Phyto-fabricated gold nanoparticles and heterologous platelet-rich fibrin potentiates cutaneous wound healing dynamics in canines.

While the effect of hyperglycemia on cutaneous wound healing is well recognized, the impact of high-glucose (HG) environment on UVB-induced skin tumor formation remains inconclusive. Similar to impaired wound healing, skin tumor formation involves keratinocyte proliferation and migration. Intriguingly, SOX2 has been recognized to play an important role in both wound healing and UVB-induced skin tumor formation by modulating cell proliferation and migration. As hyperglycemia results in impaired cutaneous wound healing, we hypothesized that the HG environment also impacts UVB-induced tumor formation of the skin. This study aimed to explore the effects of HG environment on epidermal keratinocytes, focusing on the impact of UVB-induced cell proliferation and migration via SOX2 expression. In cultured keratinocytes, HG-cultivated keratinocytes showed reduced SOX2 levels compared to control with or without UVB treatment. SOX2 regulates keratinocyte migration and proliferation via modulation of AKT phosphorylation. Additionally, O-linked-N-acetylglucosamine glycosylation contributed to reduced SOX2 levels in HG-cultivated keratinocytes. Animal studies demonstrated that diabetic mice skin has significantly less UVB-induced tumor formation, epidermal thickening, SOX2, and pAKT expression than the control mice; mutant p53 expression was also lower in diabetic mice but did not reach statistical significance compared to control. In conclusion, HG environment reduces UVB-induced keratinocyte proliferation and migration, in association with decreased SOX2 expression and downstream AKT signaling. The current findings provide novel insights regarding UVB-induced skin tumor formation of skin in patients with diabetes.

Refractory wounds are complicated multistep biological processes that can lead to severe complications in patients. Selective autophagy plays a crucial role in precisely controlling the quality of intracellular components and regulating biological behavior. This review explores the features and underlying mechanisms of various types of selective autophagy and highlights their implications in burn injury and wound healing. In-depth studies have underscored the critical role of selective autophagy, including mitophagy, endoplasmic reticulum (ER)-phagy, pexophagy, xenophagy, lysophagy, ferritinophagy, and lipophagy, in effectively controlling the quality of intracellular components and regulating biological behavior, which may enhance wound-healing process. Autophagy is a housekeeping and self-renewal process that utilizes lysosomal machinery to degrade and recycle cellular components, thereby enhancing cellular adaptability to stressful conditions. In addition to nonselective bulk degradation, autophagy selectively recycles specific cell constituents, including mitochondria, ER, peroxisomes, pathogens, lysosomes, lipid droplets, and ferritin. The effective management of the quality of cellular components during wound healing remains a challenge in clinical practice. Understanding the basic mechanisms and intricate crosstalk underlying selective autophagy may facilitate the development of comprehensive strategies and therapeutic targets for wound healing.

Plant and herbal preparations are traditionally used in wound management to promote healing. The study aimed to explore the therapeutic efficacy of Lajjabati (Mimosa pudica) leaves and Daruchini (Cinnamomum verum) paste on wound healing and the histo-architectural changes in the wounded skin of rabbits. Sixteen rabbits, weighing between 1.5 and 2 kg, were divided into four groups: A, B, C, and D, each containing 4 rabbits. Surgical incisions were made on the skin of the rabbits, creating a total of 32 wounds, two for each rabbit. Lajjabati (Mimosa pudica) leaves, Daruchini (Cinnamomum verum) paste, and a combination were applied to the skin wounds in Groups A, B, and C, respectively. Group D was considered the control. The morphological characteristics of wound healing, such as the swelling of sutured areas, elevation of the suture line, width of the sutured area, and contraction length, were recorded from Day 0 to Day 21. Bacteriological and histopathological samples were collected on Day 3, 7, and 14 for analysis. The swelling of the sutured area and elevation of the sutured line were 11.50 ± 0.13 and 2.54 ± 0.10 mm in Group A, which were significantly lower compared to other groups. The histopathological study revealed the presence of marked inflammation, hyperplasia, and enlargement of glands in Groups B and C, whereas in Group A, all tissues appeared to be normal, and hair follicles started to grow on Day 7. In microbiological study, the lowest bacterial colonies were observed in Group A. It is concluded that Lajjabati (Mimosa pudica) paste is more effective in the wound healing process. Daruchini (Cinnamomum verum) can also be used, but it causes more tissue reactions, indicating delayed healing of cutaneous wounds.

