Cutaneous Wound Healing Research Articles

Restoring sweat gland function in mice using regenerative sweat gland cells derived from chemically reprogrammed human epidermal keratinocytes

The regeneration of sweat glands (SwGs) plays a pivotal role in the functional recovery of extensive skin wounds. Recent research has illuminated the possibility of reprogramming human epidermal keratinocytes (HEKs) into induced SwG cells through the ectopic expression of ectodysplasin A. However, the clinical application of this genetic manipulation approach is inherently limited. In this study, we present findings demonstrating that a combination of six compounds can effectively and speedily reprogram HEKs in culture into fully functional SwG cells. These chemically induced SwG-like cells (ciSGCs) closely resemble the morphology, phenotypes, and functional properties of human primary SwG ductal cells. Furthermore, ciSGCs can be stimulated to differentiate into mature SwG cell types in vitro. In a 3D culture system, they can also generate SwG organoids that exhibit structural and biological features akin to native SwGs. Upon transplantation into scalded mouse paw skin, ciSGCs significantly expedited cutaneous wound healing and completely restored the structural and functional aspects of the SwGs. In conclusion, the small molecule cocktail-directed SwG reprogramming offers a non-transgenic and controllable strategy for producing high-quality, clinical-grade SwG cells, showing immense potential for the treatment of burn patients.

Current Trends on Innovative Technologies in Topical Wound Care for Advanced Healing and Management.

To investigate critically traditional and modern techniques for cutaneous wound healing and to provide comprehensive information on these novel techniques to encounter the challenges with the existing wound healing methods. The financial burden and mortality associated with wounds is increasing, so managing wounds is essential. Traditional wound treatments include surgical and non-surgical methods, while modern techniques are advancing rapidly. This review examines the various traditional and modern techniques used for cutaneous wound healing. Traditional wound treatments include surgical techniques such as debridement, skin flaps, and grafts. Non-surgical treatments include skin replacements, topical formulations, scaffold-based skin grafts, and hydrogel-based skin dressings. More modern techniques include using nanoparticles, growth factors, and bioactive substances in wound dressings. Bioengineered skin substitutes using biomaterials, cells, and growth factors are also being developed. Other techniques include stem cell therapy, growth factor/cytokine therapy, vacuum-assisted wound closure, and 3D-printed/bio-printed wound dressings. Traditional wound treatments have been replaced by modern techniques such as stem cell therapy, growth factor/cytokine therapy, vacuum-assisted wound closure, and bioengineered skin substitutes. However, most of these strategies lack effectiveness and thorough evaluation. Therefore, further research is required to develop new techniques for cutaneous wound healing that are effective, cost-efficient, and appealing to patients.

Reprogramming of epidermal keratinocytes by PITX1 transforms the cutaneous cellular landscape and promotes wound healing.

Cutaneous wound healing is a slow process that often terminates with permanent scarring while oral wounds, in contrast, regenerate damage faster. Unique molecular networks in epidermal and oral epithelial keratinocytes contribute to the tissue-specific response to wounding, but key factors that establish those networks and how the keratinocytes interact with their cellular environment remain to be elucidated. The transcription factor PITX1 is highly expressed in the oral epithelium but is undetectable in cutaneous keratinocytes. To delineate if PITX1 contributes to oral keratinocyte identity, cell-cell interactions, and the improved wound healing capabilities, we ectopically expressed PITX1 in the epidermis of murine skin. Using comparative analysis of murine skin and oral (buccal) mucosa with scRNA-seq and spatial transcriptomics, we found that PITX1 expression enhances epidermal keratinocyte migration, proliferation, and alters differentiation to a quasi-oral keratinocyte state. PITX1+ keratinocytes reprogram intercellular communication between skin-resident cells to mirror buccal tissue while also stimulating the influx of neutrophils that establish a pro-inflammatory environment. Furthermore, PITX1+ skin heals significantly faster than control skin via increased keratinocyte activation and migration and a tunable inflammatory environment. These results illustrate that PITX1 programs oral keratinocyte identity and cellular interactions while also revealing critical downstream networks that promote wound closure.

