Cutaneous Wound Healing Research Articles

Injectable hydrogel made from antler mesenchyme matrix for regenerative wound healing via creating a fetal-like niche.

Scar formation and loss of cutaneous appendages are the greatest challenges in cutaneous wound healing. Previous studies have indicated that antler reserve mesenchyme (RM) cells and their conditioned medium improved regenerative wound healing with partial recovery of cutaneous appendages. To develop hydrogels from the antler RM matrix (HARM) and evaluate the effect on wound healing. We prepared the hydrogels from the HARM via enzymatic solubilization with pepsin. Then we investigated the therapeutic effects of HARM on a full-thickness cutaneous wound healing rat model using both local injections surrounding the wound and topical wound application. The results showed that HARM accelerated wound healing rate and reduced scar formation. Also, HARM stimulated the regeneration of cutaneous appendages and blood vessels, and reduced collagen fiber aggregation. Further study showed that these functions might be achieved via creating a fetal-like niche at the wound site. The levels of fetal wound healing-related genes, including Collagen III and TGFβ3 treated with HARM were all increased, while the expression levels of Collagen I, TGFβ1, and Engrailed 1 were decreased in the healing. Moreover, the number of stem cells was increased in the fetal-like niche created by HARM, which may contribute to the regeneration of cutaneous appendages. Overall, we successfully developed an injectable hydrogel made from antler RM matrix for the regenerative repair of full-thickness cutaneous wounds. We uncovered the molecular mechanism of the hydrogels in promoting regenerative wound healing, and thus pave the way for HARM to be developed for the clinic use.

Fabrication of a three-dimensional printed gelatin/sodium alginate/nano-attapulgite composite polymer scaffold loaded with leonurine hydrochloride and its effects on osteogenesis and vascularization

Bone tissue engineering scaffolds have made significant progress in treating bone defects in recent decades. However, the lack of a vascular network within the scaffold limits bone formation after implantation in vivo. Recent research suggests that leonurine hydrochloride (LH) can promote healing in full-thickness cutaneous wounds by increasing vessel formation and collagen deposition. Gelatin and Sodium Alginate are both polymers. ATP is a magnesium silicate chain mineral. In this study, a Gelatin/Sodium Alginate/Nano-Attapulgite composite hydrogel was used as the base material first, and the Gelatin/Sodium Alginate/Nano-Attapulgite composite polymer scaffold loaded with LH was then created using 3D printing technology. Finally, LH was grafted onto the base material by an amide reaction to construct a scaffold loaded with LH to achieve long-term LH release. When compared to pure polymer scaffolds, in vitro results showed that LH-loaded scaffolds promoted the differentiation of BMSCs into osteoblasts, as evidenced by increased expression of osteogenic key genes. The results of in vivo tissue staining revealed that the drug-loaded scaffold promoted both angiogenesis and bone formation. Collectively, these findings suggest that LH-loaded Gelatin/Sodium Alginate/Nano-Attapulgite composite hydrogel scaffolds are a potential therapeutic strategy and can assist bone regeneration.

Hydrolytic hydrogels tune mesenchymal stem cell persistence and immunomodulation for enhanced diabetic cutaneous wound healing

Diabetes is associated with an altered global inflammatory state with impaired wound healing. Mesenchymal stem/stromal cells (MSC) are being explored for treatment of diabetic cutaneous wounds due to their regenerative properties. These cells are commonly delivered by injection, but the need to prolong the retention of MSC at sites of injury has spurred the development of biomaterial-based MSC delivery vehicles. However, controlling biomaterial degradation rates in vivo remains a therapeutic-limiting challenge. Here, we utilize hydrolytically degradable ester linkages to engineer synthetic hydrogels with tunable in vivo degradation kinetics for temporally controlled delivery of MSC. In vivo hydrogel degradation rate can be controlled by altering the ratio of ester to amide linkages in the hydrogel macromers. These hydrolytic hydrogels degrade at rates that enable unencumbered cutaneous wound healing, while enhancing the local persistence MSC compared to widely used protease-degradable hydrogels. Furthermore, hydrogel-based delivery of MSC modulates local immune responses and enhances cutaneous wound repair in diabetic mice. This study introduces a simple strategy for engineering tunable degradation modalities into synthetic biomaterials, overcoming a key barrier to their use as cell delivery vehicles.

