Chronic non-healing wounds significantly impair patient rehabilitation and remain a critical clinical challenge. Stem cell-derived exosomes, owing to their biocompatibility and physiological activity, have emerged as a promising therapeutic approach in regenerative medicine. Beyond their intrinsic wound-healing properties, exosomes are increasingly explored as carriers for small-molecule drugs to enhance synergistic treatment effects. Although microRNAs (miRNAs) exhibit potential in promoting cell proliferation and re-epithelialization, their clinical application is hindered by poor stability. In this study, we investigated the therapeutic effects of miR-132-3p-loaded human umbilical mesenchymal stem cell-derived exosomes (miR-132-3p@UMSC-EXOs) on human foreskin fibroblast-1 (HFF-1). Our findings demonstrated that miR-132-3p@UMSC-EXOs significantly enhanced proliferation and migration of HFF-1, while reducing intracellular reactive oxygen species (ROS) levels compared with unloaded exosomes. Furthermore, qRT-PCR and Western blotting analyses revealed that miR-132-3p@UMSC-EXOs modulated the expression of genes associated with extracellular matrix (ECM) remodeling and inflammation, suggesting their potential to upregulate collagen synthesis and improve ECM metabolism. These results highlight the therapeutic promise of miR-132-3p@UMSC-EXOs in accelerating wound healing.
Humans ; MicroRNAs/pharmacology* ; Exosomes/metabolism* ; Mesenchymal Stem Cells/cytology* ; Wound Healing ; Umbilical Cord/cytology* ; Cell Proliferation ; Fibroblasts/cytology* ; Skin/injuries* ; Cell Movement ; Reactive Oxygen Species/metabolism* ; Cells, Cultured

OBJECTIVES: To evaluate the photothermal and antibacterial activities of polydopamine-modified phycocyanin nanoparticles (PDA@PC NPs) and their capacity for promoting wound healing. METHODS: PDA@PC NPs were synthesized from phycocyanin (C-PC) and dopamine hydrochloride using a one-pot method. The photothermal activity of the nanoparticles was assessed in vitro by 808 nm laser irradiation, their biocompatibility was evaluated using CCK-8 assay, and their photothermal antibacterial activity by plate colony counting. In adult male BALB/c mice, two symmetrical full-thickness skin wounds (1.0 cm ×1.0 cm) were created on both sides of the spine, and 200 μL of Staphylococcus aureus suspension was inoculated into the wounds. The mice were divided into control group, PDA@PC NPs group, and PDA@PC NPs with laser irradiation group, and wound healing rates and histomorphological changes in the wound tissues were evaluated on days 0, 7 and 14 after modeling. RESULTS: The synthesized PDA@PC NPs exhibited no obvious cytotoxicity up to a concentration of 500 μg/mL and showed strong photothermal and antibacterial activities in response to 808 nm laser irradiation. In the mouse models, the size of the infected skin wounds showed substantial reduction at 7 and 14 days in PDA@PC NPs group and PDA@PC NPs with laser irradiation group, and the mean wound healing rate was faster in the latter group. HE staining and Masson's trichrome staining revealed extensive granulation tissue formation and collagen deposition on the wound surfaces in both of the treatment groups, and these changes were more obvious in the PDA@PC NPs with laser irradiation group. CONCLUSIONS PDA@PC NPs possess excellent photothermal and antibacterial activities and can effectively promote wound healing in mice.
Animals ; Indoles/chemistry* ; Wound Healing/drug effects* ; Mice ; Mice, Inbred BALB C ; Male ; Nanoparticles ; Polymers/chemistry* ; Phycocyanin/chemistry* ; Skin/injuries* ; Staphylococcus aureus/drug effects* ; Anti-Bacterial Agents/pharmacology*