Gene Augmentation Techniques to Stimulate Wound Healing Process: Progress and Prospects.

Gene therapy has traditionally been used to treat individuals with late-stage cancers or congenital abnormalities. Numerous prospects for therapeutic genetic modifications have emerged with the discovery that gene therapy applications are far more extensive, particularly in skin and exterior wounds. Cutaneous wound healing is a complex, multistep process involving multiple steps and mediators that operate in a network of activation and inhibition processes. This setting presents a unique obstacle for gene delivery. Many gene delivery strategies have been developed, including liposomal administration, high-pressure injection, viral transfection, and the application of bare DNA. Among several gene transfer techniques, categorical polymers, nanoparticles, and liposomalbased constructs show great promise for non-viral gene transfer in wounds. Clinical experiments have shown that efficient transportation of certain polypeptides to the intended wound location is a crucial factor in wound healing. Genetically engineered cells can be used to produce and control the delivery of specific growth factors, thereby addressing the drawbacks of mechanically administered recombinant growth factors. We have discussed how repair mechanisms are based on molecules and cells, as well as their breakdown, and provided an overview of the methods and research conducted on gene transmission in tissue regeneration.

Mesenchymal stromal cells-derived small extracellular vesicles protect against UV-induced photoaging via regulating pregnancy zone protein.

Ultraviolet (UV) radiation is the primary extrinsic factor in skin aging, contributing to skin photoaging, actinic keratosis (AK), and even squamous cell carcinoma (SCC). Currently, the beneficial role of mesenchymal stromal cell-derived small extracellular vesicles (MSC-sEVs) in cutaneous wound healing has been widely reported, but the field of photoaging remains to be explored. Our results suggested that human umbilical cord MSC-derived sEVs (hucMSC-sEVs) intervention could effectively alleviate skin photoaging phenotypes in vivo and in vitro, including ameliorating UV-induced histopathological changes in the skin and inhibiting oxidative stress and collagen degradation in dermal fibroblasts (DFs). Mechanistically, pretreatment with hucMSC-sEVs reversed UVA-induced down-regulation of pregnancy zone protein (PZP) in DFs, and achieved photoprotection by inhibiting matrix metalloproteinase-1 (MMP-1) expression and reducing DNA damage. Clinically, a significant decrease in PZP in AK and SCC in situ samples was observed, while a rebound appeared in the invasive SCC samples. Collectively, our findings reveal the effective role of hucMSC-sEVs in regulating PZP to combat photoaging and provide new pre-clinical evidence for the potential development of hucMSC-sEVs as an effective skin photoprotective agent.

Wound Healing, Metabolite Profiling, and In Silico Studies of Aspergillus terreus.

Burn injuries, which significantly affect global public health, require effective treatment strategies tailored to varying severity. Fungi are considered a sustainable, easily propagated source for lead therapeutic discovery. In this study, we explored the burn wound healing potential of Aspergillus terreus through a combination of in vitro, in vivo, metabolite profiling, and in silico analysis. The in vitro scratch assays performed with human skin fibroblast cells showed promising wound healing activity. Furthermore, the burn-induced rats model showed a marked improvement in cutaneous wound healing, evidenced by an accelerated rate of wound closure and better skin regeneration after A. terreus extract treatment at 14 days. The results of this study demonstrated significant enhancements in wound closure and tissue regeneration in the treated rat model, surpassing the outcomes of standard treatments. This controlled healing process, evidenced by superior collagen synthesis and angiogenesis and confirmed by histopathological studies, suggests that A. terreus has potential beyond the traditionally studied fungal metabolites. The metabolite profiling of 27 bioactive compounds was further investigated by docking analysis for the potential inhibition of the NF-κB pathway, which has an important function in inflammation and wound repair. The compounds eurobenzophenone A (7), aspernolide D (16), asperphenalenone A (23), aspergilate D (15), kodaistatin A (18), and versicolactone A (14) showed the highest binding affinity to the target protein with a pose score of -16.86, -14.65, -12.65, -12.45, -12.19, and -12.08 kcal/mol, respectively. Drug-likeness properties were also conducted. The findings suggest the potential wound healing properties of A. terreus as a source for lead therapeutic candidate discovery.

