Cutaneous Wound Healing Research Articles

A therapeutic role of exosomal lncRNA H19 from adipose mesenchymal stem cells in cutaneous wound healing by triggering macrophage M2 polarization

BackgroundEmerging evidence has figured out that adipose mesenchymal stem cells (ADSCs) promote wound healing. Exosomes, which act as main paracrine factors and contains various protein, lncRNA, and miRNAs, play a critical role in wound healing. Nevertheless, the mechanism remains to be elucidated. This study aims to identify the underlying mechanism of ADSCs-derived exosome (ADSCs-exos)-mediated wound healing. MethodsADSCs-exos were characterized using the transmission electron microscope, dynamic light scattering, and western blot. ELISA, RT-qPCR, flow cytometry, western blot, CCK-8 assay, transwell assay and tube formation were employed to validate the actions of ADSCs-exos harboring H19 in cell polarization, proliferation, migration and angiogenesis. The regulatory axis among H19, miR-130b-3p and PPARγ or STAT3 was confirmed by RNA pull-down, RIP assay and dual-luciferase reporter assays. ResultsADSCs-exos harboring H19 promoted macrophage M2 polarization, thereby enhancing fibroblast proliferation, migration and endothelial cell angiogenesis. However, their promotive effects were disrupted within H19 depletion in ADSCs-exos. Additionally, miR-130b-3p, directly targeting PPARγ or STAT3, was identified to be a downstream effector to participate in H19-mediated biological effects. Moreover, ADSCs-exos carrying H19 modulated cutaneous wound healing via H19/miR-130b-3p -mediated macrophage M2 polarization in vivo. ConclusionCollectively, ADSCs-derived exosomal H19 accelerates cutaneous wound healing via the miR-130b-3p/PPARγ/STAT3 axis, indicating potential therapeutic strategies for the treatment of wound healing.

Notoginsenoside R1 Facilitates Cell Angiogenesis by Inactivating the Notch Signaling During Wound Healing.

The development of chronic, nonhealing wounds is a persistent medical problem that drives patient morbidity and increases healthcare costs. Angiogenesis is a critical accompanying activity in the proliferation stage during the wound healing process. Notoginsenoside R1 (NGR1) isolated from Radix notoginseng has been reported to alleviate diabetic ulcers by promoting angiogenesis and decreasing inflammatory responses and apoptosis. In the present study, we investigated the effect of NGR1 on angiogenesis and its therapeutic functions in cutaneous wound healing. For in vitro evaluation, cell counting kit-8 assays, migration assays, Matrigel-based angiogenic assays, and western blotting were conducted. The experimental results showed that NGR1 (10-50 μM) had no cytotoxicity to human skin fibroblasts (HSFs) and human microvascular endothelial cells (HMEC), and NGR1 treatment facilitated the migration of HSFs and enhanced angiogenesis in HMECs. Mechanistically, NGR1 treatment inhibited the activation of Notch signaling in HMECs. For in vivo analysis, hematoxylin-eosin staining, immunostaining, and Masson's trichrome staining were performed, and we found that NGR1 treatment promoted angiogenesis, reduced wound widths, and facilitated wound healing. Furthermore, HMECs were treated with N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT; a Notch inhibitor), and DAPT treatment was found to exert pro-angiogenic effects. Simultaneously, DAPT was administrated into experimental cutaneous wound healing model, and we found that DAPT administration prevented the development of cutaneous wounds. Collectively, NGR1 promotes angiogenesis and wound repair via activation of the Notch pathway and exhibits therapeutic effects on cutaneous wound healing.

Mechano-biological and bio-mechanical pathways in cutaneous wound healing.