KY19382 Accelerates Cutaneous Wound Healing via Activation of the Wnt/β-Catenin Signaling Pathway.

The Wnt/β-catenin signaling pathway plays important roles in the multi-phases of wound healing: homeostasis, inflammation, proliferative, and remodeling phases. However, there are no clinically available therapeutic agents targeting the Wnt/β-catenin pathway. In this study, we tested the effect of 5, 6-dichloroindirubin-3'-methoxime (KY19382), a small molecule that activates the Wnt/β-catenin pathway via interference with the function of the negative feedback regulator CXXC5, on cutaneous wound healing. KY19382 significantly enhanced cell migration of human keratinocytes and dermal fibroblasts with increased levels of β-catenin, phalloidin, Keratin 14, proliferating cell nuclear antigen (PCNA), Collagen I, and alpha-smooth muscle actin (α-SMA) by activating the Wnt/β-catenin signaling pathway without causing significant cytotoxicity. In addition, levels of Collagen I, Keratin 14, PCNA, and stem cell markers were significantly increased by KY19382 in a cutaneous murine wound healing model. Moreover, KY19382 treatment accelerated re-epithelialization and neo-epidermis formation with collagen deposition and stem cell activation at an early stage of cutaneous wound healing. Overall, KY19382 accelerates wound healing via activating the Wnt/β-catenin pathway, and may have the potential to be used for the development of a new wound healing agent.

Stem Cells and Exosome Applications for Cutaneous Wound Healing: From Ground to Microgravity Environment.

The increasing number of astronauts entering microgravity environments for long-term space missions has resulted in serious health problems, including accidental injury and trauma. Skin, as the largest organ and outermost layer of the human body, has the ability to self-renew and withstand a variety of harmful biological and environmental influences. Recent spaceflight experiments and simulated studies have begun to concern the effects of microgravity on the growth of skin cells and the process of cutaneous wound healing. However, the mechanisms of the adverse effects of microgravity on skin cells and potential intervention measures are still limited. Stem cells and their exosomes provide unique opportunities for the cutaneous wound healing as they have been used to improve skin repair. This review discusses the effects of microgravity on wound healing, from cell morphological changes to molecular level alterations. Furthermore, the current research on wound healing treatment utilizing stem cells and their exosomes on the ground is summarized. Finally, this review proposes promising therapeutic strategies using stem cells or exosomes for wound healing in the microgravity environment. Graphical Abstract.

Forkhead box A1 induces angiogenesis through activation of the S100A8/p38 MAPK axis in cutaneous wound healing

BackgroundThe association between S100 calcium-binding protein A8 (S100A8) and angiogenesis has been reported in previous reports. This study focuses on the roles of S100A8 in the angiogenesis of human dermal microvascular endothelial cells (HDMECs) and in cutaneous wound healing in mice.MethodsCandidate genes related to angiogenesis activity were screened using a GSE83582 dataset. The overexpression DNA plasmid of S100A8 was transfected into HDMECs to analyze its effect on cell proliferation, migration, and angiogenesis. Full-thickness skin wounds were induced on mice, followed by adenovirus treatments to analyze the function of gene alteration in wound healing and pathological changes. The upstream regulator of S100A8 was predicted by bioinformatics analysis and verified by luciferase and immunoprecipitation assays. The role of the forkhead box A1 (FOXA1)-S100A8 interaction in p38 MAPK activation and angiogenesis were validated by rescue experiments.ResultsS100A8 was identified as a gene significantly correlated with angiogenesis. The S100A8 upregulation promoted the proliferation, migration, and angiogenesis of HDMECs, and it promoted p38 MAPK phosphorylation. Treatment of SB203580, a p38 MAPK inhibitor, blocked the promoting effect of S100A8. FOXA1 was identified as an upstream factor of S100A8 promoting its transcription. FOXA1 overexpression in HDMECs increased p38 MAPK phosphorylation and enhanced the activity of cells, which were blocked by the S100A8 inhibition. Similar results were reproduced in vivo where FOXA1 overexpression accelerated whereas the S100A8 knockdown retarded the cutaneous wound healing in mice.ConclusionFOXA1 mediates the phosphorylation of p38 MAPK through transcription activation of S100A8, thereby inducing angiogenesis and promoting cutaneous wound healing.