Treatment of Full-Thickness Cutaneous Wounds Using a Novel Fish Skin Acellular Dermal Powder as Hydrogel with Gene Expression of Some Growth Factors Genes

The purpose of this study is to evaluate how well fish skin acellular dermal powder hydrogel (FADPH) promotes the healing of cutaneous wounds in Iraqi bucks. 48 of full-thickness cutaneous wounds (3X3 cm) created on the dorsal back of twelve bucks, each two wounds on both sides. Then, divided into two groups according to treatment method (6 bucks /group). The wounds in control group (A), were left without treatment and the wounds in treatment group (B) were treated by topical application of (FADPH). The outcomes were assessed clinically, morphometrically scoring at (7, 14, 35, and 42) days post treatment, and gene expression by RT-PCR of two genes including fibroblast growth factor (FGF) and epidermal growth factor (EGF) at three times periods (0,7 and 14) days and histopathological assessment at (7,14, 35 and 42) days post treatment. The scoring results of group B showed that the percentages of scoring results were significantly higher than that of control wounds at the level of (P<0.001) from the first 7 days until the end of the study. Also, results of gene expression of FGF and EGF was considerably higher in the treated group than control group at the level of (p<0.001). The histopathological results in group B showed faster re- epithelialization of the epidermis, proliferation of fibrin and regenerated epithelia, dense collagen fibers, and finally complete regeneration of the epidermal layer at the end of study in compared with group A which was showed slowly development in wound healing proses and highly inflammatory reaction. In conclusion, FADM hydrogel enhanced and accelerated the healing of skin wounds in male goats.

GRHL2 regulates keratinocyte EMT-MET dynamics and scar formation during cutaneous wound healing

After cutaneous wounds successfully heal, keratinocytes that underwent the epithelial-mesenchymal transition (EMT) regain their epithelial characteristics, while in scar tissue, epidermal cells persist in a mesenchymal state. However, the regulatory mechanisms governing this reversion are poorly understood, and the impact of persistent mesenchymal-like epidermal cells in scar tissue remains unclear. In the present study, we found that during wound healing, the regulatory factor GRHL2 is highly expressed in normal epidermal cells, downregulated in EMT epidermal cells, and upregulated again during the process of mesenchymal-epithelial transition (MET). We further demonstrated that interfering with GRHL2 expression in epidermal cells can effectively induce the EMT. Conversely, the overexpression of GRHL2 in EMT epidermal cells resulted in partial reversion of the EMT to an epithelial state. To investigate the effects of failed MET in epidermal cells on skin wound healing, we interfered with GRHL2 expression in epidermal cells surrounding the cutaneous wound. The results demonstrated that the persistence of epidermal cells in the mesenchymal state promoted fibrosis in scar tissue, manifested by increased thickness of scar tissue, deposition of collagen and fibronectin, as well as the activation of myofibroblasts. Furthermore, the miR-200s/Zeb1 axis was perturbed in GRHL2 knockdown keratinocytes, and transfection with miR-200s analogs promoted the reversion of EMT in epidermal cells, which indicates that they mediate the EMT process in keratinocytes. These results suggest that restoration of the epithelial state in epidermal cells following the EMT is essential to wound healing, providing potential therapeutic targets for preventing scar formation.

Development of low-molecular-weight polysaccharide-based wound dressings for full-thickness cutaneous wound healing via coacervate formation

The development of polysaccharide-based wound dressings that are easy to prepare, adhere to tissue, adapt to diverse shapes and exhibit tunable mechanical properties holds significant clinical interest. This study introduced a simple spontaneous liquid-liquid phase separation technique employing low-molecular-weight and high polyion concentration of chitosan (CS) and hyaluronic acid (HA) to fabricate CS/HA coacervates. Upon increasing the molecular weight of chitosan from 7 kDa to 250 kDa, a transition in the CS/HA coacervates from liquid-like state to an elastic liquid and eventually to a solid-like state was observed. The resulting CS/HA coacervates demonstrated robust water resistance and adhesion to skin tissue. Notably, the molecular weight of chitosan significantly influenced the mechanical properties and hydration levels of the CS/HA coacervates. Moreover, in vivo studies using a full-thickness cutaneous defect model revealed that the CS/HA coacervates, prepared using 100 kDa chitosan, markedly accelerate wound healing. The coacervates' ease of preparation, wet adhesion, heterogeneous structure, suitability for irregularly shaped wounds, and exceptional wound healing promotion of the coacervates qualify them as an optimal wound dressing.