Injuries to the skin heal through coordinated action of fibroblast-mediated extracellular matrix (ECM) deposition, ECM remodeling, and wound contraction. Defects involving the dermis result in fibrotic scars featuring increased stiffness and altered collagen content and organization. Although computational models are crucial to unravel the underlying biochemical and biophysical mechanisms, simulations of the evolving wound biomechanics are seldom benchmarked against measurements. Here, we leverage recent quantifications of local tissue stiffness in murine wounds to refine a previously-proposed systems-mechanobiological finite-element model. Fibroblasts are considered as the main cell type involved in ECM remodeling and wound contraction. Tissue rebuilding is coordinated by the release and diffusion of a cytokine wave, e.g. TGF-β, itself developed in response to an earlier inflammatory signal triggered by platelet aggregation. We calibrate a model of the evolving wound biomechanics through a custom-developed hierarchical Bayesian inverse analysis procedure. Further calibration is based on published biochemical and morphological murine wound healing data over a 21-day healing period. The calibrated model recapitulates the temporal evolution of: inflammatory signal, fibroblast infiltration, collagen buildup, and wound contraction. Moreover, it enables in silico hypothesis testing, which we explore by: (i) quantifying the alteration of wound contraction profiles corresponding to the measured variability in local wound stiffness; (ii) proposing alternative constitutive links connecting the dynamics of the biochemical fields to the evolving mechanical properties; (iii) discussing the plausibility of a stretch- vs. stiffness-mediated mechanobiological coupling. Ultimately, our model challenges the current understanding of wound biomechanics and mechanobiology, beside offering a versatile tool to explore and eventually control scar fibrosis after injury.

GelMA Hydrogel Loaded with Extracellular Vesicles Derived from Umbilical Cord Mesenchymal Stem Cells for Promoting Cutaneous Diabetic Wound Healing.

Chronic diabetic wounds have become a significant cause of disability worldwide. It is highly desired to develop effective therapies that can promote the rapid healing of diabetic wounds. Owing to the outstanding hydrophilic and water-retaining properties, hydrogels could accelerate the healing process. Extracellular vesicles (EVs) have shown the ability to promote cell regeneration and angiogenesis. In this study, we chose a gelatin methacryloyl (GelMA) hydrogel, a kind of biomaterial characteristic of good biocompatibility, to load the EVs derived from umbilical cord mesenchymal stem cells (UCMSCs) in order to have a long-lasting effect by consistent release of EVs. Then, the hydrogel with EVs was used to treat diabetic wounds in rat models. Nuclear magnetic resonance spectroscopy and scanning electron microscopy were used to characterize the synthesis of the hydrogel; cell experiments, animal experiments, and histological staining were used to evaluate the function of the hydrogel with EVs. The results show that the GelMA hydrogel incorporated with the UCMSC-derived EVs exhibits unique physicochemical properties, excellent biocompatibility, and much enhanced therapeutic effects for diabetic wounds.

Topical formulation containing chitosan-chamomile microparticles in cutaneous wound healing in rats

Objective: The aim of this research was to evaluate the efficacy of a topical formulation containing chitosan-chamomile microparticles in cutaneous healing in rats. Method: Male Wistar rats (n=57) were randomly distributed into three groups: treatment; vehicle; and control. Evaluations were performed on days 2, 7 and 14 after the surgical procedure using skin lesion photography, and histological and biochemical analyses. Results: The results showed that there was no difference in the healing index and in the histological analysis of the inflammatory infiltrate among groups. Fibrogenesis was more significant in the group treated with the test formulation at day 7, and angiogenesis was greater in the vehicle and chamomile groups at day 2. The quantification of hydroxyproline showed a higher amount of collagen in the group treated with chamomile, mainly at day 14, although the histological quantification of collagen showed no difference between the groups. Conclusion: From the results of this study, it can be concluded that the formulation, although it had no effect on the healing time, improved the quality of the cicatricial tissue formed with a greater quantity of fibroblasts and collagen.

Topical formulation containing chitosan-chamomile microparticles in cutaneous wound healing in rats

Objective: The aim of this research was to evaluate the efficacy of a topical formulation containing chitosan-chamomile microparticles in cutaneous healing in rats. Method: Male Wistar rats (n=57) were randomly distributed into three groups: treatment; vehicle; and control. Evaluations were performed on days 2, 7 and 14 after the surgical procedure using skin lesion photography, and histological and biochemical analyses. Results: The results showed that there was no difference in the healing index and in the histological analysis of the inflammatory infiltrate among groups. Fibrogenesis was more significant in the group treated with the test formulation at day 7, and angiogenesis was greater in the vehicle and chamomile groups at day 2. The quantification of hydroxyproline showed a higher amount of collagen in the group treated with chamomile, mainly at day 14, although the histological quantification of collagen showed no difference between the groups. Conclusion: From the results of this study, it can be concluded that the formulation, although it had no effect on the healing time, improved the quality of the cicatricial tissue formed with a greater quantity of fibroblasts and collagen.

