system is capable of fabricating complex 3D micro-blade geometries. However, structures made of the Nanoscribe IP-S resin have low adhesion to silicon, and they tend to peel off from the substrate after at most two times of replica molding in poly(dimethylsiloxane) (PDMS). Our work demonstrates that the use of a secondary mold replicates Nanoscribe printed features faithfully for at least 10 iterations. Finally, we show that complex micro-blade features can generate different degrees of cell wounding and cell survival rates compared with simple blades possessing a vertical cutting edge fabricated with conventional 2.5D photolithography. Our work lays the foundation for future applications in single cell analyses, wound repair and regeneration studies, as well as investigations of the physics of cutting and the interaction between the micro-blade and biological structures.
ARTICLE | doi:10.20944/preprints201806.0130.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: wound healing; catechol; conjugated; antioxidant; antiinflammatory; bioadhesion; UV shielding
Online: 8 June 2018 (12:28:07 CEST)
The effective treatment for chronic wounds constitute one of the most common worldwide health care problem due to the presence of high levels of proteases, free radicals and exudates in the wound, which constantly activate the inflammatory system avoiding the tissue regeneration. In this study, we describe a multifunctional bioactive and resorbable membrane with in-built antioxidant agent for the continuous quenching of free radicals as well as to control inflammatory response helping to promote the wound healing process. To reach that goal synthesized statistical copolymers of N-vinylcaprolactam (V) and 2-hydroxyethyl methacrylate (H) have been conjugated with catechol bearing hydrocaffeic acid (HCA) molecules. The natural polyphenol (catechol) is the key molecule responsible for the mechanism of adhesion of mussels, and provides the functionalized polymer conjugate a continuous antioxidant response, antiinflammatory effect, UV screen and bioadhesion in the moist environment of the human body, all of them key features in the wound healing process. Therefore, these novel mussel-inspired materials have an enormous potential of application and can act very positively, favoring and promoting the healing effect in chronic wounds.
ARTICLE | doi:10.20944/preprints202212.0004.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SMI (silicone mammary implants); FBR (foreign body response); wound healing; wound infection; capsular fibrosis; implant encapsulation; early-stage fibrosis; surface adsorption; immunomics; biomarkers
Online: 1 December 2022 (02:02:11 CET)
The etiology of exaggerated fibrous capsule formation around silicone mammary implants (SMI) is multifactorial but primarily induced by immune mechanisms toward the foreign material silicone. The aim of this work was to enlighten the disease progression from implant insertion and immediate tissue damage response reflected in (a) the acute wound proteome, and (b) the adsorption of chronic inflammatory wound proteins at implant surfaces. An intra-individual absolute quantitation TMT-liquid chromatography-tandem mass spectrometry approach was applied to profile wound proteome formed around SMI the first five days post-implantation. Compared to plasma, the acute wound profile resembled a more complex composition comprising plasma-derived and locally differentially expressed proteins (DEPs). DEPs were subjected to functional enrichment analysis, which revealed the dysregulation of signaling pathways mainly involved in immediate inflammation response and ECM turnover. Moreover, we found time-course variations in protein enrichment immediately post-implantation and adsorbed to SMI surfaces after 6-8 months. Characterization of the expander-adhesive proteome by label-free approach uncovered a long-term adsorbed acute wound and the fibrosis-associated proteome. Our findings propose a wound biomarker panel for the early detection and diagnosis of excessive fibrosis that could potentially broaden insights into the characteristics of fibrotic implant encapsulation.
REVIEW | doi:10.20944/preprints202306.1065.v1
Subject: Medicine And Pharmacology, Surgery Keywords: oxidative stress; dressing; lactate; polylactide; reactive oxygen species; wound healing
Online: 14 June 2023 (15:32:50 CEST)
Although a slight imbalance between oxidative and antioxidative mediators is part of normal physiology that enables cell aging and the removal of dead cells, burns disturb this equilibrium locally and systemically. Topical burn dressings may attenuate local and systemic oxidative stress and positively influence the post-burn clinical course. This review integrated knowledge regarding the impact of burn dressings on oxidative stress. Using keywords and in-text searches, literature was identified from PubMed, Google Scholar, and Google articles, and studies on local or topical applications of wound dressings and associated oxidative stress were selected. As im-balances between oxidative mediators and antioxidative agents significantly contribute to organ dysfunction and healing disturbance, we investigated oxidative stress on organs, metabolic changes, clinical results, and oxidative parameters influenced by applied dressings. We found positive local and systemic effects of external burn dressings in laboratory and animal tests; however, such studies were rare in humans. Nevertheless, we identified successful cases of semi-occlusive, occlusive, and biologically active dressings that reduce oxidative stress in hu-man burns. In particular, we highlight promising clinical and laboratory results from lac-tate-releasing dressings. Our review provides an invaluable resource for future development and clinical applications of burn dressings.