High-frequency ultrasound (HFUS) allows non-invasive visualization of skin microarchitecture, offering quantitative assessment of dermal composition and vascularity, but its systematic use to track temporal changes in postoperative wound healing is still limited. This study aimed to describe and validate HFUS morphologic and vascular features corresponding to the biological phases of cutaneous surgical wound healing. A total of 730 patients who underwent surgical excision of skin lesions were evaluated at different postoperative intervals using high- and ultra-high-frequency ultrasound (48-70 MHz). Dermal thickness, echogenicity and vascularity were analysed with B-mode and colour Doppler imaging through quantitative and semi-quantitative methods and reproducibility was assessed using intraclass correlation coefficients (ICC) and Cohen's κ statistics. Cross-sectional analysis demonstrated a progressive structural and vascular evolution consistent with canonical healing phases: dermal thickness decreased from 2.45 ± 0.38 mm at T0 to 1.58 ± 0.21 mm at T4, while echogenicity increased from 0.5 [0-1] to 2.5 [2, 3], reflecting collagen compaction and maturation. Vascularity peaked at T2 (2.2 ± 0.5) and declined to 0.8 ± 0.3 by T4, paralleling the regression of angiogenesis. Measurement reproducibility was excellent (ICC = 0.91; κ = 0.82). HFUS morphologic patterns closely mirrored the biological sequence from inflammatory oedema through granulation and fibroplasia to collagen remodelling, providing real-time invivo correlates of tissue repair. These findings support HFUS as a reliable, quantitative and reproducible tool for monitoring postoperative wound healing and as a potential imaging biomarker framework for early detection of abnormal scar evolution.

The effect of intradermal botulinum toxin type A injection on healing of porcine full-thickness wounds.

Topical Effects of a Combination of Bitter Melon (Momordica charantia) and Tamarind (Tamarindus indica) Leaf Extracts on Cutaneous Wound Healing in Female Wistar Rats

Stapled peptide inhibitors target VGLL4/TEAD4 interactions to accelerate cutaneous wound healing.

Intermittent Hypoxia Accelerates Full-Thickness Cutaneous Wound Healing in Sprague-Dawley Rats: The Role of Upregulated TGF-β and YAP Expression

ABSTRACTBackgroundOptimizing cutaneous wound healing remains a priority in dermatology and plastic surgery. Bioactive injectables such as NCTF and VAMP are gaining interest for their potential to enhance angiogenesis and tissue regeneration, yet their combined effects remain underexplored.ObjectiveTo compare the effects of NCTF, VAMP, and their combination on full thickness skin wound healing in an experimental hamster model, using histological and immunohistochemical analyses.MethodsOne hundred forty‐four adult hamsters were randomly assigned to four groups: (1) control (full thickness 2 cm length & 2 mm width dorsal incision, no injection), (2) NCTF (0.1 mL), (3) VAMP (0.1 mL), and (4) combined NCTF + VAMP (0.05 mL each). Wounds were evaluated at baseline, day 3, day 7, and day 14. Tissue samples underwent hematoxylin–eosin (HE) and Masson's trichrome (MT) staining for histological assessment, and immunohistochemical staining for CD34 was performed to evaluate angiogenesis and capillary density.ResultsAll treatment groups showed faster wound closure, greater collagen deposition, and higher microvessel density than controls. The combination therapy produced the most pronounced improvements, followed by NCTF alone, then VAMP alone, with the control group showing the slowest healing. CD34 positive capillary density and collagen fiber alignment were significantly superior in the combination group at days 7 and 14 (p < 0.05).ConclusionNCTF and VAMP both enhance full thickness skin wound healing, with the combination achieving the greatest histological and angiogenic improvements. These findings pertain to early and intermediate phases of wound healing (up to 14 days) and suggest potential benefit of combination therapy, pending further studies in larger animal models and clinical trials.

Salidroside derivative SHPL-49 accelerates cutaneous wound healing in diabetic mice by modulating macrophage-mediated TGF-β1/Smad2/3 signaling pathway.