Engineered BMSCs-Derived Exosomal miR-542-3p Promotes Cutaneous Wound Healing.

The healing of cutaneous wounds requires better strategies, which remain a challenge. Previous reports indicated that the therapeutic function of mesenchymal stem cells is mediated by exosomes. This work demonstrated the regenerative effects of engineered BMSCsderived Exosomal miR-542-3p in skin wound mouse models. Bone marrow mesenchymal stem cells (BMSCs) -derived exosomes (BMSCs-Exos) were isolated by ultracentrifugation and identified by Transmission Electron Microscope (TEM) and Nanoparticle Tracking Analysis (NTA). BMSCs-Exo was loaded with miRNA-542-3p by electroporation. We explored the effects of miRNA-542-3p-Exo on the proliferation and migration of Human Skin Fibroblasts (HSFs)/Human dermal microvascular endothelial cells (HMECs). In addition, The angiogenesis of HMECs was detected by Tube formation assay in vitro. The effects of miRNA-542-3p-Exo in the skin wound mouse model were detected by H&E staining, Masson staining, and immunofluorescence analysis. We assessed the effect of miRNA-542-3p-Exo on collagen deposition, new blood vessel formation, and wound remodeling in a skin wound mouse model. MiRNA-542-3p-Exos could be internalized by HSFs/HMECs and enhance the proliferation, migration, and angiogenesis of HSFs/HMECs in vitro and in vivo. The protein expression of collagen1/3 was significantly increased after miRNA-542-3p-Exo treatment in HSFs. In addition, the local injection of miRNA-542-3p-Exo promoted cellular proliferation, collagen deposition, neovascularization, and accelerated wound closure. This study suggested that miRNA-542-3p-Exo can stimulate HSFs/HMECs function. The treatment of miRNA-542-3p-Exo in the skin wound mouse model significantly promotes wound repair. The therapeutic potential of miRNA-542-3p-Exo may be a future therapeutic strategy for cutaneous wound healing.

PANX3 Channels Regulate Architecture, Adhesion, Barrier Function, and Inflammation in the Skin

The channel-forming glycoprotein PANX3 functions in cutaneous wound healing and keratinocyte differentiation, but its role in maintaining skin homeostasis through aging is not yet understood. We found that PANX3 is absent in newborn skin but becomes upregulated with age. We characterized the skin of global Panx3-knockout (KO) mice and found that KO dorsal skin showed sex differences at different ages but generally had reduced dermal and hypodermal areas compared with age-matched controls. Transcriptomic analysis of the KO epidermis revealed reduced E-cadherin stabilization and Wnt signaling compared with that of wild-type, consistent with the inability of primary KO keratinocytes to adhere in culture and diminished epidermal barrier function in KO mice. We also observed increased inflammatory signaling in the KO epidermis and a higher incidence of dermatitis in aged KO mice compared with that in wild-type controls. These findings suggest that during skin aging, PANX3 is critical in the maintenance of dorsal skin architecture, keratinocyte cell-cell and cell-matrix adhesion, and inflammatory skin responses.

Pharmacological Assessment of Cutaneous Wound Healing by Natural Apis Honey on Animal Models