Cascade enzymatic preparation of carboxymethyl chitosan-based multifunctional hydrogels for promoting cutaneous wound healing

Designing wound dressings with inherent multifunctional therapeutic effects is desirable for clinical applications. Herein, a series of multifunctional carboxymethyl chitosan (CMCS)-based hydrogels were fabricated by the facile urate oxidase (UOX)-horseradish peroxidase (HRP) cascade enzymatic crosslinking system. For the first time, the cascade enzymatic crosslinking system was not only used for preparing hydrogel wound dressings but also for accelerating wound healing due to the activity retention of the self-compartmental enzymes. A CMCS derivative (HCMCS-mF) synthesized by successively grafting 4-hydroxybenzaldehyde (H) and 5-methylfurfural (mF) on CMCS and a quaternary ammonium crosslinker (QMal) with terminal grafting maleimide (Mal) groups were combined with enzymatic system for the facile preparation of hydrogels. The mild Diels-Alder (DA) crosslinking reaction between mF and Mal groups constructed the first network of hydrogels. The cascade UOX-HRP system mediated the oxidative crosslinking of phenols thus forming the second gel network. Self-entrapped UOX maintained its enzymatic activity and could continuously catalyze the oxidation of uric acid, generating therapeutic allantoin. These porous, degradable, mechanically stable hydrogels with excellent antioxidant performance and enhanced antibacterial capacity could effectively accelerate skin wound repair by simultaneously reducing oxidative stress, relieving inflammation, promoting collagen deposition and upregulating the expression level of CD31.

Effects of TP63 mutations on keratinocyte adhesion and migration.

The goal of this study was to investigate the molecular mechanisms responsible for the formation of skin erosions in patients affected by Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC). This ectodermal dysplasia is caused by mutations in the TP63 gene, which encodes several transcription factors that control epidermal development and homeostasis. We generated induced pluripotent stem cells (iPSC) from AEC patients and corrected the TP63 mutations using genome editing tools. Three pairs of the resulting conisogenic iPSC lines were differentiated into keratinocytes (iPSC-K). We identified a significant downregulation of key components of hemidesmosomes and focal adhesions in AEC iPSC-K compared to their gene-corrected counterparts. Further, we demonstrated reduced AEC iPSC-K migration, suggesting the possibility that a process critical for cutaneous wound healing might be impaired in AEC patients. Next, we generated chimeric mice expressing a TP63-AEC transgene and confirmed a downregulation of these genes in transgene-expressing cells in vivo. Finally, we also observed these abnormalities in AEC patient skin. Our findings suggest that integrin defects in AEC patients might weaken the adhesion of keratinocytes to the basement membrane. We propose that reduced expression of extracellular matrix adhesion receptors, potentially in conjunction with previously identified desmosomal protein defects, contribute to skin erosions in AEC.

In Situ Precision Cell Electrospinning as An Efficient Stem Cell Delivery Approach for Cutaneous Wound Healing.

Mesenchymal stem cell (MSC) therapies have been brought forward as a promising treatment modality for cutaneous wound healing. However, current approaches for stem cell delivery have many drawbacks, such as lack of targetability and cell loss, leading to poor efficacy of stem cell therapy. To overcome these problems, in the present study, wedeveloped an in situ cell electrospinning system as an attractive approach for stem cell delivery. MSCs have a high cell viability over 90% even with a high applied voltage of 15kV post-cell electrospinning process. In addition, cell electrospinning does not show any negative effect on surface marker expression and differentiation capacity of MSCs. In vivo studies demonstrated that in situ cell electrospinning treatment could promote cutaneous wound healing through direct deposition of bioactive fish gelatin fibers and MSCs onto wound sites, leading to a synergic therapeutic effect. Ourapproach enhanced extracellular matrix remodeling by increasing collagen deposition, promoted angiogenesis by increasing the expression of VEGF and forming small blood vessels, and dramatically reduced the expression of IL-6 during the wound healing. The use of in situ cell electrospinning system potentially provides a rapid, no touch, personalized treatment for cutaneous wound healing. This article is protected by copyright. All rights reserved.