ARTICLE | doi:10.20944/preprints202305.0859.v1
Subject: Biology And Life Sciences, Horticulture Keywords: chitosan; foliar application; lignin; potato; suberin polyphenolics; wound-induced suberization
Online: 11 May 2023 (13:35:44 CEST)
Potato tubers are susceptible to wounding during post-harvest processes, leading to quality decline, perishability and large economic losses. In this study, the potato cultivar, ‘Longshu No.7’, was foliar-sprayed with 3% chitosan (w/v) three times during the pre-harvest period after flowering to evaluate the effect of foliar spraying with chitosan on suberization processing at wounds of harvested potato tubers. Our results demonstrate that foliar-sprayed with chitosan significantly reduced wound-induced fresh weight loss and dry rot disease index by 37.34% and 41.60% on the 28 day after wounding, respectively. Foliar-sprayed with chitosan accelerated the deposition of suberin polyphenolics and lignin at the wound sites of potato tubers with the formation of thicker cell layers. This occurred with increased localized activities of key enzymes in the suberin polyphenolics and lignin pathways, including phenylalanine ammonia lyase, 4-coumaryl-coenzyme A ligase, cinnamyl alcohol dehydrogenase and peroxidase (33.90–64.32%), as well as the contents of cinnamic acid, sinapic acid, flavonoids, lignins and total phenolics (19.70–23.46%) at wound sites of potato tubers on the 7 day after wounding. Our results indicated that foliar application of chitosan accelerated wound-induced suberization of potato tubers and could mitigate post-harvest product damages.
ARTICLE | doi:10.20944/preprints202111.0134.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: HPV16; E7 variants; cervical cancer; transformation; wound healing; western blotting
Online: 8 November 2021 (12:28:30 CET)
The human papillomavirus (HPV) type 16 E7 oncogene is critical to carcinogenesis and highly conserved. Previous studies identified a preponderance of non-synonymous E7 variants amongst HPV16-positive cancer-free controls compared to those with cervical cancer. To investigate the function of E7 variants, we constructed full-length HPV16 E7 genes and tested variants at positions H9R, D21N, N29S, E33K, T56I, D62N, S63F, S63P, T64M, E80K, D81N, P92L, and P92S (found only in controls); D14E, N29H (CIN2), and P6L, H51N, R77S (CIN3). We determined the steady-state level of cytoplasmic and nuclear HPV16 E7 protein. All variants from the controls showed a reduced level of steady-state E7 protein, with 7/13 variants having deficient protein levels. In contrast, 2/3 variants from the CIN3 precancer group had near-normal E7 levels. We assayed the activity of representative variants in stably transfected NIH3T3 cells. The H9R, E33K, P92L, and P92S variants found in control subjects had lower transforming activity than D14E and N29H variants (CIN2); and the R77S (CIN3) had activity only slightly reduced from wildtype E7. In addition, R77S and WT E7 caused increased migration of NIH3T3 cells in a wound-healing assay as compared with H9R, E33K, P92L, and P92S (controls) and D14E (CIN2). These data provide evidence that the E7 variants found in HPV16-positive cancer-free women are partially defective for transformation and cell migration further demonstrating the importance of fully active E7 in clinical cancer development.
ARTICLE | doi:10.20944/preprints202105.0207.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Suture material; Third molar surgery; Surgical wound infection; Bacterial adhesion
Online: 10 May 2021 (15:08:53 CEST)
Background: Selection and application of suture materials, has gained more importance especially with the increasing number of patients seeking oral surgeries. Since lying in a bacterial-filled environment, sutures make the tissue prone to infection. Suture material plays an important role in the reduction of the risk of infection. This study aimed to assess the success rate of an antibacterial suture named Vicryl Plus in preventing bacterial growth in the surgical site of the mandibular third molar. Methods: 27 patients were included in this double-blinded randomized clinical trial study. Surgical Extraction of the mandibular wisdom tooth was done and the incision was managed by randomly using Vicryl Plus and Vicryl sutures. After 7 days, sutures were removed and assessed microbiologically. Predominant species of Streptococcus mutans and Lactobacillus were assessed as well as the total number of colonies on each suture. Results: There was a significant difference between two suture materials in colony number-length ratio of lactobacillus (p-value= 0.031) and total bacterial colonies (p-value=0.016); but not for S. mutans species (p-value=0.201). Conclusion: Antibacterial Vicryl suture can be a useful tool for the reduction in the rate of surgical site infection in high-risk cases and situations.
REVIEW | doi:10.20944/preprints202007.0519.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Burn wounds; ZnO NPs; Plant-based Green Synthesis; Wound healing
Online: 22 July 2020 (11:10:15 CEST)
In this changing world, we all are surrounded by the surmountable risk of getting injured. Amongst various risk factors, major burns are the most distressing and catastrophic. Burn wounds are not easy to heal via natural healing process and ultimately ended up with scar formation. If the degree of burn is high then the loss of tissue and its function is very common. To fasten-up the natural burn wound healing; zinc, an essential trace element is found to be very much effective. But due to its’ particle size limitation, less contact with wounded cells and tissues, and high inherent toxicity restrict its use. Needlessly, zinc is an element with dual action i.e. both antimicrobial and wound healing it is a prime choice to apply its aptitude in burn wound healing. To overcome the documented limitations zinc has converted to nanoparticle form. Zinc oxide nanoparticles, in particular, have attained ample of interest due to their unique properties and potential antimicrobial activity along with wound healing activity which makes it promising for the healing of topical burn wounds. Plant mediated green synthesis of nano-metal oxide particles is gaining a lot of significance due to its simplicity, eco-friendliness and extensive antimicrobial activity and recommended as an appealing substitute to not only physical methods but also chemical methods avoiding the use of the high rate of toxic chemicals and extreme surroundings. This study includes ZnO NPs role in burn wound healing with Phyto-mediated synthesis methods to provide evidence of their potential applications. Additionally, it provides an overview of traditional methods used for the synthesis of ZnO nanoparticles and characterization techniques to obtain information concerning the size, shape and optical properties along with toxicity and safety concern of ZnO NPs and its biomedical applications.