Honey is a nutritional food with health-promoting properties. Antiseptics are topical agents that act to prevent growth of microorganisms. A range of Apis florea bee honey from Karnataka was used to investigate the prevention of infection and promote healing of wounds in rat models as honey is a tissue-regenerative agent. It contributes to all stages of wound healing, and thus has been used in direct topical application and also in dressings. Most honey samples with various dilutions have proved to possess, significant antibacterial potency against selected bacterial isolates by disc diffusion assay. The Coorg honey of Apis florea species showed highest antibacterial activity against Staphylococcus aureus (ATCC 6538) with 19.26±0.23 mm and the least susceptibility was recorded for bacterial strain Erwinia nigrifluens (ATCC 21922) with 8.97±0.48 mm. The Kolar honey of Apis florea species showed highest antibacterial activity against Bacillus cereus (ATCC 31443) with 8.79±0.16 mm and least susceptibility was recorded for Staphylococcus aureus (ATCC 6538) with 7.01±0.55 mm. The Bengaluru honey of Apis florea species showed highest antibacterial activity against Staphylococcus aureus (ATCC 6538) with 9.95±0.23 mm and least susceptibility was recorded for E.coli (ATCC 25891) with 6.27±0.22 mm. The present study also checked the wound healing ability of honey when applied topically in several rat models. The control rats were healed by 20 ± 1.07 days. The Kanamycin treated rats were healed on 10±1.45 days. 13 ±1.07days were recorded to heal the wounds by Apis florea honey samples of Abbe Falls, Coorg regions. 18 ±1.54 days and 17 ±1.03 days were recorded against Champion Reef regions of Kolar district and Varthur regions of Bengaluru district.

Dipotassium Glycyrrhizininate Improves Skin Wound Healing by Modulating Inflammatory Process.

Wound healing is characterized by a systemic and complex process of cellular and molecular activities. Dipotassium Glycyrrhizinate (DPG), a side product derived from glycyrrhizic acid, has several biological effects, such as being antiallergic, antioxidant, antibacterial, antiviral, gastroprotective, antitumoral, and anti-inflammatory. This study aimed to evaluate the anti-inflammatory effect of topical DPG on the healing of cutaneous wounds by secondary intention in an in vivo experimental model. Twenty-four male Wistar rats were used in the experiment, and were randomly divided into six groups of four. Circular excisions were performed and topically treated for 14 days after wound induction. Macroscopic and histopathological analyses were performed. Gene expression was evaluated by real-time qPCR. Our results showed that treatment with DPG caused a decrease in the inflammatory exudate as well as an absence of active hyperemia. Increases in granulation tissue, tissue reepithelization, and total collagen were also observed. Furthermore, DPG treatment reduced the expression of pro-inflammatory cytokines (Tnf-α, Cox-2, Il-8, Irak-2, Nf-kB, and Il-1) while increasing the expression of Il-10, demonstrating anti-inflammatory effects across all three treatment periods. Based on our results, we conclude that DPG attenuates the inflammatory process by promoting skin wound healing through the modulation of distinct mechanisms and signaling pathways, including anti-inflammatory ones. This involves modulation of the expression of pro- and anti-inflammatory cytokine expression; promotion of new granulation tissue; angiogenesis; and tissue re-epithelialization, all of which contribute to tissue remodeling.

Effects of exosomes derived from fibroblast cells on skin wound healing in Wistar rats

BackgroundThe role of exosomes in areas, such as skin wound healing, have been of consideratble interest recently. However, the effects of exosomes derived mainly from fibroblast cells on wound healing have yet to be documented well. The study aimed to evaluate the effects of exosomes derived from fibroblast cells on wound healing in Wistar rats. MethodsHuman fetal skin was isolated afterward centrifuge, and trypsin 0.1% was added to the cells after removing DPBS from the Falcon tube, and the trypsin was removed. The cells were moved to culture flasks. Then, the secondary culture of Human Fetal Skin Fibroblast was done. The pellets containing exosomes were suspended in PBS, and to achieve purified exosomes, the suspended Exosome were passed through a 0.22 µm filter. The exosome solution was kept at − 20 ºC. In the in vivo phase, 48 male Wistar rats were divided into four groups. Group I, low-dose exosome (LDE) solution (150 μl/day), group II high-dose exosome (HDE) solution (300 μl/day), group III commercially available ointment (positive control (PC)) was topically applied on wounds and group VI without treatment (negative control (NC)). A skin biopsy was taken for histopathological analysis. Wound area, depth of ulcer, degree of granulation, and inflammation were assessed. For histopathological assessment, re-epithelialization, inflammatory cells, granulation tissue, crust formation, and collagen maturation (fibrosis) parameters were evaluated. ResultsForty-eight male Wistar rats were included. The HDE group's showed accelerated healing compared to the NC and PC groups at 9 and 12 days. Inflammation and granulation were higher in the HDE, LDE, and PC groups than in the NC group (p < 0.05). The onset of re-epithelialization and collagen deposition was higher in the LDE, HDE, and PC groups, then on nine and 12-day, gradually maturing and extending through the ulcer (p < 0.05). On day 12, in almost all parameters, the LDE and HDE groups showed improved results compared to NC cases (p < 0.05). ConclusionsThe results showed that the utilization of fibroblast-Exo significantly promoted cutaneous wound healing in a rat full-thickness skin ulcer model. This is a potential innovation for cell-free therapy from fibroblast-Exo as a closed structure similar to human cells.