Inhibition of Ubiquitin C-Terminal Hydrolase L1 Facilitates Cutaneous Wound Healing via Activating TGF-β/Smad Signalling Pathway in Fibroblasts.

Ubiquitin C-terminal hydrolase L1 (UCHL1) plays vital roles in cell proliferation, angiogenesis, inflammation and oxidative stress. Nevertheless, it is unclear whether UCHL1 could regulate the biologic behaviour of cells and ultimately influences wound healing. We aim to illustrate the roles and the underlying mechanism of UCHL1 in cutaneous wound healing. Murine full-thickness excisional wound model was utilised to study the effects of UCHL1 on wound healing through topical administration of the UCHL1 inhibitor LDN57444, followed by assessment of wound areas and histological alterations. Subsequently, ethynyldeoxyuridine, scratch and transwell assays were performed to examine fibroblast migration and proliferation. The extracellular matrix (ECM)-related genes expression and transforming growth factor-β (TGF-β)/Smad signalling pathways activation were investigated by immuno-fluorescent staining, Western blots and quantitative reverse transcription polymerase chain reaction. We identified elevated UCHL1 expression in non-healing wound tissues. The UCHL1 expression displayed a dynamic change and reached a peak on Day-7 post-wounding during the healing process in mice. Cutaneous administration of LDN57444 promoted wound healing by facilitating collagen deposition, myofibroblast activation and angiogenesis. Invitro experiments demonstrated that UCHL1 concentration dependently inhibited migration, ECM synthesis and activation of human dermal fibroblasts, which was mechanistically related to downregulation of TGF-β/Smad signalling. Furthermore, these effects could be reversed by TGF-β inhibitor SB431542. Our findings reveal that UCHL1 is a negative regulator of cutaneous wound healing and considered as a novel prospective therapeutic target for effective wound healing.

Amelioration of full-thickness cutaneous wound healing using stem cell exosome and zinc oxide nanoparticles in rats

BackgroundWound healing is a complex procedure that requires the coordination of several factors, so this study aimed to assess the zinc oxide nanoparticles’ regenerated effect and stem cell exosomes on full-thickness wounds in rats. MethodsSeventy-two Wistar male rats were subjected to a full-thickness skin defect (20 mm2) on the dorsal surface of each rat between two shoulder joints. The rats were randomized into four groups (18/group) according to wound treatments. The wounds were irrigated with normal saline (Control group), or the wound's edges were subcutaneously injected daily with 0.3 ml of exosome (Exo-group), or 1 ml of zinc oxide nanoparticles (ZnO2-NPs group), or 0.3 ml of exosome in combined with 1 ml of zinc oxide nanoparticles (Exo/ZnO2-NPs group). On the 7th, 14th, and 21st days post-wounding, the weight of the rats, the wound healing breaking strength, the wound size, and the contraction percent were evaluated. Six rats in each group were euthanized at each time point for histopathological, immunohistochemical examination of collagen, the levels of alpha-smooth muscle actin (α-SMA), and epidermal growth factor receptor (EGFR). additionally, the gene expression analysis of the relative renal nuclear factor erythroid 2-related factor2 (Nrf2 mRNA), Transforming growth factor beta-1 (TGFβ1), fibroblast growth factor-7 (FGF7), Transforming growth factor beta-1 (TGFβ1), Lysyl oxidase (LOX), and Vascular endothelial growth factor (VEGF) were applied. ResultsThe Exo-group exhibited a significant decrease in wound size and a significant increase in wound contraction compared with other groups. Histopathologically evaluation during the three intervals revealed that the Exo-group had the highest collagen deposition area with a significant reduction of the granulation tissue. Moreover, upregulated gene expression profiles of the growth factors genes at all time points post-wounding. DiscussionThe exosomes-treated group revealed superior wound healing and contraction, with minimal inflammatory signs, higher angiogenesis, and myofibroblasts, and associated with higher growth factor expression genes compared to the other groups. ConclusionsExosome-based therapy demonstrates potential as a treatment method to promote and accelerate wound healing by modulating angiogenesis, re-epithelialization, collagen deposition, and gene expression profiles.