Wound healing is a regenerative process that restores damaged connective tissue, but inadequate management can delay repair. Sodium alginate may promote wound healing by modulating oxidative stress through its antioxidant, antimicrobial, and immunomodulatory properties. This study aimed to evaluate the effectiveness of alginate in supporting wound healing using zebrafish as an experimental model. Alginate oligosaccharides (AOS) were produced by oxidative depolymerization of crude alginate using hydrogen peroxide and ascorbic acid. Zebrafish with induced cutaneous wounds were immersed in AOS solutions at concentrations of 350, 500, 650, and 800 ppm. Each treatment consisted of 20 randomly assigned fish and was conducted in triplicate. Immersion treatments were administered at three time points: 12 h before wound induction, after wound induction, and on the fourth day post-injury. Each immersion exposure lasted for 1 h. Biological responses were evaluated using a zebrafish cutaneous wound model. Alginate oligosaccharide (AOS) treatments (350-800 ppm) accelerated early wound healing, with higher wound closure on day 4 (6.67 ± 2.89-8.33 ± 2.89%) compared to the control (0%). The highest closure was observed at 500 and 800 ppm, although no clear dose-dependent or statistically significant differences were detected. Complete wound closure occurred in all groups by day 21. Overall, the findings indicate that alginate oligosaccharide treatment was well tolerated and compatible with the wound-healing process, supporting its further evaluation as a marine-derived biomaterial.

Efficient generation of bioactive and structurally preserved decellularized extracellular matrix (dECM) is critical for regenerative medicine applications. Conventional decellularization techniques, however, frequently utilize detergents such as sodium dodecyl sulfate and Triton X-100, which may compromise ECM integrity, diminish retention of bioactive components and impair mechanical properties. To address these limitations, we present a supercritical CO2 (scCO2)-assisted co-solvent strategy for efficient decellularization of porcine dermis, yielding a bioactive acellular dermal matrix (ADM) patch with high clinical potential in cutaneous wound healing. Porcine dermal sheets were first subjected to scCO2-ethanol co-solvent treatment (28 MPa, 40°C, 6 h) followed by rapid depressurization. The solvent system was then switched to scCO2-water co-solvent with concurrent ultrasonic washing. After subsequent depressurization, pure scCO2 was introduced to achieve supercritical drying. Compared with detergent-based methods, scCO2-derived ADM demonstrated enhanced retention of bioactive components and superior mechanical properties. In vitro experiments demonstrated excellent biocompatibility, promoting L929 cell proliferation and migration, with minimal cytotoxicity and low apoptosis rates. In a full-thickness skin defect model in mice, the scCO2-derived ADM accelerated wound closure, enhanced collagen deposition and significantly improved angiogenesis and ECM remodeling. Overall, this scCO2-based decellularization approach provides a robust, efficient and environmentally friendly platform for preparing high-performance dECM scaffolds, offering promising prospects for clinical applications in skin regeneration.

Adult stem cells and their niches communicate intricately for tissue maintenance and regeneration. However, effectively coordinating these complex interactions is challenging. Here, we demonstrate that transient dedifferentiation of a fraction of epithelial stem cell progenies orchestrates beneficial changes within the entire skin's cellular networks to favor repair. We achieved this by inducing a mosaic and reversible expression of reprogramming factors (Oct-4, Sox2, Klf4, and c-Myc) in the mouse epidermis. This in vivo partial epidermal reprogramming not only affected the partially reprogrammed cells, but also their microenvironment, including neighboring epithelial cells and T cells, conferring widespread healing characteristics even in the absence of injury. When a wound was introduced, these collective changes accelerated re-epithelialization in both wild-type and a hyperglycemic mouse disease model. Furthermore, the effects extended to dermal healing, leading to reduced scarring and altered angiogenesis. In conclusion, our work reveals that mosaic partial reprogramming of the epidermis influences various cell types within the skin during homeostasis and repair, leading to enhanced cutaneous wound healing.