Effects of Bacteriocin Extracted from Lactobacillus rhamnosus on Cutaneous Wound Healing in Mice

Aim: This study evaluates the effects of bacteriocin produced by Lactobacillus rhamnosus on cutaneous wound healing in mice.
 Study Design: Randomized experimental design was employed in the study.
 Methodology: Probiotic L. rhamnosus was isolated from nono milk using MRS agar media and identified based on morphological and biochemical characteristics. The potent bacterium was subjected to bacteriocin production. Antimicrobial activity of the bacteriocin was carried out against wound pathogenic bacteria and wound healing effects of the bacteriocins were assessed on mice. 2 mm cutaneous wound was induced on the mice and crude bacteriocin was topically applied on the wounds. White blood cell count was carried out after days 3, 5, 9, and 14. Histopathological analyses were performed after day 14.
 Results: Crude bacteriocin was effective against wound pathogenic bacteria such as S. aureus, P. aeruginosa and E. coli. Topical application of bacteriocin showed a faster and better wound healing when compared to positive control groups in P. aeruginosa infected wound model. Histology examination revealed an increase wound healing time in L. rhamnosus bacteriocin treated mice. The crude bacteriocins demonstrated excellent wound-healing activity in skin excision albino mice model.
 Conclusion: L. rhamnosus bacteriocin had various beneficial actions on wounds. It improved wound healing, inhibited wound pathogens and increase wound healing time.

A wearable OLED medical device for enhanced cutaneous wound healing and patient comfort: revolutionizing dermatology

Integrating organic light-emitting diodes (OLEDs) with light therapy can significantly advance biomedical applications by offering non-invasive, precise, and customizable treatments. Developing innovative device designs and performing cellular tests is essential to assess the safety and effect of OLED-based light therapies in dermatology. As such, a wearable OLED medical device prototype has been created for easy attachment to the body, ensuring consistent exposure to skin injuries due to its comfortable fit and user-friendly operation. Moreover, it has demonstrated effectiveness in enhancing wound healing, as indicated by a max 23% increase in fibroblast proliferation at the cellular level.

Angiopoietin-like 4 promotes epidermal stem cell proliferation and migration and contributes to cutaneous wound re-epithelialization.

Proliferation and migration of epidermal stem cells (EpSCs) are essential for epithelialization during skin wound healing. Angiopoietin-like 4 (ANGPTL4) has been reported to play an important role in wound healing, but the mechanisms involved are not fully understood. Here, we investigate the contribution of ANGPTL4 to full-thickness wound re-epithelialization and the underlying mechanisms using Angptl4-knockout mice. Immunohistochemical staining reveals that ANGPTL4 is significantly upregulated in the basal layer cells of the epidermis around the wound during cutaneous wound healing. ANGPTL4 deficiency impairs wound healing. H&E staining shows that ANGPTL4 deficiency significantly reduces the thickness, length and area of the regenerated epidermis postwounding. Immunohistochemical staining for markers of EpSCs (α6 integrin and β1 integrin) and cell proliferation (PCNA) shows that the number and proliferation of EpSCs in the basal layer of the epidermis are reduced in ANGPTL4-deficient mice. In vitro studies show that ANGPTL4 deficiency impedes EpSC proliferation, causes cell cycle arrest at the G1 phase and reduces the expressions of cyclins D1 and A2, which can be reversed by ANGPTL4 overexpression. ANGPTL4 deletion suppresses EpSC migration, which is also rescued by ANGPTL4 overexpression. Overexpression of ANGPTL4 in EpSCs accelerates cell proliferation and migration. Collectively, our results indicate that ANGPTL4 promotes EpSC proliferation by upregulating cyclins D1 and A2 expressions and accelerating the cell cycle transition from G1 to S phase and that ANGPTL4 promotes skin wound re-epithelialization by stimulating EpSC proliferation and migration. Our study reveals a novel mechanism underlying EpSC activation and re-epithelialization during cutaneous wound healing.