Protocol for the Implantation of Scaffolds in a Humanized Mouse Cutaneous Excisional Wound Healing Model.

Tissue-engineered constructs combine the mechanical properties of biomaterials with biological agents to serve as scaffolds that direct the wound-healing process and promote tissue regeneration. A limitation to studying wound healing in vivo is that mouse skin contracts to heal rather than exhibiting granulation tissue formation and epithelialization like human skin. Therefore, it became necessary to develop a mouse model to better recapitulate human wound healing. The first splinted excisional wound healing model in mice, described in 2004, utilized silicone splints to prevent skin contracture.This model has been used to test a variety of wound healing strategies; however, to our knowledge, this model has not been adapted to test the effect of implants on wound healing. In our established protocol, circular bilateral excisional wounds are made on the mouse's dorsum. A circular implant made of porous polyethylene is sutured to the skin within the wound. A thin, donut-shaped silicone splint is secured to the skin surrounding the wound, and a thick, donut-shaped splint is placed on top to tent the wound dressing. Finally, the mouse's abdomen is wrapped in a bandage and tape toprotect the implants. Our protocol offers a significant enhancement to the existing model by enabling the testing of implants for wound healing, as well as using an additional splint that prevents direct contact between the wound dressing and the wound bed. This model can be used to study tissue-engineered implant designs in a relatively low-cost, simple, and high-throughput manner before advancing to larger animal studies. Key features • Builds up on methods developed by Galiano et al. [1] and extends their application to include scaffold testing. • Utilizes a construct that protects wounds, thereby enabling unaffected wound healing. • Can be adapted to test a wide variety of biomaterials for wound healing. • Describes dressing details and exact methodologies that prevent animals from interfering with wound healing.

Functional poly(e-caprolactone)/SerMA hybrid dressings with dimethyloxalylglycine-releasing property improve cutaneous wound healing

Medical dressings with multifunctional properties, including potent regeneration capability and good biocompatibility, are increasingly needed in clinical practice. In this study, we reported a novel hybrid wound dressing (PCL/SerMA/DMOG) that combines electrospun PCL membranes with DMOG-loaded methacrylated sericin (SerMA) hydrogel. In such a design, DMOG molecules are released from the hybrid dressing in a sustained mannerin vitro. A series ofin vitroassays demonstrated that DMOG-loaded hybrid dressing has multiple biological functions, including promotion of human umbilical vein endothelial cells proliferation and migration,in vitrovascularization, and the generation of intracellular NO. When applied to the cutaneous wound, the PCL/SerMA/DMOG dressing significantly accelerated wound closure and tissue regeneration by promoting angiogenesis in the wound area, collagen deposition, and cell proliferation within the wound bed. These results highlight the potential clinical application of PCL/SerMA/DMOG hybrid dressings as promising alternatives for accelerating wound healing via improved biocompatibility and angiogenesis amelioration.

Melatonin and Bacterial Cellulose Regulate the Expression of Inflammatory Cytokines, VEGF, PCNA, and Collagen in Cutaneous Wound Healing in Diabetic Rats.