OBJECTIVES: To evaluate the clinical efficacy of human biological dressing (human acellular dermal matrix) transplantation in the management of refractory wounds among middle-aged and elderly patients. METHODS: A retrospective observational study was conducted involving 104 middle-aged and elderly patients (74 males, 30 females; aged 56-95 years) with refractory wounds treated at the First Affiliated Hospital of Wenzhou Medical University from January 2023 to December 2024. Following debridement, wound areas ranged from 1.0 to 48.0 cm². All patients received vacuum sealing drainage for 7 days, followed by human biological dressing transplantation. Subsequently, depending on the wound condition and the patient's preference, autologous skin grafting (ASG) or wound dressing changes were employed to promote wound healing. Outcome measures included: post-human biological dressing coverage of exposed tendons/bones and occurrence of tendon infection/osteomyelitis; survival rate of ASG at postoperative day 7; healing time in patients managed with wound dressing changes alone; patient satisfaction; and changes in pain intensity, sleep disturbance, and anxiety scores assessed before and 1 month after human biological dressing transplantation using the Edmonton Symptom Assessment Scale. RESULTS: After human biological dressing transplantation, 103 patients exhibited robust granulation tissue formation achieving complete coverage of the exposed tendons/bones, with no instances of tendon/bone necrosis, infection, or osteomyelitis. Among these, 51 patients underwent successful ASG at (44.4±13.0) d post-human biological dressing transplantation (success rate 100.00%), 52 patients achieved primary wound healing through dressing changes alone within (62.6±13.4) d post-human biological dressing transplantation. One patient experienced human biological dressing dissolution and detachment due to gluteal wound infection, resulting in non-healing. The overall cure rate was 99.04%. Patient satisfaction survey showed that 95 patients were very satisfied, 8 were satisfied, and 1 was dissatisfied (satisfaction rate 99.04%). Pain, sleep disturbance, and anxiety scores at 1 month post-human biological dressing transplantation were significantly reduced compared to pre-transplantation scores (all P<0.05). CONCLUSIONS Human biological dressing transplantation demonstrate excellent outcomes in treating refractory wounds in middle-aged and elderly patients and can serve as an effective therapeutic strategy for managing refractory wounds.
Humans ; Aged ; Male ; Middle Aged ; Female ; Aged, 80 and over ; Retrospective Studies ; Wound Healing ; Biological Dressings ; Skin Transplantation ; Acellular Dermis ; Wounds and Injuries/surgery* ; Treatment Outcome

Skin wound repair is critically regulated by peripheral nerves. Injury or dysfunction of these nerves represents a key factor impairing the healing of pathological wounds, such as diabetic ulcers and deep burns. The mechanisms by which peripheral nerves participate in cutaneous wound healing primarily involve modulation of immune responses, construction of stem cell niches, and promotion of angiogenesis. Sensory neurons initiate and mediate essential local immune responses, contribute to the epidermal stem cell microenvironment, and support regenerative potential. Sympathetic nerves bidirectionally regulate immune homeostasis via the release of various neuromodulators and precisely control the activation of hair follicle stem cells as well as the homeostasis of melanocyte stem cells. Schwann cells also play pivotal roles in immune modulation, balancing repair processes and mitigating scar formation. During revascularization, sensory and autonomic nerve terminals release neurotransmitters that precisely regulate vasomotor activity and angiogenesis, while Schwann cells facilitate the reconstruction of functional vascular networks via potent paracrine signaling. This review systematically summarizes the crucial roles of peripheral nerves in skin wound repair, with emphasis on their regulatory mechanisms in immune responses, stem cell activation and homeostasis, and vascular dynamics, thereby providing insights into the development of novel therapeutic strategies targeting peripheral nerve regulation.
Humans ; Wound Healing/physiology* ; Peripheral Nerves/physiology* ; Schwann Cells/physiology* ; Skin/injuries* ; Animals

N,N-Dimethylglycine (DMG) is a glycine derivative, and its sodium salt (DMG-Na) has been demonstrated to possess various biological activities, including immunomodulation, free radical scavenging, and antioxidation, collectively contributing to the stability of tissue and cellular functions. However, its direct effects and underlying mechanisms in wound healing remain unclear. In this study, a full-thickness excisional wound model was established on the dorsal skin of mice, and wounds were treated locally with DMG-Na. Wound healing progression was assessed by calculating wound closure rates. Histopathological analysis was conducted using hematoxylin-eosin (HE) staining, and keratinocyte proliferation, migration, and differentiation were evaluated using CCK-8 assays, scratch wound assays, and quantitative reverse transcription PCR (qRT-PCR). Inflammation-related cytokine expression in keratinocytes was analyzed via ELISA and qRT-PCR. Results revealed that DMG-Na treatment significantly accelerated wound healing in mice and improved overall wound closure quality. The wound healing rates on days 3, 6, and 9 were 49.18%, 68.87%, and 90.55%, respectively, with statistically significant differences compared to the control group ( P<0.05). DMG-Na treatment downregulated the mRNA levels of keratinocyte differentiation markers while enhancing cell proliferation and migration ( P<0.05). Furthermore, DMG-Na decreased the secretion of LPS-induced keratinocyte inflammatory cytokines, including IL-1β, IL-6, IL-8, TNF-α, and CXCL10 ( P<0.05). These findings indicate that DMG-Na regulates inflammatory responses and promotes keratinocyte proliferation and migration, thereby facilitating the healing of skin wounds.
Animals ; Wound Healing/drug effects* ; Mice ; Cell Proliferation/drug effects* ; Keratinocytes/drug effects* ; Cell Movement/drug effects* ; Cell Differentiation/drug effects* ; Glycine/pharmacology* ; Skin/injuries* ; Male