REVIEW | doi:10.20944/preprints202007.0284.v1
Subject: Engineering, Bioengineering Keywords: seaweed; sulfated polysaccharides; alginates; fucoidans; carrageenans; ulvans; wound dressing; wounds
Online: 14 July 2020 (03:37:56 CEST)
Wound healing involves a complex cascade of cellular, molecular, and biochemical responses and signaling processes. It consists of successive interrelated phases, the duration of which depends on multifactorial processes. Wound treatment is a major healthcare issue that can be resolved by development of effective and affordable wound dressings based on natural materials and biologically active substances. Proper use of modern wound dressings can significantly accelerate wound healing with minimal cosmetic defects. The innovative biotechnologies for creating modern natural interactive dressings are based on sulfated polysaccharides from seaweeds with their unique structures and biological properties, the availability of their sources in the form of wild bushes, and in the form of aquaculture, as well as with a high potential for participation in process control wound healing. These natural biopolymers are a novel and promising biologically active source for designing wound dressings based on alginates, fucoidans, carrageenans, and ulvans, which serve as active and effective therapeutic tools. The aim of this review is to summarize available information about the modern wound dressing’s technologies based on seaweed-derived polysaccharides, including those successfully implemented in commercial products, with the emphasis on promising and innovative designs. The further prospect of using marine biopolymers is related to the need to analyze the results of numerous in vitro and in vivo experiments, summarize clinical trial data, develop a scientifically based approach and relevant practical recommendations for the treatment of wounds.
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: honey; antimicrobials; methylglyoxal; hydrogen peroxide; bee-defensin 1; wound treatment
Online: 29 October 2019 (10:45:51 CET)
Honey is a complex sweet food stuff with well-established antimicrobial and antioxidant properties. It has been used for millennia in a variety of applications, but those most noteworthy include treatment of surface wounds, burns and inflammation. A variety of substances in honey have been suggested as the key component to its antimicrobial potential; polyphenolic compounds, hydrogen peroxide, methylglyoxal and bee-defensin 1. These components vary greatly across honey samples due to botanical origin, geographical location and the individual bee. The use of medical grade honey, Medihoney and Revamil, in the treatment of surface wounds and burns has been seen to improve the healing process, reduce healing time, reduce scarring and prevent microbial contamination. Therefore, medical grade honeys should be used for these treatments and reduce the demand for antibiotic usage. In this review, we aim to outline the constituents of honey and how they affect the antibiotic potential of honeys in a clinical setting.
ARTICLE | doi:10.20944/preprints202306.0257.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: wound dressing; drug delivery; organ culture, infection models, ciprofloxacin, infected wounds
Online: 5 June 2023 (08:09:29 CEST)
Bacterial infections are a constant challenge in the management of acute and chronic wounds. Chronic wounds, like diabetic foot ulcers, have increased significantly in the last years due to the rise of an aging population. A better understanding of the infectious pathophysiological mechanisms is urgently needed along with new options for the treatment of wound infections and wound healing disorders. New advances in the preparation of biocompatible dressing materials that can be loaded with antimicrobial drugs may improve the topical treatment of infected wounds. In this study, we investigated the antimicrobial activity of polyvinylpyrrolidone (PVP) foils loaded with ciprofloxacin (Cipro-foils) in the presence of acetic acid as co-solvent. We used ex vivo human wounds that were infected with two bacterial strains: Methicillin-Resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa (PAO1). The effectiveness of the treatment was demonstrated by the quantification of the living bacteria extracted from the wound and the detection of released immunological mediators in skin extracts and in the skin culture media. We found that Cipro-foils effectively treated the infection with both PAO1 and MRSA. Other than PAO1, MRSA had not proteolytic effects. MRSA infections increased cytokines expression and release. Interestingly, treatment with Cipro-foils could partially counteract these effects.
REVIEW | doi:10.20944/preprints202211.0170.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: wound healing; inflammation; microenvironment; stem cells; extracellular matrix; hypoxia; growth factors
Online: 9 November 2022 (03:41:12 CET)
Based on its large surface area and covering the whole human body, the skin body’s largest organ and its main function is protection. Injuries and wound healing involving the skin offer valuable lessons shared with and of relevance to other organ systems and the diseases that impact them. Arguably the most complex human body process, wound healing is a multifaceted process that involves multiple cells and the extracellular matrix (ECM), with each component playing a specific role in the different stages of the healing process. Importantly, studies indicate that cells with stem cell-like properties are present within many of the human tissues and play key roles in case of tissue and cellular injury. Cell-to-cell and cell-to-ECM interactions are salient in wound healing subsequent to an injury. Microenvironment related factors and the variations therein including hypoxia or the abundance of oxygen, the presence/absence of growth factors and cytokines add to the complexity of the wound healing process and impact cell function and result in compromised or enhanced wound healing. This expert review critically examines the advances in biochemical and analytical tools that are enable the analysis of numerous cells and molecules within the wound microenvironment, revealing great cellular heterogeneity as well as novel molecular targets of importance to enhance wound healing. In a broader angle, we emphasize the ways in which wound healing is significant in the search for perfect skin after injury and in many common complex human diseases including cancer. In all, wound healing is a centrepiece of integrative biology research and applications in medicine as well as dermatology as discussed in this review.