Shockwave versus ultrasound therapy in the enhancement of Aloe vera in cutaneous wound healing

Objective: To investigate the healing efficacy of topical Aloe vera enhanced by shockwave or ultrasound therapy on wounds in rats and compare both effects. Method: A total of 75 male albino rats were randomly divided into equal groups A, B, C, D and E. Under anaesthesia, a wound (6cm2) was created on the back of each rat. Group A received topical Aloe vera under occlusive dressing followed by shockwave therapy with the following parameters: 600 shocks, four pulses/second and 0.11mJ/mm2. Group B received topical Aloe vera under occlusive dressing followed by therapeutic ultrasound with the following parameters: pulsed mode, 2:8 duty cycle, 1MHz and 0.5 W/cm2. Group C received the same treatment as group A but in a reversed sequence—the shockwave therapy followed by the Aloe vera gel. Group D received the same treatment as group B but in a reversed sequence—therapeutic ultrasound followed by the Aloe vera gel. And control group E only received topical Aloe vera under occlusive dressing. Each group received three sessions per week, for two weeks. Wound extent and shrinkage rates were measured at study initiation and at the end of each week. Results: There were significant wound reductions in groups A and B compared to C and D, respectively, and in group A compared to group B. Conclusion: Shockwaves and ultrasound were found to amplify the effect of the Aloe vera on the wound, and there was improved wound healing in the shockwave group A compared to the ultrasound group B.

Preliminary Study on Human Adipose Stem Cells Promoting Skin Wound Healing through Notch Signaling Pathway.

Mesenchymal stem cells (MSCs) have been documented as possible candidates for wound healing treatment because their use could reinforce the regenerative capacity of many tissues. Human adipose stem cells (hADSCs) have the advantages of easy access, large quantity and easy operation. They can be fully applied in the treatment of skin wounds. In this study, we aim to explore the roles and potential mechanisms of hADSCs in cutaneous wound healing. hADSCs were obtained from human subcutaneous fat. Adipocytes and osteocytes differentiated from hADSCs were determined by staining with Oil Red O and alkaline phosphatase (ALP), respectively. We assessed the effects of hADSCs and hADSC conditional medium (CM) on wound healing in an injury model of mice. Then, we investigated the biological effects of hADSCs on human keratinocytes HaCAT cells in vitro. The results showed that hADSCs could be successfully differentiated into osteogenic and lipogenic cells. hADSCs and hADSCs-CM significantly promote skin wound healing in vivo. hADSCs significantly promoted HaCAT cell proliferation and migration by activating the Notch signaling pathway and activated the AKT signaling pathway by Rps6kb1 kinase in HaCAT cells. In addition, we found that hADSCs-mediated activation of Rps6kb1/AKT signaling was dependent on the Notch signaling pathway. We demonstrated that hADSCs can promote skin cell-HaCAT cell proliferation and migration via the Notch pathway, suggesting that hADSCs may provide an alternative therapeutic approach for the treatment of skin injury.

NIR responsive composite nanomaterials with in-situ deposition of cascaded nanozymes for multiple synergistic therapy of bacterial infection in diabetic mice