Liquid plasma as a treatment for cutaneous wound healing through regulation of redox metabolism

The skin functions as the outermost protective barrier to the internal organs and major vessels; thus, delayed regeneration from acute injury could induce serious clinical complications. For rapid recovery of skin wounds, promoting re-epithelialization of the epidermis at the initial stage of injury is essential, wherein epithelial keratinocytes act as leading cells via migration. This study applied plasma technology, which has been known to enable wound healing in the medical field. Through in vitro and in vivo experiments, the study elucidated the effect and molecular mechanism of the liquid plasma (LP) manufactured by our microwave plasma system, which was found to improve the applicability of existing gas-type plasma on skin cell migration for re-epithelialization. LP treatment promoted the cytoskeletal transformation of keratinocytes and migration owing to changes in the expression of integrin-dependent focal adhesion molecules and matrix metalloproteinases (MMPs). This study also identified the role of increased levels of intracellular reactive oxygen species (ROS) as a driving force for cell migration activation, which was regulated by changes in NADPH oxidases and mitochondrial membrane potential. In an in vivo experiment using a murine dorsal full-thickness acute skin wound model, LP treatment helped improve the re-epithelialization rate, reaffirming the activation of the underlying intracellular ROS-dependent integrin-dependent signaling molecules. These findings indicate that LP could be a valuable wound management material that can improve the regeneration potential of the skin via the activation of migration-related molecular signaling within the epithelial cell itself with plasma-driven oxidative eustress.

LncRNA MALAT1 Regulates Hyperglycemia Induced EMT in Keratinocyte via miR-205.

Epithelial-to-mesenchymal transition (EMT) is critical to cutaneous wound healing. When skin is injured, EMT activates and mobilizes keratinocytes toward the wound bed, therefore enabling re-epithelialization. This process becomes dysregulated in patients with diabetes mellitus (DM). Long non-coding RNAs (lncRNAs) regulate many biological processes. LncRNA-metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) influences numerous cellular processes, including EMT. The objective of the current study is to explore the role of MALAT1 in hyperglycemia (HG)-induced EMT. The expression of MALAT1 was found to be significantly upregulated, while the expression of miR-205 was downregulated in diabetic wounds and high-glucose-treated HaCaT cells. The initiation of EMT in HaCaT cells from hyperglycemia was confirmed by a morphological change, the increased expression of CDH2, KRT10, and ACTA2, and the downregulation of CDH1. The knockdown of MALAT1 was achieved by transfecting a small interfering RNA (SiRNA). MALAT1 and miR-205 were found to modulate HG-induced EMT. MALAT1 silencing or miR-205 overexpression appears to attenuate hyperglycemia-induced EMT. Mechanistically, MALAT1 affects HG-induced EMT through binding to miR-205 and therefore inducing ZEB1, a critical transcription factor for EMT. In summary, lncRNA MALAT1 is involved in the hyperglycemia-induced EMT of human HaCaT cells. This provides a new perspective on the pathogenesis of diabetic wounds.

Wound healing and microbiome, an unexpected relationship.