CASE REPORT | doi:10.20944/preprints202210.0422.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Breast Augmentation; Reduction Mammoplasty; non-healing surgical wound; Wharton's jelly allograft
Online: 27 October 2022 (07:56:25 CEST)
Nearly 15 million patients undergo cosmetic surgery in the United States each year, with breast augmentations such as implants, lifts, or reductions being some of the most common procedures. The most common complications of these procedures are scarring and infection at the incision site, which often necessitates expensive corrective surgery. After significant weight loss, the patient in this study underwent an elective lower body lift in conjunction with a breast reduction and nipple-areolar transplant. An autologous skin graft was used at the transplant donor site. The skin graft unfortunately necrosed, warranting the need for rapid wound closure to avoid further pain and infection. The patient was treated for eight weeks with conservative measures. After eight weeks of failed attempts to close her wound, she was referred for specialist care. Upon initial examination, the donor site wound measured 3.5 cm x 3.5 cm with no sign of epithelialization. The patient received a single dose of Wharton’s jelly flowable perinatal tissue allograft and five hyperbaric oxygen therapy treatments over seven weeks. Upon inspection at the final examination, the wound was closed entirely with 100% epithelialization overlying granulation tissue. This case study demonstrates a precedent for the application of Wharton’s jelly flowable allografts in complicated cosmetic post-surgical wounds. Future efforts will be directed at applying Wharton’s jelly allografts on a preventative basis. Preventative applications could be in stage 2 pressure sores or intra-operatively to decrease potential patient suffering, prevent emotional distress, and reduce unnecessary healthcare expenses.
ARTICLE | doi:10.20944/preprints202107.0540.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: polymeric spiral-wound membrane; microfiltration; transmembrane pressure; diafiltration; micellar casein concentrate
Online: 23 July 2021 (11:05:17 CEST)
Micellar Casein Concentrate (MCC) is manufactured from microfiltration (MF) of skim milk utilizing ceramic or polymeric membrane filtration. While ceramic filtration has higher efficiency, use of polymeric is cost effective and the process is familiar to several US dairy processors. The aim of the present study was to develop an optimized membrane filtration process to produce MCC using spiral wound polymeric membrane filtration (SW MF) system by systematic selection of transmembrane pressure (TMP) and level of diafiltration (DF). Using skim milk as feed material, preliminary lab-scale MF experiments were conducted using 0.5 µm polyvinylidene fluoride (PVDF) membrane. Three TMP (34.5, 62.1, and 103.4 kPa) and three levels of DF (70, 100, and 150%) along with a process without DF as control were used in the study. Effect of TMP and effectiveness of DF on flux rates, SP removal, casein to total protein (CN/TKN) ratio, casein to true protein (CN/TP) ratio, rejection of casein (rej CN) and SP (rej SP) were evaluated. At all TMP values used in the study, the overall flux (O Flux) increased with the level of DF. Highest O Flux of 30.77 liter per meter square per hour (LMH) was obtained with 34.5 kPa pressure and 150% DF. The impact of DF was more pronounced at lower pressures than at the higher pressures used in the study. With controlled DF, instantaneous flux was maintained within 80% of initial flux for the entire process run. For all the experiments, casein has a rejection of 0.97 to 1.0, while serum protein has the lowest rejection of 0.10 at 34.5 kPa pressure and 150% DF level. Use of 34.5 kPa and DF level of 150 % contributed to 81.45% SP removal, and casein to true protein ratio of 0.96. SP removal data from the lab-scale experiments were fitted into a mathematical model using DF and square of TMP as factors. The model predicts SP removal within 90-95% of actual SP removal got from the pilot plant experiments.
REVIEW | doi:10.20944/preprints202103.0229.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: skin regeneration; wound healing; skin stem cells; skin vascularization; 3D printing.
Online: 8 March 2021 (15:26:04 CET)
In the past decades, regenerative medicine applied on skin lesions has been a field of constant improvement for both human and veterinary medicine. The process of healing cutaneous wound injuries implicates a well-organized cascade of molecular and biological processes. However, sometimes the normal process fails and can result in a chronic lesion. In addition, wounds are considered an increasing clinical impairment, due to the progressive ageing of the population, as well as the prevalence of concomitant diseases, such as diabetes and obesity, that represent risk aggravating factors for the development of chronic skin lesions. Stem cells regenerative potential has been recognized worldwide, including towards skin lesion repair, Tissue engineering techniques have long been successfully associated with stem cell therapies, namely the application of 3D bioprinted scaffolds. With this review we intend to explore several stem cell sources with promising aptitude towards skin regeneration, as well as different techniques used to deliver those cells and provide a supporting extracellular matrix environment, with effective outcomes. Furthermore, different studies are discussed, both in vitro and in vivo, towards their relevance in the skin regeneration field.