OBJECTIVE: To investigate the effectiveness of delayed replantation of degloving skin preserved at 4℃ in treatment of limb degloving injuries. METHODS: Between October 2020 and October 2023, 12 patients with limb degloving injuries were admitted. All patients had severe associated injuries or poor wound conditions that prevented primary replantation. There were 7 males and 5 females; age ranged from 29 to 46 years, with an average of 39.2 years. The causes of injury included machine entanglement in 6 cases, traffic accidents in 5 cases, and sharp instrument cuts in 1 case. Time from injury to hospital admission was 0.5-3.0 hours, with an average of 1.3 hours. Injury sites included upper limbs in 7 cases and lower limbs in 5 cases. The range of degloving skin was from 5 cm×4 cm to 15 cm×8 cm, and all degloving skins were intact. The degloving skin was preserved at 4℃. After the patient's vital signs became stable and the wound conditions improved, it was trimmed into medium-thickness skin grafts for replantation. The degloving skin was preserved for 3 to 7 days. At 4 weeks after replantation, the viability of the degloving skin grafts was assessed, including color, elasticity, and sensation of pain. The Vancouver Scar Scale (VSS) was used to assess the scars of the skin grafts during follow-up. RESULTS: At 4 weeks after replantation, 8 cases of skin grafts completely survived and the color was similar with normal skin, with a survival rate of 66.67%. The elasticity of skin grafts (R0 value) ranged from 0.09 to 0.85, with an average of 0.55; moderate pain was reported in 4 cases, mild pain in 3 cases, and no pain in 5 cases. All patients were followed up 12 months. Over time, the VSS scores of all 12 patients gradually decreased, with a range of 4-11 at 12 months (mean, 6.8). CONCLUSION For limb degloving injuries that cannot be replanted immediately and do not have the conditions for deep low-temperature freezing preservation, the method of preserving the degloving skin at 4℃ for delayed replantation can be chosen.
Humans ; Male ; Adult ; Replantation/methods* ; Female ; Degloving Injuries/surgery* ; Middle Aged ; Skin Transplantation/methods* ; Treatment Outcome ; Extremities/injuries* ; Time Factors ; Skin/injuries* ; Tissue Preservation/methods*

OBJECTIVE: To explore the effectiveness of free paraumbilical perforator flaps in repairing skin and soft tissue defects in children. METHODS: Between February 2018 and March 2024, 12 children with skin and soft tissue defects were treated with the free paraumbilical perforator flaps. There were 7 boys and 5 girls with an average age of 6.3 years (range, 2-12 years). The defects located on the upper limbs in 6 cases, lower limbs in 5 cases, and neck in 1 case. The causes of wounds included 7 cases of electrical burns, 1 case of thermal burn, 2 cases of scar release and excision due to scar contraction after burns, 1 case of scar ulcer at the amputation stump after severe burns, and 1 case of skin necrosis after a traffic accident injury. The size of defects after debridement ranged from 7.0 cm×4.0 cm to 18.0 cm×10.0 cm. According to the defect size, 11 cases were repaired with unilateral paraumbilical perforator flaps centered on the umbilicus, among which 3 cases with larger defects were designed as "L"-shaped flaps along the lateral and lower ends of the perforator; the donor sites were directly closed. One case with extensive defect after scar excision and release was repaired with bilateral expanded paraumbilical perforator flaps; the donor sites were repaired with autologous split-thickness skin grafts. The size of flaps ranged from 9.0 cm×4.0 cm to 20.0 cm×11.0 cm. Postoperatively, analgesia and sedation were provided, and the blood supply of the flaps was observed. RESULTS: All operations were successfully completed. The operation time was 4-7 hours, with an average of 5.0 hours. After postoperative analgesia and sedation, the visual analogue scale (VAS) score for pain in all children was less than or equal to 3, and there was no non-cooperation due to pain. All flaps and skin grafts survived completely, and the wounds healed by first intention. Ten children underwent 1-4 times of flap de-fatting, finger separation, and trimming. All children were followed up 6-48 months (mean, 26.6 months). No obvious swelling of the flaps occurred, and the texture was soft. At last follow-up, among the 6 children with upper limb defects, 2 had upper limb function grade Ⅳ and 4 had upper limb function grade Ⅴ according to the Carroll upper limb function assessment method. The 4 children with lower limb defects had no limitation of joint movement. The neck flexion and rotation in the 1 child with neck defect significantly improved when compared with that before operation. The 1 child with residual ulcer at the amputation stump could wear a prosthesis and move without limitation, and no new ulcer occurred. Linear scars were left at the donor sites, and no abdominal wall hernia was formed. CONCLUSION The free paraumbilical perforator flap has abundant blood supply and can be harvested in large size. It can be used to repair skin and soft tissue defects in children and has the advantages of short operation time, minimal injury, high safety, and minimal impact on the growth and development of children.
Humans ; Perforator Flap/transplantation* ; Child ; Male ; Female ; Soft Tissue Injuries/surgery* ; Child, Preschool ; Plastic Surgery Procedures/methods* ; Burns/surgery* ; Umbilicus/surgery* ; Skin Transplantation/methods* ; Skin/injuries* ; Cicatrix/surgery* ; Treatment Outcome