Skin wounds are common and represent a major public health and economical problem, with risks of complications and a significant negative impact on the quality of life of patients. Cutaneous wound healing is a tightly regulated process resulting in the restoration of tissue integrity. Wound healing involves the interaction of several skin, immune and vascular cells, growth factors and cytokines. However, external actors can play an important role in wound healing, such as the skin microbiome, which is the microbial commensal collection of bacteria, fungi and viruses inhabiting the skin. Indeed, recent advances have featured the interactions, within the wound environment, between different microbial species and between microbial species and the host immune system. This article reviews the relationship between the skin microbiome and the wound healing process. Although cutaneous wounds are a potential entry site for infection, the wound microbiome can have either a detrimental or a beneficial role on wound healing. Thus, targeting the skin microbiome could represent an essential part of wound healing management.

Wound Healing Goes Viral

During cutaneous wounding, many different cell types are mobilized to reinstate homeostasis, including immune cells, keratinocytes, dermal fibroblasts, and fascia fibroblasts. These responses are essential to stop bleeding, clear microbes, and close the wound to re-establish the skin barrier. Humans, similar to most mammals, are incapable of regenerating fully functional skin after cutaneous wound healing. Instead, scar tissue develops, which is inferior to native skin owing to its lack of skin appendages, unsightly appearance, and compromised mechanical properties (Marshall et al., 2018).

Novel green synthesis of tin nanoparticles by medicinal plant: Chemical characterization and determination of cytotoxicity, cutaneous wound healing and antioxidant properties

In the present study, tin nanoparticles were green-synthesized using the aqueous extract of Foeniculum vulgare leaf aqueous extract. The synthesized SnNPs (tin nanoparticles) were characterized by analytical techniques including EDX (energy dispersive X-ray), FE-SEM (field emission scanning electron microscopy), XRD (X-ray diffraction), UV–vis and FT-IR (Fourier transform-infrared). The cytotoxicity activity of SnNPs was evaluated using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. The nanoparticles were formed in a spherical shape in the range size of 26.45–38.53 nm. In the antioxidant test, the IC50 of F. vulgare, [email protected] (Sn [email protected] F. vulgare) and BHT (butylated hydroxytoluene) against DPPH (2,2-diphenyl-1-picrylhydrazyl) free radicals were 384, 119 and 71 µg/mL, respectively. In the cellular and molecular part of the recent study, the treated cells with [email protected] were assessed by MTT assay for 48h about the cytotoxicity property on normal HUVEC (human umbilical vein endothelial cells) cell line. In vivo experiment, [email protected] ointment significantly decreased (p ≤ 0.01) the wound area, total cells, neutrophil and lymphocyte and notably increased (p ≤ 0.01) the wound contracture, vessel, hydroxyl proline, hexosamine, hexuronic acid and fibrocyte compared to other groups in rats. Further clinical trials are necessary for confirmation of these remedial properties of [email protected] in humans.

Bioprinting a skin patch with dual-crosslinked gelatin (GelMA) and silk fibroin (SilMA): An approach to accelerating cutaneous wound healing.

Clinical settings often face significant obstacles in treating large acute wounds. The alternative of therapeutic approach is needed urgently. Hydrogels derived from natural or synthetic materials may be designed to perform a variety of functions for promoting wound healing. Herein, a 3D bioprinted hydrogel patch is designed for accelerating acute wound healing, which is fabricated with methacryloyl-substituted gelatin (GelMA) and silk fibroin (SilMA) dual-cross-linked by ultraviolet (UV) light. The GelMA with added silk fibroin (GelSilMA) shows improved biodegradation and mechanical properties. Furthermore, SilMA hydrogel can maintain a moisturized healing environment in wound area persistently with adequate degradation capacity. In vivo, GelSilMA (G-S) hydrogel can help to speed wound closure by the improved microenvironment for epidermal tissue regeneration and endogenous collagen generation accordingly. In summary, the G-S hydrogel patch can accelerate acute wound healing efficiently in a relatively simple and inexpensive manner.

