OBJECTIVE: To review the recent advances in the application of exosome-hydrogel system for wound healing. METHODS: A wide range of recent domestic and international studies were reviewed to systematically outline the roles and mechanisms of exosomes, hydrogels, and their composite system in promoting wound repair. RESULTS: Wound healing is a complex and finely regulated process. Traditional therapies lack targeted regulation of key mechanisms such as inflammation control, angiogenesis, collagen remodeling, and re-epithelialization. The exosome-hydrogel system enhances wound repair through targeted modulation of these mechanisms and provides effective protection against bacterial infection, hypoxia, excessive oxidative stress, and hyperglycemic microenvironments. CONCLUSION The exosome-hydrogel system represents an emerging approach for chronic wound repair and skin regeneration, potentially overcoming the inherent limitations of traditional therapies. Nevertheless, the lack of standardized preparation methods and dosing protocols calls for further optimization.
Wound Healing ; Humans ; Hydrogels ; Exosomes ; Skin/injuries* ; Animals ; Re-Epithelialization

Epidermal stem cells play an pivotal role in skin self-renewal, wound repair, and re-epithelialization process. The emergence of new technologies and concepts such as single-cell sequencing and gene knockout further revealed a new mechanism of epidermal stem cells in epidermal self-renewal and wound repair, providing new ideas for wound repair. In this review, the mechanisms of proliferation, differentiation, and migration of epidermal stem cells are discussed. Combined with the analysis of researches on stem cell heterogeneity and cell plasticity, the physiological function of epidermal stem cells can be further understood. The application advances of epidermal stem cells in wound repair is also summarized, which would provide some advice for workers engaged in clinical and basic research on wound repair.
Epidermal Cells/physiology* ; Epidermis ; Humans ; Re-Epithelialization ; Skin ; Soft Tissue Injuries ; Stem Cells

Re-epithelialization is one of the core links that determines the healing process of skin wounds. The proliferation and differentiation of epidermal stem cells to form new epidermal tissue is the histological basis of re-epithelialization, and the smooth progress of the cell differentiation process of epidermal stem cells-precursor cells-terminal cells is the cytological basis for the continuous formation of new epidermal tissue. The proliferation of stem cells and their differentiation into precursor cells are the determinants of the proliferative potential of newly formed epidermal tissue, while the expansion and differentiation of precursor cells into terminal cells are key factors determining the rate of new epidermal tissue formation. The tissue microenvironment plays a key regulatory role in the process of wound re-epithelialization, and cell growth factor and inflammatory mediators are the two main components of tissue microenvironment, which play regulatory role in different aspects of proliferation and differentiation of epidermal stem cells, jointly promoting the smooth progress of wound re-epithelialization As an important part of skin immune system, the subsets of gamma-delta (γδ) T cells play crucial role in dynamically shaping early wound microenvironment via secreting different cell growth factors and inflammatory factors. From the prospective of immune microenvironment of wound, this paper discusses the role of skin γδ T cells in maintaining the balance of stem cell proliferation and differentiation and regulating wound re-epithelialization, providing a new direction for the prevention and treatment of refractory wound.
Prospective Studies ; Re-Epithelialization ; Skin ; T-Lymphocyte Subsets ; T-Lymphocytes

BACKGROUND: Split-thickness skin grafts (STSGs) are commonly used in the reconstruction of skin defects induced by trauma or burns. Although STSGs are used to successfully treat various wound types, donor site wounds can be challenging, and complications often develop. Therefore, optimal donor site dressings are required. In this study, we introduce an evidence base for patterns in how the discharge amount decreases over time, with the goal of providing insights into the selection of dressing materials. METHODS: Twenty patients with burns who received STSGs harvested from the thigh between January 2016 to April 2017 were prospectively reviewed. A donor site dressing with foam was changed daily. The weight of the foam dressing was measured before and after placement on the donor site. The wound area was calculated using Visi-Trak. The mean weight of the discharge amount per unit area (g/10 cm2) was calculated. RESULTS: The mean weight of the discharge amount per unit area (g/10 cm2) decreased from 3.84 to 2.02 (P < 0.05) and 1.09 (P < 0.05) on postoperative days 5 and 10, respectively. It further decreased to 0.61 by postoperative day 14. CONCLUSIONS: To prevent infections induced by donor site leakage, the use of highly-absorptive foam materials until 5 days after the operation is beneficial. Moreover, hydrocolloid or highly-absorptive foam materials can be used to promote re-epithelialization of the donor site after 5 days postoperatively. For re-epithelialization and wound protection, it is effective to use hydrocolloid materials starting on postoperative day 10.
Bandages ; Burns ; Colloids ; Exudates and Transudates ; Humans ; Prospective Studies ; Re-Epithelialization ; Skin Transplantation ; Skin ; Thigh ; Tissue Donors ; Transplants ; Wounds and Injuries