OBJECTIVE: To explore the method and effectiveness of index finger proximal dorsal island flap supplied by the nutrient vessels of superficial branch of radial nerve for treatment of thumb skin and soft tissue defect. METHODS: Between August 2019 and December 2024, 12 patients with thumb skin and soft tissue defects caused by trauma accompanied by variation of the first dorsal metacarpal artery were treated. There were 8 males and 4 females, aged 19-55 years, with an average age of 32 years. The wound area ranged from 2.2 cm×2.0 cm to 5.5 cm×3.5 cm. The time from injury to operation ranged from 1.5 to 6.0 hours, with an average of 4.5 hours. After thorough debridement, the wound was repaired with a index finger proximal dorsal island flap supplied by the nutrient vessels of the superficial branch of the radial nerve. The flap area ranged from 2.4 cm×2.2 cm to 6.0 cm×4.0 cm. The donor site was repaired with free skin grafting. Regular follow-up was conducted postoperatively to observe the appearance, texture, sensory recovery of the flap, and the condition of the donor site. RESULTS: The operation time ranged from 30 to 72 minutes, with an average of 47 minutes; intraoperative blood loss ranged from 30 to 70 mL, with an average of 46 mL. After operation, partial necrosis occurred at the skin edge of the radial incision on the dorsum of the hand in 1 case, which healed after dressing changes; all other flaps survived uneventfully, with primary wound healing. The skin grafts at the donor sites all survived. All 12 patients were followed up 5-36 months, with an average of 14 months. The appearance and texture of the flaps were good. At last follow-up, the two-point discrimination of the flaps ranged from 4 to 9 mm, with an average of 5.2 mm. According to the functional evaluation criteria for upper limb issued by the Hand Surgery Society of Chinese Medical Association, the results were excellent in 11 cases and good in 1 case. No scar contracture, pain, or joint movement limitation was observed at the donor sites. CONCLUSION For patients with skin and soft tissue defects of the thumb accompanied by variation of the first dorsal metacarpal artery, the index finger proximal dorsal island flap supplied by the nutrient vessels of the superficial branch of the radial nerve can be selected. This method has advantages such as shorter operation time, less intraoperative bleeding, and good postoperative appearance and sensation of the flap.
Humans ; Male ; Adult ; Female ; Thumb/surgery* ; Soft Tissue Injuries/surgery* ; Radial Nerve/surgery* ; Middle Aged ; Surgical Flaps/innervation* ; Plastic Surgery Procedures/methods* ; Skin Transplantation/methods* ; Young Adult ; Treatment Outcome ; Fingers/surgery* ; Skin/injuries*