Role of enkephalin derivative in promoting wound healing and scar remodeling via increased epidermal growth factor in a mouse model

Background Enkephalin, an endogenous neuropeptide, binds to the delta (δ) opioid receptor and exerts an antinociceptive effect. Recent studies have suggested that neuropeptides might effectuate cutaneous wound healing. Therefore, we investigated the effects of an enkephalin derivative on wound healing and scar formation in vivo.Methods Enkephalin derivatives (leucine-enkephalin) were synthesized using the alanine scan method, and the most promising derivative (E10) was selected for further testing. In 15 C57BL/6N mice, two full-thickness skin defects (10 mm in diameter) were made on both sides of the back (left side, enkephalin group; right side, control group). The enkephalin group was administered 100 μL of E10 (AGGFL, 200 μg/mL), and the control group received phosphate-buffered saline. The wound size was digitally analyzed on days 2, 4, 7, and 10. After 21 days, the scar tissues were histologically evaluated for the scar depression index (SDI), and the epidermal growth factor (EGF) concentration was assessed using an enzyme-linked immunosorbent assay.Results The skin defect percentages were 98.4%±17.9% (day 2), 83.2%±24.0% (day 4), 39.7%±17.4% (day 7), and 16.2%±10.0% (day 10) in the control group and 86.1%±15.0% (day 2), 61.4%±11.6% (day 4), 26.6%±8.8% (day 7), and 16.4%±8.8% (day 10) in the enkephalin group. The SDI values were significantly lower in the enkephalin group (0.06±0.19) than in the control group (0.22±0.13, P&lt;0.001). The EGF level was significantly higher in the enkephalin group (102.2±22.6 pg/mL) than in the control group (42.1±20.5 pg/mL, P&lt;0.001).Conclusions An enkephalin derivative promoted wound healing and reduced depressed scar formation in a mouse model.

Characterization of Dual-Layer Hybrid Biomatrix for Future Use in Cutaneous Wound Healing.

A skin wound without immediate treatment could delay wound healing and may lead to death after severe infection (sepsis). Any interruption or inappropriate normal wound healing, mainly in these wounds, commonly resulted in prolonged and excessive skin contraction. Contraction is a common mechanism in wound healing phases and contributes 40-80% of the original wound size post-healing. Even though it is essential to accelerate wound healing, it also simultaneously limits movement, mainly in the joint area. In the worst-case scenario, prolonged contraction could lead to disfigurement and loss of tissue function. This study aimed to fabricate and characterise the elastin-fortified gelatin/polyvinyl alcohol (PVA) film layered on top of a collagen sponge as a bilayer hybrid biomatrix. Briefly, the combination of halal-based gelatin (4% (w/v)) and PVA ((4% (w/v)) was used to fabricate composite film, followed by the integration of poultry elastin (0.25 mg/mL) and 0.1% (w/v) genipin crosslinking. Furthermore, further analysis was conducted on the composite bilayer biomatrix's physicochemical and mechanical strength. The bilayer biomatrix demonstrated a slow biodegradation rate (0.374967 ± 0.031 mg/h), adequate water absorption (1078.734 ± 42.33%), reasonable water vapour transmission rate (WVTR) (724.6467 ± 70.69 g/m2 h) and porous (102.5944 ± 28.21%). The bilayer biomatrix also exhibited an excellent crosslinking degree and was mechanically robust. Besides, the elastin releasing study presented an acceptable rate post-integration with hybrid biomatrix. Therefore, the ready-to-use bilayer biomatrix will benefit therapeutic effects as an alternative treatment for future diabetic skin wound management.

Evaluation of Cutaneous Wound Healing Activity of Citrus aurantium Fruit Peel Extract-based Ointment in Albino Rats

The current study was aimed to evaluate the wound healing activity of ethyl acetate extract of fruit peels of Citrus aurantium. An ethyl acetate extract of fruit peel of Citrus aurantium was loaded into an ointment base with three different concentrations (0.25% w/w, 0.5% w/w and 1%w/w) and tested for wound healing activity using excision wound model by measuring the healing area and dermal toxicity. Wound healing activity and histopathology studies confirmed that all the tested three concentrations of extract accelerate the wound healing process by decreasing the surface area of the wound and increases the muscle tensile strength. Out of tested ointments, 5% w/w concentration showed comparative activity with the standard. Hence, natural Citrus aurantium peel-based ointment is an alternative ointment in wound healing.