The poor healing of diabetic wounds is characterized by prolonged inflammation and decreased collagen deposition. Diabetic patients exhibit changes in the plasma concentrations of pro-inflammatory cytokines, and the role of specific dressings may have an impact on healing. This study aims to evaluate the effects of a combined treatment comprising a bacterial cellulose dressing and melatonin application on the regulation and expression of inflammatory cytokines, VEGF, PCNA, and collagen in the healing of cutaneous wounds of diabetic rats. Pro-inflammatory cytokines, including IL-6, TNF-α, and VEGF, along with PCNA and type I and III collagen, were evaluated after 14 days. Immunohistochemistry showed decreased levels of IL-6, TNF-α, and VEGF, along with an increased expression of PCNA and type I collagen, in the groups treated exclusively with melatonin and bacterial cellulose associated with melatonin compared to the control and the commercial healing agent. It was concluded that treating the skin lesions of diabetic animals supplemented with melatonin using a bacterial cellulose-based dressing has positive effects in regulating the expression of inflammatory cytokines, vascular endothelial growth factor, and collagen, showing that this association could be a viable therapy approach in wound healing.

Immunohistochemical Expression of Tumor Necrosis Factor Like Weak Inducer of Apoptosis (TWEAK) in Cutaneous Wound Healing

Immunohistochemical Expression of Tumor Necrosis Factor Like Weak Inducer of Apoptosis (TWEAK) in Cutaneous Wound Healing

Jagged-1+ skin Tregs modulate cutaneous wound healing

Skin-resident regulatory T cells (Tregs) play an irreplaceable role in orchestrating cutaneous immune homeostasis and repair, including the promotion of hair regeneration via the Notch signaling ligand Jagged-1 (Jag1). While skin Tregs are indispensable for facilitating tissue repair post-wounding, it remains unknown if Jag1-expressing skin Tregs impact wound healing. Using a tamoxifen inducible Foxp3creERT2Jag1fl/fl model, we show that loss of functional Jag1 in Tregs significantly delays the rate of full-thickness wound closure. Unlike in hair regeneration, skin Tregs do not utilize Jag1 to impact epithelial stem cells during wound healing. Instead, mice with Treg-specific Jag1 ablation exhibit a significant reduction in Ly6G + neutrophil accumulation at the wound site. However, during both homeostasis and wound healing, the loss of Jag1 in Tregs does not impact the overall abundance or activation profile of immune cell targets in the skin, such as CD4+ and CD8+ T cells, or pro-inflammatory macrophages. This collectively suggests that skin Tregs may utilize Jag1-Notch signalling to co-ordinate innate cell recruitment under conditions of injury but not homeostasis. Overall, our study demonstrates the importance of Jag1 expression in Tregs to facilitate adequate wound repair in the skin.

Comparison of different modern wound dressings on full-thickness murine cutaneous wound healing with wild-type and type-2 diabetes db/db mice

BackgroundTo evaluate the process of cutaneous wound healing, experiments have been conducted. However, to date, what modern wound dressings are suitable remains unclear. Therefore, this study aimed to compare the healing process in different modern wound dressings to determine their suitability in experimental acute wound and chronic diabetic wound. Materials and methodsTwelve C57BL/6J mice and eleven db/db mice were subjected to full-thickness wound injuries. The mice were divided into the following four groups: hydrocolloid, form, film, and gauze groups in both wild-type and db/db mice. Wound healing was assessed until day 14. ResultsIn the wild-type groups, all wounds were healed and completed re-epithelialization by day 14. However, the wound surface was dry, and the periwound was hypercontracted in the wild-type–form and wild-type–gauze groups. In the db/db groups, wounds were not healed until day 14. Wound exudates in the db/db- hydrocolloid group were abundant and gradually increased until day 14. Wound exudates in the db/db-film group were present until day 14. Conversely, in the db/db-form and db/db-gauze groups, the wound surface was dry, and the periwound was hypercontracted. ConclusionThese results showed that hydrocolloid and film dressings are suitable modern wound dressings for the mice wound models of acute wound and chronic diabetic wound. Moreover, using either hydrocolloid or film dressing depending on the purpose of the study on cutaneous wound healing in diabetes is necessary.