PURPOSE: Pain management in burn treatment is important in improving wound healing and quality of life. Ibuprofen is a proven pain relieving agent in patients with partial thickness burn by intraveous injection. The purpose of this study is to evaluate the efficacy of Biatain Ibu® (polyurethane foam containing ibuprofen) in pain control for outpatients with partial thickness burns. METHODS: A prospective randomized clinical trial was performed in outpatients with partial thickness burn from August 1, 2017 to July 31, 2018. Acute pain, chronic pain, complications, days for re-epithelialization and patient's satisfaction were compared between Biatain Ibu® and Biatain® groups. RESULTS: A total of 20 patients (Biatain Ibu®, n=10; Biatain®, n=10) were assessed in the trial. On Burn days 3, 5, 7, 11, 13, and 15, the acute pain levels were significantly lower in the Biatain Ibu® group than in the Biatain® group. Complications, chronic pain levels and days for re-epithelialization were not significantly different between the two groups. Patient's satisfaction was not statistically significant but was higher in the Biatain Ibu® group. CONCLUSION: Biatain Ibu® is effective in relieving pain in outpatients with partial thickness burn without decreasing patient satisfaction, wound healing ability or developing any complications.
Acute Pain ; Bandages ; Burns ; Chronic Pain ; Humans ; Ibuprofen ; Outpatients ; Pain Management ; Patient Satisfaction ; Prospective Studies ; Quality of Life ; Re-Epithelialization ; Wound Healing ; Wounds and Injuries

PURPOSE: The purpose of this study was to evaluate the efficacy of Betafoam in terms of wound healing and safety. METHODS: Fifty-four male adult Sprague-Dawley rats (weight, 200–250 g) were used in the study. Full-thickness skin defects were created on the back of each rats. The rats were assigned to 6 groups according to the type of wound dressing used (n = 9 for each group): Betafoam, Allevyn-Ag, Mepilex-Ag, Medifoam silver, Polymem-Ag, and gauze. The wound size, histological findings, and amount of DNA on the changed dressings for each group were analyzed and compared. RESULTS: All groups showed an effective decrease in wound size. However, the differences between Betafoam and the other dressings were statistically significant on day 14 (P < 0.05). The number of newly generated blood vessels in the Betafoam group was significantly higher than in the gauze, Allevyn-Ag, and Medifoam silver groups (P < 0.001). In the Betafoam group, the proportion of collagen deposition was highest and showed a significantly superior arrangement of collagen fibers compared with the gauze, Allevyn-Ag, Mepilex-Ag, and Medifoam silver groups. The total content of the remaining DNA counts of the exchanged dressings were significantly lower in the Betafoam group than the others. CONCLUSION: Betafoam is effective in wound healing and provides the best performance amongst the various types of dressing materials in terms of re-epithelialization, angiogenesis, collagen deposition, and tissue invasion.
Adult ; Animals ; Bandages ; Blood Vessels ; Collagen ; DNA ; Humans ; Male ; Polyurethanes ; Povidone-Iodine ; Rats ; Rats, Sprague-Dawley ; Re-Epithelialization ; Silver ; Skin ; Wound Healing ; Wounds and Injuries

PURPOSE: Numerous indices have been proposed to analyse wound healing in oral soft tissues, but each has specific shortcomings. A new method of analysis, the Early Wound Healing Score (EHS), was evaluated in the present study. The aim was to assess more accurately early healing by primary intention of surgical incisions in periodontal soft tissues. METHODS: Twenty-one patients were treated with different surgical procedures comprising 1 or 2 vertical releasing incisions as part of a surgical access flap. Twenty-four hours after surgery, early wound healing at the vertical releasing incisions was assessed using the EHS. This score assessed clinical signs of re-epithelialization (CSR), clinical signs of haemostasis (CSH), and clinical signs of inflammation (CSI). Since complete wound epithelialization was the main outcome, the CSR score was weighted to be 60% of the total final score. Accordingly, a score of 0, 3, or 6 points was possible for the assessment of CSR, whereas scores of 0, 1, or 2 points were possible for CSH and CSI. Higher values indicated better healing. Accordingly, the score for ideal early wound healing was 10. RESULTS: Thirty vertical releasing incisions were assessed in 21 patients. At 24 hours after incision, 16 vertical releasing incisions (53.33%) received the maximum score of CSR, while 6 cases (20%) received an EHS of 10. None of the cases received 0 points. CONCLUSION: The EHS system may be a useful tool for assessing early wound healing in periodontal soft tissue by primary intention after surgery.
Gingiva ; Humans ; Inflammation ; Intention ; Methods ; Periodontal Diseases ; Re-Epithelialization ; Soft Tissue Injuries ; Symptom Assessment ; Wound Healing ; Wounds and Injuries