REVIEW | doi:10.20944/preprints201805.0378.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: annexins; inflammation; wound healing; host-pathogen interplay; drug target; translational research
Online: 27 May 2018 (11:32:34 CEST)
The vertebrate annexin superfamily (AnxA) consists of 12 members of a calcium (Ca2+) and phospholipid binding protein family which share a high structural homology. In keeping with this hallmark feature, annexins have been implicated in the Ca2+-controlled regulation of a broad range of membrane events. In this review, we identify and discuss several themes of annexin actions that hold a potential therapeutic value, namely the regulation of the immune response and the control of tissue homeostasis, and that repeatedly surface in the annexin activity profile. Our aim is to identify and discuss those annexin properties which might be exploited from a translational science and specifically clinical point of view.
ARTICLE | doi:10.20944/preprints202311.1574.v1
Subject: Chemistry And Materials Science, Materials Science And Technology Keywords: textiles; modification; sustainable coatings; natural biodegradable polymers; alginate fibers; propolis; wound dressings
Online: 24 November 2023 (07:35:38 CET)
The modification of cellulose woven fabrics and viscose nonwovens was carried out with the aim of preparing sustainable coatings from biodegradable natural polymers. The modification of fabrics with biodegradable natural polymers represents an ecological alternative to other textile modifications such as the sol-gel process. Coatings were prepared from erythritol, gelatin and collagen in various formulations with the addition of propolis and alginate fibers and a natural plasticizer (glycerin). The morphology of the materials was determined before and after modification with Dino-lite, the pH value, the drop test method, the angle recovery angle, the thickness and the mass per unit area. The modifications have no significant effect on the thickness and mass per unit area, in a larger proportion they show hydrophilic properties, which favours the application for medical purposes - for example the absorption of exudates, wound dressings etc. Due to the neutral and slightly alkaline pH value of the modified samples, they are suitable for external application on the skin. The recovery angle of the modified samples proves that the samples do not tend to crease and that they retain their elasticity after modification and have a pleasant textile feel (fabric hand).
ARTICLE | doi:10.20944/preprints202311.1391.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: endophytes; antimicrobial; antibiofilm; wound dressings; antibacterial additives; natural products; Staphylococcus aureus; MRSA
Online: 22 November 2023 (05:51:03 CET)
The wound management sector has attracted considerable attention due to the increasing challenge posed by antimicrobial resistance (AMR) and the specialized care required for chronic wounds. Effective wound care involves selecting appropriate dressings tailored with antimicrobial agents to prevent bacterial infection. Among various types of wound dressings, fibers and electrospun fibers, with their unique characteristics, have emerged as innovative new materials. However, the rise of AMR necessitates the exploration of new antimicrobial agents for wound dressings, particularly for addressing bacterial pathogens like methicillin-resistant Staphylococcus aureus (MRSA). Endophytic fungi, known for producing diverse bioactive compounds, including novel antibacterial agents, represent a promising source of such new agents. This study tested thirty-two endophytic fungi from thirteen distinct Australian native plants for their antibacterial activity against S. aureus, the most common wound-associated bacteria. Ethyl acetate (EtOAc) extracts from fungal culture filtrates exhibited inhibitory effects against both methicillin-sensitive S. aureus ATCC 25923 and MRSA strains M173525 and M180920. DNA sequence analysis was employed for fungal identification, with EtOAc extracts from the most active sample, EL 19 (Chaetomium globosum), selected for further bactericidal and antibiofilm testing against the chosen bacteria. Biofilm of S. aureus ATCC 25923 was reduced by 55% by EtOAc extracts of EL 19 at 1/2 × MIC. To demonstrate the potential application in wound dressing materials, three different concentrations of the extract were incorporated into Polycaprolactone fiber mats through electrospinning, with resultant inhibition of S. aureus ATCC 25923 being observed. This research underscores the potential of endophytic fungi from Australian plants as sources of substances effective against common wound pathogens. Further exploration of the responsible compounds and their mechanisms could facilitate the development of wound dressings effective against MRSA and innovative biofilm-resistant electrospun fibers, contributing to the global efforts to combat AMR.
ARTICLE | doi:10.20944/preprints202301.0150.v2
Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: oral; mucosa; mucins; tight junctions; wound-healing; E-liquids; cytotoxicity; viability; confluency.
Online: 3 April 2023 (03:33:37 CEST)
Background: Expansion of OKF6/TERT-2 oral epithelial cells in vitro is important for studying the molecular biology of disease and pathology affecting the oral cavity. Keratinocyte Serum-Free Medium (KSFM) is the medium of choice for this cell line. This study compares three media for OKF6/TERT-2 cultures: KSFM, Dulbecco’s Modified Eagle Medium/Nutrient Mixture of Hams F-12 (DMEM/F12) and a composite medium comprised of DMEM/F-12 and KSFM (1:1 v/v), referred as DFK. The toxicological effects of electronic cigarette liquids (E-liquids) on OKF6/TERT-2 cells cultured in these media were also compared. Methods: Cells were cultured in KSFM, DMEM/F12 or DFK and cellular morphology, growth, wound healing and gene expression of mucins and tight junctions were evaluated. Additionally, cytotoxicity was determined after E-liquid exposures. Results: Switching from KSFM to DMEM/F12 or DFK 24-hours post-seeding leads to typical cellular morphologies, and these cultures reach confluency faster than those in KSFM. Wound-healing recovery occurred fastest in DFK. Except for claudin-1, there is no difference in expression of the other genes tested. Additionally, E-liquid cytotoxicity appears to be amplified in DFK cultures. Conclusions: DMEM/F12 and DFK are alternative media for OKF6/TERT-2 cell culture to study molecular biology of disease and pathology, provided cells are initially seeded in KSFM.