OBJECTIVE: To investigate the effectiveness and preliminary mechanisms of icariin (ICA) in enhancing the reparative effects of adipose-derived stem cells (ADSCs) on skin radiation damagies in rats. METHODS: Twelve SPF-grade Sprague Dawley rats [body weight (220±10) g] were subjected to a single dose of 10 Gy X-ray irradiation on a 1.5 cm×1.5 cm area of their dorsal skin, with a dose rate of 200 cGy/min to make skin radiation damage model. After successful modelling, the rats were randomly divided into 4 groups ( n=3), and on day 2, the corresponding cells were injected subcutaneously into the irradiated wounds: group A received 0.1 mL of rat ADSCs (1×10 ⁷cells/mL), group B received 0.1 mL of rat ADSCs (1×10 ⁷cells/mL)+1 μmol/L ICA (0.1 mL), group C received 0.1 mL of rat ADSCs (1×10 ⁷cells/mL) pretreated with a hypoxia-inducible factor 2α (HIF-2α) inhibitor+1 μmol/L ICA (0.1 mL), and group D received 0.1 mL of rat ADSCs (1×10 ⁷cells/mL) pretreated with a Notch1 inhibitor+1 μmol/L ICA (0.1 mL). All treatments were administered as single doses. The skin injury in the irradiated areas of the rats was observed continuously from day 1 to day 7 after modelling. On day 28, the rats were sacrificed, and skin tissues from the irradiated areas were harvested for histological examination (HE staining and Masson staining) to assess the repair status and for quantitative collagen content detection. Immunohistochemical staining was performed to detect CD31 expression, while Western blot and real-time fluorescence quantitative PCR (qRT-PCR) were used to measure the protein and mRNA relative expression levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor BB (PDGF-BB), fibroblast growth factor 2 (FGF-2), interleukin 10 (IL-10), transforming growth factor β (TGF-β), HIF-2α, and Notch1, 2, and 3. RESULTS: All groups exhibited skin ulcers and redness after irradiation. On day 3, exudation of tissue fluid was observed in all groups. On day 7, group B showed significantly smaller skin injury areas compared to the other 3 groups. On day 28, histological examination revealed that the epidermis was thickened and the dermal fibers were slightly disordered with occasional inflammatory cell aggregation in group A. In group B, the epidermis appeared more normal, the dermal fibers were more orderly, and there was an increase in new blood vessels without significant inflammatory cell aggregation. In contrast, groups C and D showed significantly increased epidermal thickness, disordered and disrupted dermal fibers. Group B had higher collagen fiber content than the other 3 groups, and group D had lower content than group A, with significant differences ( P<0.05). Immunohistochemical staining showed that group B had significantly higher CD31 expression than the other 3 groups, while groups C and D had lower expression than group A, with significant differences ( P<0.05). Western blot and qRT-PCR results indicated that group B had significantly higher relative expression levels of VEGF, PDGF-BB, FGF-2, IL-10, TGF-β, HIF-2α, and Notch1, 2, and 3 proteins and mRNAs compared to the other 3 groups ( P<0.05). CONCLUSION ICA may enhance the reparative effects of ADSCs on rat skin radiation damage by promoting angiogenesis and reducing inflammatory responses through the HIF-2α-VEGF-Notch signaling pathway.
Animals ; Rats, Sprague-Dawley ; Skin/pathology* ; Rats ; Vascular Endothelial Growth Factor A/genetics* ; Basic Helix-Loop-Helix Transcription Factors/genetics* ; Signal Transduction ; Flavonoids/pharmacology* ; Adipose Tissue/cytology* ; Stem Cells/cytology* ; Receptors, Notch/metabolism* ; Radiation Injuries, Experimental/metabolism* ; Wound Healing/drug effects* ; Male

OBJECTIVE: To review the nomenclature, functional unit construction, technical essentials, and prevention and treatment of complications of functional perforator flaps, so as to provide references for the structural and functional reconstruction of composite tissue defects. METHODS: By retrieving and analyzing domestic and foreign literature on anatomical research, technical innovation and clinical application of functional design and application of perforator flaps, combined with the clinical practice of our team, the methods for harvesting and integrating functional units of perforator flaps were summarized. RESULTS: Functional perforator flap refers to a perforator flap that, on the basis of perforator blood supply, carries one or more tissue functional units (such as muscles, nerves, lymphatic vessels, lymph nodes, bones, mucous membranes, joints or articular cartilages, etc.) with sufficient blood supply located in the supra-fascia and/or sub-fascia, and is used to reconstruct one or more functions of the recipient site. The design and transfer of functional perforator flaps should not only meet the needs of precise coverage of the wound, but also reconstruct the functions of the recipient site such as muscle contraction, flap sensation, lymphatic drainage, blood flow bridging, bone growth, glandular secretion or joint movement, while avoiding iatrogenic dysfunction in the donor site. CONCLUSION Functional perforator flaps have broken through the limitation of "wound coverage" and realize the integrated reconstruction of "structure-function-aesthetics".
Humans ; Perforator Flap/blood supply* ; Plastic Surgery Procedures/methods* ; Soft Tissue Injuries/surgery* ; Tissue and Organ Harvesting/methods* ; Skin Transplantation/methods*