PURPOSE: Aim of this study was to assess the safety and effectiveness of Keraheal-Allo® (Biosolution Co., Ltd., Korea) in patients with deep second-degree burn as a part of post marketing surveillance. METHODS: Seventy-five patients with deep second-degree burn were enrolled from April 2017 to October 2017. Keraheal-Allo, a thermos-sensitive hydrogel-type allogeneic keratinocytes, was applied to 90 deep second-degree burn sites of 75 patients. After application of Keraheal-Allo, the efficacy was assessed as the period of 100% re-epithelialization that was evaluated every time dressing was changed. RESULTS: The mean re-epithelialization period in the treated sites with KeraHeal-allo was 13.67±5.11 days. There was no severe adverse event. CONCLUSION: In conclusion, this thermo-sensitive hydrogel-type allogeneic keratinocytes have the clinical usefulness in terms of the safety, efficacy and ease of use.
Bandages ; Burns* ; Humans ; Keratinocytes* ; Marketing ; Re-Epithelialization

Acute kidney injury is a clinical syndrome that can be caused by numerous diseases including acute tubular necrosis (ATN). ATN evolves in several phases, all of which are accompanied by different immune mechanisms as an integral component of the disease process. In the early injury phase, regulated necrosis, damage-associated molecular patterns, danger sensing, and neutrophil-driven sterile inflammation enhance each other and contribute to the crescendo of necroinflammation and tissue injury. In the late injury phase, renal dysfunction becomes clinically apparent, and M1 macrophage-driven sterile inflammation contributes to ongoing necroinflammation and renal dysfunction. In the recovery phase, M2-macrophages and anti-inflammatory mediators counteract the inflammatory process, and compensatory remnant nephron and cell hypertrophy promote an early functional recovery of renal function, while some tubules are still badly injured and necrotic material is removed by phagocytes. The resolution of inflammation is required to promote the intrinsic regenerative capacity of tubules to replace at least some of the necrotic cells. Several immune mechanisms support this wound-healing-like re-epithelialization process. Similar to wound healing, this response is associated with mesenchymal healing, with a profound immune cell contribution in terms of collagen production and secretion of profibrotic mediators. These and numerous other factors determine whether, in the chronic phase, persistent loss of nephrons and hyperfunction of remnant nephrons will result in stable renal function or progress to decline of renal function such as progressive chronic kidney disease.
Acute Kidney Injury ; Collagen ; Extracellular Traps ; Hypertrophy ; Inflammation ; Necrosis* ; Nephrons ; Phagocytes ; Re-Epithelialization ; Renal Insufficiency, Chronic ; Wound Healing

BACKGROUND: Chronic wounds occur due to failure of the normal healing process, associated with a lack of deposition of cellular components and a suitable microenvironment such as the extracellular matrix (ECM). Acellular dermal matrix (ADM) is viewed as an ECM substitute, and a paste-type ADM has recently been introduced. We hypothesized that CGPaste, an injectable paste-type ADM, could serve as a scaffold and promote wound healing. METHODS: We retrospectively studied seven patients in whom CGPaste was applied between 2017 and 2018, who had pressure ulcers, necrotizing fasciitis, diabetic foot ulcers, traumatic defects, and osteomyelitis. The goal of applying CGPaste was to achieve complete wound healing with re-epithelialization or growth of granulation tissue, depending upon the wound bed status. CGPaste was injected based on the wound size along with the application of a dressing. RESULTS: Four of the seven patients showed granulation tissue on their wound bed, while the other three patients had a bony wound bed. The mean wound area was 453.57 mm2 and the depth was 10.71 mm. Wound healing occurred in five of the seven patients (71.43%). The mean duration of complete healing was 2.4 weeks. Two patients showed failure due to paste absorption (29.57%); these patients had wound beds comprising bone with relatively large and deep wounds (40×30 and 30×20 mm2 in area and 15 and 10 mm in depth). CONCLUSIONS: CGPaste is an effective option for coverage of small and deep chronic wounds for which a flap operation or skin grafting is unfeasible.
Absorption ; Acellular Dermis* ; Bandages ; Diabetic Foot ; Extracellular Matrix ; Fasciitis, Necrotizing ; Granulation Tissue ; Humans ; Osteomyelitis ; Pressure Ulcer ; Re-Epithelialization ; Retrospective Studies ; Skin Transplantation ; Ulcer* ; Wound Healing ; Wounds and Injuries*