REVIEW | doi:10.20944/preprints202212.0108.v1
Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: Dendrimer; biomaterial; cell scaffold; hydrogel; wound repair; adhesion; differentiation; osseointegration.; hydroxyapatite; scaffold
Online: 7 December 2022 (01:57:27 CET)
The capability of radially polymerized bio-dendrimers and hyperbranched polymers for medical applications is well established. Among them, perhaps the most important are those that involve interactions with the regenerative mechanisms of cells. Dendritic polymers due to their distinctive architecture may play a multitude of roles such as protein biomimicry (collagen, elastin, hydroxy apatite production), gene and drug delivery (cell differentiation, antimicrobial protection), surface chemistry and charge modulation (adhesion to cells and tissues), polymer cross-linking (eye, skin and internal organ wound healing). The review highlights all the different categories of hard and soft tissues that may be remediated with their contribution. The reader will be also exposed to the incorporation methods to established biomaterials such as scaffolds, the functionalization strategies, and the synthetic paths for the assembly from biocompatible building blocks and natural metabolites.
ARTICLE | doi:10.20944/preprints202211.0119.v1
Subject: Chemistry And Materials Science, Surfaces, Coatings And Films Keywords: biodegradable polymer nanosheets; wound healing; laser ablation in liquid; nanoparticles; ZnO; ZnCl2
Online: 7 November 2022 (11:20:14 CET)
So far, poly(L-lactic acid), PLLA, nanosheets proved to be promising for wound healing. Such biodegradable materials are easy-to-prepare, bio-friendly, cost-effective, simple to apply and were shown to protect burn wounds and facilitate their healing. At the same time, certain metal ions are known to be essential for wound healing, which is why this study was motivated by the idea of incorporating PLLA nanosheets with Zn2+ ion containing nanoparticles. Upon being applied on wound, such polymer nanosheets should release Zn2+ ions, which is expected to improve wound healing. The work thus focused on preparing PLLA nanosheets embedded with several kinds of Zn-containing nanoparticles, their characterization and ion-release behavior. ZnCl2 and ZnO nanoparticles were chosen as model particles with different solubility in water, both types showing similar ion release dynamics in liquid medium with pH around 7.4.
REVIEW | doi:10.20944/preprints202104.0652.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: Enzymatic reaction; crosslinking; Hydrogel; Biomedical application; Tissue engineering; Wound healing; Drug delivery
Online: 26 April 2021 (10:52:24 CEST)
Self-assembled structures mostly arises through enzyme-regulated phenomena in nature under persistent conditions. Enzymatic reactions are one of main biological processes in fabrication and construction of supramolecular hydrogel networks required for biomedical applications. The enzymatic processes provide a unique opportunity to integrate hydrogel formation. In most of cases, structure and substrates of hydrogels are adjusted by enzyme catalysis due to the chemo-, regio- and stereo-selectivity of enzymes. Hydrogels processed by using various enzyme schemes showed remarkable characteristics as dynamic frames for cells, bioactive molecules and drugs in biomedical applications. A novel class of enzyme-mediated crosslinking hydrogels mimics the extracellular matrices by displaying unique physicochemical properties and functionalities like water-retention capacity, drug loading ability, biodegradability, biocompatibility, biostability, bioactivity, optoelectronic properties, self-healing ability, shape memory ability. In recent years, many enzymatic systems investigated hydrogel cross-linking. Results of biocompatible hydrogel products show that these mechanisms of crosslinking can fulfill requirements for variety of biomedical applications including tissue engineering, wound healing and drug delivery.
REVIEW | doi:10.20944/preprints202102.0449.v1
Subject: Chemistry And Materials Science, Materials Science And Technology Keywords: multifunctional; hydrogel nanocomposties; tissue engineering; drug delivery; wound healing; bioprinting; biowearable devices
Online: 22 February 2021 (08:48:20 CET)
Hydrogels are used for various biomedical applications due to their biocompatibility, capacity to mimic the extracellular matrix, and ability to encapsulate and deliver cells and therapeutics. However, traditional hydrogels have a few shortcomings, especially regarding their physical properties, thereby limiting their broad applicability. Recently, researchers have investigated the incorporation of nanoparticles (NPs) into hydrogels to improve and add to the physical and biochemical properties of hydrogels. This brief review focuses on papers that describe the use of nanoparticles to improve more than one property of hydrogels. Such multifunctional hydrogel nanocomposites have enhanced potential for various applications, including tissue engineering, drug delivery, wound healing, bioprinting and biowearable devices.