The failure of conventional therapies for diabetic wounds, including those relying solely on stem cells or antioxidants, stems from an inability to simultaneously overcome the hostile microenvironment characterized by chronic inflammation, excessive apoptosis, and impaired regeneration. We developed a novel combinatorial platform, Ru@SVF, by integrating ruthenium nanozymes (RuNC) with a stromal vascular fraction gel (SVF-GEL). This design moves beyond simple material addition, aiming for synergy: RuNC provides potent reactive oxygen species (ROS) scavenging and anti-apoptotic signaling, while SVF-GEL ensures sustained release of pro-regenerative growth factors (VEGF, EGF, bFGF). After thorough physicochemical characterization and biocompatibility assessment, its mechanism and efficacy were evaluated in vitro and in a diabetic rat model. Ru@SVF exhibited excellent biocompatibility and superior functionality. In vitro, it not only robustly suppressed inflammation and mitochondrial apoptosis (via Bax/Bcl-2/Caspase-3,9 regulation) in HUVECs but also enhanced the secretion of key growth factors. In vivo, Ru@SVF treatment led to significantly accelerated wound closure, which was accompanied by reduced apoptosis, diminished inflammatory infiltration, and promoted angiogenesis, outperforming treatments with either RuNC or SVF-gel alone. The Ru@SVF composite represents a significant advance by synergistically integrating catalytic nano-therapy with functional cell delivery. Its capacity to concurrently resolve inflammation, prevent apoptosis, and activate reparative signaling within a single platform addresses the multifaceted pathology of diabetic wounds more effectively than single-target strategies, offering a novel and promising therapeutic paradigm.

Dermatomyositis (DM) is an idiopathic inflammatory myopathy (IIM) characterized by distinctive chronic cutaneous manifestations. Although immune-mediated and microvascular mechanisms are well established, the role of metabolic dysfunction, particularly hyperglycemia, is underexplored in dermatological conditions. This review synthesizes mechanistic, clinical, and translational evidence to explore the relationship between dysglycemia and cutaneous disease severity in DM. Hyperglycemia is associated with oxidative stress, advanced glycation end-product formation, endothelial injury, and proinflammatory cytokine signaling. These processes may plausibly amplify DM-associated vasculopathy, impair wound healing, and worsen cutaneous inflammation. Limited DM-specific studies demonstrate increased insulin resistance and a higher prevalence of diabetes compared with healthy controls. Meanwhile, case reports suggest that poor glycemic control can exacerbate cutaneous disease. Evidence from other inflammatory dermatoses supports a biologically plausible role for dysglycemia in increasing flare frequency, infection risk, and delayed tissue repair. Dietary patterns characterized by high glycemic index and coexisting metabolic syndrome may further intensify systemic and cutaneous inflammation. Collectively, these findings suggest hyperglycemia as a biologically plausible contributor to cutaneous disease severity in DM that warrants further investigation. These observations highlight the need for future studies to evaluate whether metabolic screening, dietary patterns, and interdisciplinary care influence cutaneous disease activity and wound healing in DM. Prospective clinical investigation is needed to determine whether targeted glycemic optimization is associated with changes in cutaneous and systemic outcomes in DM.

BackgroundAdipose‐derived mesenchymal stem cells (ADSCs) have great potential in the realm of tissue repair and regenerative medicine. However, the exact effects of ADSCs on the healing of skin wounds and the underlying mechanisms remain unexplored. Here, we investigated the effects of ADSCs on fibroblasts and keratinocytes and their related molecular mechanisms in wound healing.MethodsWe used a murine model in vivo and a Transwell coculture system in vitro. The proliferation and migration abilities of human dermal fibroblasts (HDFs) and human immortalized keratinocytes (HaCaT) were analyzed after coculture with ADSCs, and the target molecules were investigated by transcriptome sequencing. We further investigated phenotypic changes by knocking down and overexpressing the target molecule and analyzed the potential mechanisms.ResultsWe successfully extracted, expanded, and identified ADSCs. ADSCs not only accelerated wound healing in mice but also improved healing quality. Coculture with ADSCs augmented the proliferation and migration capacities of main skin cells in vitro. RNA sequencing analysis revealed that the level of serpin family E member 1 (SERPINE1) in both HDF and HaCaT was significantly regulated by ADSCs. Knockdown of SERPINE1 restrained the proliferation and migration phenotypes of HDF and HaCaT, while overexpression of SERPINE1 did exactly the opposite. Pathway enrichment analysis revealed that SERPINE1 was mainly related to PI3K‐Akt and MAPK signaling pathways.ConclusionThe in vivo model and in vitro cell test demonstrate that ADSC effectively promotes cutaneous wound healing by augmenting the proliferation and migration of fibroblasts and keratinocytes through upregulating SERPINE1, which provides novel insights into the biological roles of SERPINE1 in wound healing and suggests ADSC has a promising future in skin injury therapy.