The bacterial infection of chronic wounds caused by diabetes has imposed a significant burden on society and families. Therefore, the collaborative and emerging antibacterial strategies are urgently designed and invented to reduce the burden of bacteria on wounds. Herein, an aptamer functionalized and near-infrared light responsive nano-antibacterial material (CuS@Pt-Au/Apt NPs) based on cascaded nanozymes is successfully constructed for the synergistic therapy of wound infection in diabetic mice. In vitro performance assays verify that CuS@Pt-Au/Apt NPs exhibit the sustained release of hydroxyl radical (·OH) and excellent photothermal properties. Varies in vitro antibacterial experiments demonstrate that the minimum inhibitory concentrations (MICs) of CuS@Pt-Au/Apt against Escherichia coli (E.coli) and Staphylococcus aureus (S.aureus) are both 128 μg·mL−1 under NIR irradiation and glucose catalysis, while validate the efficient in vitro bactericidal activity, significant glutathione consumption and its antibacterial mechanism. In vivo anti-infection assays prove that CuS@Pt-Au/Apt NPs perform the best cutaneous wound healing capability with a remaining infected area of <2% for bacterial infection of diabetes, and significantly reduce the occurrence of inflammation at the infected wounds. This antibacterial strategy integrating targeting, chemodynamic therapy (CDT) and photothermal therapy (PTT) not only achieves synergistic and enhanced antimicrobial effects, but also addresses the limitations of nanozymes and promotes their biomedical applications.

Ethyl gallate isolated from phenol-enriched fraction of Caesalpinia mimosoides Lam. Promotes cutaneous wound healing: a scientific validation through bioassay-guided fractionation.

The tender shoots of Caesalpinia mimosoides Lam. are used ethnomedically by the traditional healers of Uttara Kannada district, Karnataka (India) for the treatment of wounds. The current study was aimed at exploring phenol-enriched fraction (PEF) of crude ethanol extract of tender shoots to isolate and characterize the most active bio-constituent through bioassay-guided fractionation procedure. The successive fractionation and sub-fractionation of PEF, followed by in vitro scratch wound, antimicrobial, and antioxidant activities, yielded a highly active natural antioxidant compound ethyl gallate (EG). In vitro wound healing potentiality of EG was evidenced by a significantly higher percentage of cell migration in L929 fibroblast cells (97.98 ± 0.46% at 3.81μg/ml concentration) compared to a positive control group (98.44 ± 0.36%) at the 48th hour of incubation. A significantly higher rate of wound contraction (98.72 ± 0.41%), an elevated tensile strength of the incised wound (1,154.60 ± 1.42g/mm2), and increased quantity of connective tissue elements were observed in the granulation tissues of the 1% EG ointment treated animal group on the 15th post-wounding day. The accelerated wound healing activity of 1% EG was also exhibited by histopathological examinations through Hematoxylin and Eosin, Masson's trichome, and Toluidine blue-stained sections. Significant up-regulation of enzymatic and non-enzymatic antioxidant contents (reduced glutathione, superoxide dismutase, and catalase) and down-regulation of oxidative stress marker (lipid peroxidation) clearly indicates the effective granular antioxidant activity of 1% EG in preventing oxidative damage to the skin tissues. Further, in vitro antimicrobial and antioxidant activities of EG supports the positive correlation with its enhanced wound-healing activity. Moreover, molecular docking and dynamics for 100ns revealed the stable binding of EG with cyclooxygenase-2 (-6.2kcal/mol) and matrix metalloproteinase-9 (-4.6kcal/mol) and unstable binding with tumor necrosis factor-α (-7.2kcal/mol), suggesting the potential applicability of EG in inflammation and wound treatment.

An Engineered Dermal Substitute with Mesenchymal Stem Cells Enhances Cutaneous Wound Healing.

The treatment of refractory cutaneous wounds remains to be a clinical challenge. There is growing evidence to show that mesenchymal stem cells (MSCs) have great potential in promoting wound healing. However, the therapeutic effects of MSCs are greatly dampened by their poor survival and engraftment in the wounds. To address this limitation, in this study, MSCs were grown into a collagen-glycosaminoglycan (C-GAG) matrix to form a dermis-like tissue sheet, named engineered dermal substitute (EDS). When seeded on C-GAG matrix, MSCs adhered rapidly, migrated into the pores, and proliferated readily. When applied onto excisional wounds in healthy and diabetic mice, the EDS survived well, and accelerated wound closure, compared with C-GAG matrix alone or MSCs in collagen hydrogel. Histological analysis revealed that EDS prolonged the retention of MSCs in the wounds, associated with increased macrophage infiltration and enhanced angiogenesis. RNA-Seq analysis of EDS-treated wounds uncovered the expression of abundant human chemokines and proangiogenic factors and their corresponding murine receptors, suggesting a mechanism of ligand/receptor-mediated signals in wound healing. Thus, our results indicate that EDS prolongs the survival and retention of MSCs in the wounds and enhances wound healing.