REVIEW | doi:10.20944/preprints202011.0053.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Mast cells; innate immunity; adaptive immunity; wound healing; Immunoglobin E; vaccine adjuvants
Online: 2 November 2020 (14:59:10 CET)
Mast cells are long-lived, granular, myeloid-derived leukocytes that have significant protective and repair functions in tissues. Mast cells sense disruptions in the local microenvironment and are first responders to physical, chemical and biological insults. When activated, mast cells release growth factors, proteases, chemotactic proteins and cytokines thereby mobilizing and amplifying the innate and adaptive immune system. Mast cells are therefore significant regulators of homeostatic functions and may be essential in microenvironmental changes during pathogen invasion and disease. During infection by helminths, bacteria and viruses, mast cells release antimicrobial factors to facilitate pathogen expulsion and eradication. Mast cell-derived proteases and growth factors protect tissues from insect/snake bites and exposure to ultraviolet radiation. Finally, mast cells release mediators that promote wound healing in the inflammatory, proliferative and remodeling stages. Since mast cells have such a powerful repertoire of functions, targeting mast cells may be an effective new strategy for immunotherapy of disease and design of novel vaccine adjuvants. In this review, we will examine how certain strategies that specifically target and activate mast cells can be used to treat and resolve infections, augment vaccines and heal wounds. Although these strategies may be protective in certain circumstances, mast cells activation may be deleterious if not carefully controlled and any therapeutic strategy using mast cell activators must be carefully explored.
ARTICLE | doi:10.20944/preprints202304.1001.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: Eclipta prostrata; gelatin; foam dressing; wound dressing; physical property; absorption; dehydration; pH environment
Online: 26 April 2023 (15:23:50 CEST)
Developing novel wound dressings containing medicinal plant extracts can have several potential benefits, including improving the therapeutic value of the dressings and reducing the cost of producing wound dressings. In this study, we prepared foam dressing containing Eclipta prostrata leaf extract and gelatin (Eclipta prostrata dressing). Chemical composition was verified using Fourier transform infrared spectroscopy (FTIR), and pore structure was obtained by scanning electron microscopy (SEM). The physical properties, including absorption and dehydration properties, were also evaluated. The chemical properties were measured to determine the pH environment after being submerged with Eclipta prostrata dressings. The results revealed that the Eclipta prostrata dressing had a pore structure with an appropriate pore size (313.25 ± 76.51 µm and 383.26 ± 64.45 µm for the Eclipta prostrata A and Eclipta prostrata B dressings, respectively). The Eclipta prostrata B dressing was more consistent porosity, resulting in a higher absorption capacity and faster dehydration rate. According to physical properties, the Eclipta prostrata B dressing is best used on low-exuding wounds. Furthermore, the Eclipta prostrata A and B dressings make a slightly acidic environment. Therefore, our foam dressing will not interfere wound healing process.
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: DPTM; Methicillin-resistant Staphylococcus aureus (MRSA); Antibacterial activity; Murine skin wound model; MIC
Online: 12 April 2021 (12:18:08 CEST)
Staphylococcus aureus (S. aureus) is a major human pathogen that requires new antibiotics with unique mechanism. A new pleuromutilin derivative, 14-O-[(4,6-Diaminopyrimidine-2-yl) thioacetyl] mutilin (DPTM), has been synthesized and proved as a potent antibacterial agent using in vitro and in vivo assays. In the present study, DPTM was further in vitro evaluated against Methicillin-resistant Staphylococcus aureus (MRSA) isolated from dairy farms and outperformed tiamulin fumarate, a pleuromutilin drug used for veterinary. Moreover, a murine skin wound model caused by MRSA infection was established and the healing effect of DPTM was investigated. The results showed that DPTM could promote the healing of MRSA skin infection, reduce the bacterial burden of infected skin MRSA and decrease the secretion of IL-6 and TNF-α inflammatory cytokines in plasma. These results provided the basis for further in-depth drug targeted studies of DPTM as a novel antibacterial agent.
REVIEW | doi:10.20944/preprints202305.1664.v1
Subject: Medicine And Pharmacology, Surgery Keywords: Soft tissue; necrotizing infection; water borne; vibrio; fungal; aeromonas; debridement; negative pressure wound care
Online: 23 May 2023 (14:43:28 CEST)
Background: Skin and soft tissue infections (SSTI) are common presentations to the emergency department. However, this is less common after contact with contaminated water, both salt or fresh. This review presents the diagnosis and the management of water-related soft tissue sepsis in this vulnerable and difficult to treat subgroup of necrotizing soft tissue sepsis. Methods: A summative literature overview regarding bacterial and fungal SSTI after contact with contaminated water, with practical diagnostic and management aspects addressed. Results: The literature indicates that these remain difficult to treat wounds and organisms. An approach using appropriate diagnostic tools with both medical and surgical management strategies is provided. Conclusion: SSTI due to water contamination of wounds involve unusual organisms with unusual resistance patterns and require a nuanced and directed diagnostic approach with adaptation of the normal antibiotic or antifungal selection to achieve cure, along with aggressive debridement and wound care.