Type III Collagen Regulates Matrix Architecture and Mechanosensing during Wound Healing

Post-natal cutaneous wound healing is characterized by development of collagen-rich scar lacking the architecture and functional integrity of unwounded tissue. Directing cell behaviors to efficiently heal wounds while minimizing scar formation remains a major wound management goal. Herein, we demonstrate type III collagen (Col3) as a critical regulator of re-epithelialization and scar formation during healing of Col3-enriched, regenerative (Acomys), scar-permissive (CD-1 Mus and wild-type Col3B6/B6 mice), and Col3-deficient, scar-promoting (Col3F/F, a murine conditional knockdown model) cutaneous wound models. We define a scar-permissive fibrillar collagen architecture signature characterized by elongated and anisotropically-aligned collagen fibers that is dose-dependently suppressed by Col3. Further, loss of Col3 alters how cells interpret their microenvironment - their mechanoperception - such that Col3-deficient cells display mechanically-active phenotypes in the absence of increased microenvironmental stiffness via upregulation and engagement of the profibrotic integrin α11. Further understanding Col3's role in regulating matrix architecture and mechanoresponses may inform clinical strategies that harness pro-regenerative mechanisms.

The Effects of Mesenchymal Stem Cells-Derived Exosomes on Metabolic Reprogramming in Scar Formation and Wound Healing.

Pathological scarring results from aberrant cutaneous wound healing due to the overactivation of biological behaviors of human skin fibroblasts, characterized by local inordinate inflammation, excessive extracellular matrix and collagen deposition. Yet, its underlying pathogenesis opinions vary, which could be caused by increased local mechanical tension, enhanced and continuous inflammation, gene mutation, as well as cellular metabolic disorder, etc. Metabolic reprogramming is the process by which the metabolic pattern of cells undergoes a systematic adjustment and transformation to adapt to the changes of the external environment and meet the needs of their growth and differentiation. Therefore, the abnormality of metabolic reprogramming in cells within wounds and scars attaches great importance to scar formation. Mesenchymal stem cells-derived exosomes (MSC-Exo) are the extracellular vesicles that play an important role in tissue repair, cancer treatment as well as immune and metabolic regulation. However, there is not a systematic work to detail the relevant studies. Herein, we gave a comprehensive summary of the existing research on three main metabolisms, including glycometabolism, lipid metabolism and amino acid metabolism, and MSC-Exo regulating metabolic reprogramming in wound healing and scar formation for further research reference.

Enhanced wound healing properties of biodegradable PCL/alginate core-shell nanofibers containing Salvia abrotanoides essential oil and ZnO nanoparticles

Electrospun nanofibrous membranes, with their unique structural features, can potentially enhance wound healing through controlled delivery of active agents. Here, an innovative porous nanofibrous membrane was developed as a dressing patch with antibacterial and anti-inflammatory functionalities for cutaneous wound healing. Zinc oxide nanoparticles (ZnO NPs) and Salvia abrotanoides essential oil (SAEO) were incorporated into sodium alginate, which served as the shell. Poly(ε-caprolactone) was used as the core of coaxial electrospun wound dressing nanofibers (PCL/SA@ZnO/SAEO). With the addition of ZnO NPs and SAEO, the average diameter of nanofibers was 187 ± 51 nm, with improved tensile strength (4.7 ± 0.4 MPa), elongation at break (32.9 ± 2.1), and elastic modulus (21.4 ± 2.0). Concurrent application of ZnO NPs and SAEO increased antimicrobial activity against Staphylococcus aureus and Escherichia coli and promoted the proliferation, attachment, and viability (>90 %) of L929 cells. The PCL/SA@ZnO/SAEO scaffold accelerated the healing time with total wound healing over 14 days in mouse models carrying full-thickness wounds compared to the nanofibrous scaffold without additives. Histopathological examinations demonstrated better tissue regeneration, i.e., enhanced collagen deposition, improved re-epithelialization, and neovascularization, and increased quantity of hair follicles. Moreover, the chicken chorioallantoic membrane assay confirmed the synergistic angiogenic effects of SAEO and ZnO NPs. Finally, the in vitro and in vivo results proposed the bioactive core-shell nanofibers synthesized as encouraging wound dressing materials for hastening the healing of cutaneous wounds.