Abstract Introduction and aims N6-methyladenosine (m6A) RNA modification has been implicated in key cutaneous physiological processes, including differentiation, inflammation, immunity, and wound healing. We sought to explore m6A regulation in the setting of severe epidermolysis bullosa simplex (EBS), a rare inherited keratinopathy biologically characterized by disruption of keratin intermediate filament networks within basal keratinocytes, keratin aggregation, cytolysis and persistent inflammation that compounds impaired keratin cycling. This gives rise to skin fragility and persistent wounds, frequently exerting devastating impacts on quality of life. Despite its established relevance in other dermatoses, the role of m6A in EBS has yet to be explored. Methods We investigated the gene expression of key proteins involved in m6A regulation (writers, readers, and erasers) as well as overall RNA m6A levels in KEB-7 cells (KRT14 R125P) derived from a patient with severe autosomal dominant EBS. NEB-1 cells, derived from a healthy donor, served as controls. Analyses were performed using mRNA sequencing, quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), and RNA m6A colorimetry assay. Results Differential gene expression analysis of KEB-7 cells showed upregulation of the m6A writer METTL14 and readers YTHDC1, YTHDF2, and YTHDF3. Downregulation of the reader YTHDF1 and the eraser FTO was also observed. qRT-PCR validated the significant upregulation of METTL14 and YTHDC1 and downregulation of FTO. Total RNA m6A levels were elevated in KEB-7 cells compared with NEB-1 cells. We hypothesize that m6A dysregulation modulates the phenotype observed in severe EBS. Conclusions This pilot study identifies m6A RNA methylation dysregulation as a potential modifier of genotype–phenotype correlation in severe EBS. These findings align with existing evidence supporting the role of m6A in inflammation and immune regulation. Targeted m6A level regulation using activators or inhibitors of writers, erasers and readers may impact T-cell regulation, promote keratinocyte migration, and attenuate deleterious inflammatory responses with potential to improve wound management and quality of life in EBS.

Angiogenesis plays a pivotal role in cutaneous wound healing by restoring vascular supply to regenerating tissues. Mesenchymal stem cell-derived exosomes (MSC-exosomes) are emerging as potent acellular mediators of angiogenesis, thanks to their cargo of bioactive molecules and immunomodulatory effects. This review synthesizes recent findings from in vivo and in vitro studies, including preclinical models of diabetic wounds, ischemic injuries, and burn healing. It draws upon peer-reviewed articles published in biomedical journals, with a focus on the mechanisms and efficacy of MSC-exosomes. MSC-derived exosomes enhance endothelial cell proliferation, migration, and tube formation. Their ability to activate pro-angiogenic signaling pathways, such as Wnt/β-catenin, AKT/eNOS, and angiopoietin/TIE2, is widely accepted. Additionally, their low immunogenicity, enhanced stability, and potential for bioengineered delivery systems are recognized advantages over other angiogenic therapies. Challenges persist regarding the standardization of exosome isolation, characterization, and large-scale production. Debate also exists about their long-term safety and therapeutic consistency across MSC sources. Incorporation of MSC-exosomes into hydrogels and scaffolds offers promising controlled delivery systems that enhance angiogenic efficacy. Preconditioning MSCs (e.g. with hypoxia or pharmacological agents) further improves the pro-angiogenic potency of exosomes. Future efforts should prioritize clinical translation by developing GMP-compliant production protocols, optimizing delivery strategies, and conducting rigorous clinical trials to assess safety, dosing, and therapeutic efficacy across diverse wound types.

Cutaneous wound healing consists of complex processes involving different types of cells and signalling pathways, and occurs in three phases (inflammatory, proliferative and tissue remodelling). The dysregulation of these processes leads to abnormal wound healing, manifesting as hard-to-heal (chronic) wounds at one extreme and pathological scarring at the other. Recent studies have shown that the tumour necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) signalling pathway regulates inflammatory, re-epithelialisation, collagen synthesis and angiogenesis processes, suggesting that it can modulate cutaneous wound healing. Despite numerous studies suggesting a relationship between the TWEAK/Fn14 axis and cutaneous wound healing, there has been little attention paid to this relationship to date. There is scarce direct evidence supporting that TWEAK/Fn14 axis-targeted therapies work in cutaneous wounds. This review summarises the evidence that TWEAK/Fn14 signalling is involved in wound repair as well as in tissue remodelling. In addition, TWEAK/Fn14 axis-targeted therapies in other diseases are highlighted, and their therapeutic potential in cutaneous wounds discussed.