Divergent functions of histone acetyltransferases KAT2A and KAT2B in keratinocyte self-renewal and differentiation.

The mammalian epidermis undergoes constant renewal, replenished by a pool of stem cells and terminal differentiation of their progeny. This is accompanied by changes in gene expression and morphology that are orchestrated, in part, by epigenetic modifiers. Here, we define the role of the histone acetyltransferase KAT2A in epidermal homeostasis and provide a comparative analysis that reveals key functional divergence with its paralog KAT2B. In contrast to the reported function of KAT2B in epidermal differentiation, KAT2A supports the undifferentiated state in keratinocytes. RNA-seq analysis of KAT2A- and KAT2B- depleted keratinocytes revealed dysregulated epidermal differentiation. Depletion of KAT2A led to premature expression of epidermal differentiation genes in the absence of inductive signals, whereas loss of KAT2B delayed differentiation. KAT2A acetyltransferase activity was indispensable in regulating epidermal differentiation gene expression. The metazoan-specific N terminus of KAT2A was also required to support its function in keratinocytes. We further showed that the interplay between KAT2A- and KAT2B-mediated regulation was important for normal cutaneous wound healing in vivo. Overall, these findings reveal a distinct mechanism in which keratinocytes use a pair of highly homologous histone acetyltransferases to support divergent functions in self-renewal and differentiation processes.

Preparation and evaluation of a polycaprolactone/chitosan/propolis fibrous nanocomposite scaffold as a tissue engineering skin substitute.

Recently, the application of nanofibrous mats for dressing skin wounds has received great attention. In this study, we aimed to fabricate and characterize an electrospun nanofibrous mat containing polycaprolactone (PCL), chitosan (CTS), and propolis for use as a tissue-engineered skin substitute. Raw propolis was extracted, and its phenolic and flavonoid contents were measured. The physiochemical and biological properties of the fabricated mats, including PCL, PCL/CTS, and PCL/CTS/Propolis were evaluated by scanning electron microscopy (SEM), atomic force microscopy (AFM), mechanical analysis, swelling and degradation behaviors, contact angle measurement, cell attachment, DAPI staining, and MTT assay. On the other hand, the drug release pattern of propolis from the PCL/CTS/Propolis scaffold was determined. A deep second-degree burn wound model was induced in rats to investigate wound healing using macroscopical and histopathological evaluations. The results revealed that the propolis extract contained high amounts of phenolic and flavonoid compounds. The fabricated scaffold had suitable physicochemical and mechanical properties. Uniform, bead-free, and well-branched fibers were observed in SEM images of mats. AFM analysis indicated that the addition of CTS and propolis to PCL elevated the surface roughness. MTT results revealed that the electrospun PCL/CTS/Propolis mat was biocompatible. The presence of fibroblast cells on the PCL/CTS/Propolis mats was confirmed by DAPI staining and SEM images. Also, propolis was sustainably released from the PCL/CTS/Propolis mat. The animal study revealed that addition of propolis significantly improved wound healing. The nanofibrous PCL/CTS/Propolis mat can be applied as a tissue-engineered skin substitute for healing cutaneous wounds, such as burn wounds.

Electrochemical Devices in Cutaneous Wound Healing.

In healthy skin, vectorial ion transport gives rise to a transepithelial potential which directly impacts many physiological aspects of skin function. A wound is a physical defect that breaches the epithelial barrier and changes the electrochemical environment of skin. Electroceutical dressings are devices that manipulate the electrochemical environment, host as well as microbial, of a wound. In this review, electroceuticals are organized into three mechanistic classes: ionic, wireless, and battery powered. All three classes of electroceutical dressing show encouraging effects on infection management and wound healing with evidence of favorable impact on keratinocyte migration and disruption of wound biofilm infection. This foundation sets the stage for further mechanistic as well as interventional studies. Successful conduct of such studies will determine the best dosage, timing, and class of stimulus necessary to maximize therapeutic efficacy.