ARTICLE | doi:10.20944/preprints202009.0703.v1
Subject: Chemistry And Materials Science, Analytical Chemistry Keywords: açaí; total polyphenol; total anthocyanin; antioxidant; elemental analysis; essential elements; biological activity; wound healing
Online: 29 September 2020 (09:14:48 CEST)
Chemical composition analysis of açaí extracts revealed higher levels of total polyphenol content in purple açaí samples for both commercial (4.3 – 44.7 gallic acid equivalents mg/g) and non-commercial samples (30.2 – 42.0 mg/g) compared to white (8.2 – 11.9 mg/g) and oil samples (0.8 – 4.6 mg/g). The major anthocyanin compounds found in purple açaí samples were cyanidin-3-glucoside and cyanidin-3-rutinoside with total concentrations in the range of 3.6 – 14.3 cyanidin-3-glucoside equivalents mg/g. The oligomeric proanthocyanidins were quantified in the range of 1.5 – 6.1 procyanidin B1 equivalents mg/g. Moreover, açaí presented significant levels of calcium, magnesium, manganese, iron, zinc and copper, essential minor and trace elements, in comparison with other berries. All of the açaí extracts at 50 μg/mL potently inhibited the release of reactive oxygen species in lipopolysaccharide-stimulated RAW 264.7 macrophage cells, but none inhibited the release of nitric oxide. Furthermore, all the açaí samples demonstrated potential as wound healing agents due to the high levels of migration activity in human fibroblast cells.
ARTICLE | doi:10.20944/preprints201801.0100.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: intra-abdominal pressure; abdominal compartment syndrome; pressure sensor; negative pressure wound therapy; open abdomen;
Online: 11 January 2018 (09:17:10 CET)
1) Introduction: Negative pressure wound therapy (NPWT) is a frequently applied open abdomen (OA) treatment. There are only a few experimental data supporting this method and describing the optimal settings and pressure distribution in the abdominal cavity during this procedure. The aim of our study was to evaluate pressure values at different points of the abdominal cavity during NPWT in experimental abdominal compartment syndrome (ACS) animal model. 2) Methods: In this study (permission Nr. 13/2014/UDCAR) 27 Hungahib pigs (15.4- 20.2 kg) were operated. ACS was generated by implanting a plastic bag in the abdomen through mini-laparotomy and filled with 2100- 3300 ml saline solution (37 C°) to an intraabdominal pressure (IAP) of 30 mmHg. After 3 hours, NPWT (Vivano Med ® Abdominal Kit, Paul Hartmann AG, Germany) or Bogota bag was applied. NPWT group was divided into -50, -100 and 150 mmHg suction group. Pressure distribution to the abdominal cavity was monitored at 6 different points of the abdomen via a multichannel pressure monitoring system. 3) Results: The absolute pressure levels were significantly higher above than below the layer. The values of the pressure were similar in the midline than laterally. Amongst the bowels, the pressure values changed periodically between 0 and -12 mmHg which might be caused by the peristaltic movements. 4) Conclusions: The porcine model of the present study seems to be well applicable for investigating ACS and NPWT. It was possible to provide valuable for clinicians. The pressure was well distributed by the protective layer to the lateral parts of the abdomen and this phenomenon did not change considerably during the therapy.
REVIEW | doi:10.20944/preprints201712.0186.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: cardiovascular diseases; atherosclerosis; oxidative stress; angiogenesis and arteriogenesis; endothelial dysfunction; growth hormone; IGF-I; wound healing
Online: 26 December 2017 (10:30:09 CET)
This review describes the positive effects of growth hormone on the cardiovascular system. We analyze why the vascular endothelium is a real internal secretion gland, whose inflammation is the first step for developing atherosclerosis, as well as the mechanisms by which GH acts on the vascular endothelium improving its dysfunction. We also report how GH acts on coronary arterial disease and heart failure, and on peripheral arterial disease inducing the generation of new collateral vessels able to bypass a major artery occlusion. We include some preliminary data from a trial in which GH or placebo is given to elder people suffering from critical limb ischemia, showing the effects of the hormone on plasma markers of inflammation, and stating that the administration of GH in short periods of time is safe and effective even in diabetic patients. We also analyze how Klotho may have strong relationships with GH, inducing, after being released from the damaged vascular endothelium, the pituitary secretion of GH to repair the damaged tissue. Lastly, we show how GH induces wound healing by increasing the blood flow to the ischemic tissue. In summary, we postulate that short-time GH administration is useful for treating cardiovascular diseases.
CASE REPORT | doi:10.20944/preprints202311.1995.v2
Subject: Medicine And Pharmacology, Surgery Keywords: vertical rectus abdominis muscle flap; perineal wound; pelvic exenteration; squamosal cell carcinoma of the uterine cervix; reconstruction
Online: 1 December 2023 (10:46:42 CET)
Due to the still large number of patients diagnosed with pelvic neoplasms (colorectal, gynecological, and urological) in advanced stages right from the initial diagnosis, surgery represents the mainstay of treatment, often implying wide, eventually multi-organ resections in order to achieve negative surgical margins. Perineal wound morbidity, particularly in extralevator abominoperineal excision, leads to complications and local infection rates of up to 40%. Strategies to reduce postoperative wound complications are pursued to address this issue.The VRAM flap remains the gold standard for autologous reconstruction after pelvic oncological resection; it was initially designed for abdominal wall defects and later expanded for large pelvic tissue defects.The flap's application is based on its physical characteristics, including abundant tissue and a generous skin paddle, which effectively obliterates dead space after exenterations. The generous skin paddle offers good cosmetic and functional outcomes at the recipient site.This article describes the case of a patient histopathologically diagnosed with stage IIIA squamous cell carcinoma of the uterine cervix who received multimodal onco-surgical treatment. The surgical mainstay of this treatment is pelvic exenteration. Pelvic reconstruction after this major surgery was performed using a vertical flap with the rectus abdominis.