RARE DISEASE
Partial deep dermal and full thickness burns
Partial deep dermal and full thickness burns
Partial deep dermal and full thickness burns
Drug discovery
19
drugs
With orphan designations
Overview
Partial deep dermal (deep second-degree) and full-thickness burns involve significant destruction of skin layers, extending into the reticular dermis or deeper tissues (subcutaneous fat, muscle, or bone) [1][2][6]. Partial deep dermal burns appear mottled pink/white with minimal blanching and reduced sensation, while full-thickness burns are leathery, insensate, and often charred [1][6][15]. These burns lack sufficient regenerative capacity for spontaneous healing, typically requiring surgical intervention [3][8][12].
Therapies
Deep dermal: Initial conservative management with silver-based dressings (e.g., Acticoat) or enzymatic debridement (NexoBrid®) [3][16], transitioning to tangential excision/grafting if unhealed by 3 weeks [8][12].
Full-thickness: Early excision (within 3–5 days) and autografting; temporizing measures include allografts or synthetic substitutes (Integra®) [12][16].
Categories: rare skin diseases
Research Papers
967 drug discovery papers about Partial deep dermal and full thickness burns, with 1 first-in-class and 14 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
967 drug discovery papers about Partial deep dermal and full thickness burns, with 1 first-in-class and 14 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
proteins
2026-07-29 | Bromelain-based enzymatic debridement versus standard of care in deep partial- and full-thickness burns: A systematic review and meta-analysis of randomized controlled trials.
Management of debridement-eligible thermal burns requires accurate removal of devitalized tissue. Tangential excision remains limited by imprecise depth assessment beneath opaque eschar, risking unintended dermal sacrifice. Bromelain-based enzymatic debridement (BBD) has emerged as an alternative; however, its impact on patient-level surgical outcomes has not been rigorously quantified in randomized trials. A systematic review and meta-analysis of randomized trials compared BBD with standard of care (SOC) in acute deep thermal burns. The primary outcome was the proportion requiring surgical excision. Random-effects models pooled effects. A prespecified sensitivity analysis evaluated a wound-level trial. Risk of bias was assessed using the Cochrane RoB 2 tool. Five randomized trials met criteria. Four reporting per-patient outcomes contributed to the primary meta-analysis (n = 336). BBD reduced surgical excision versus SOC (RR, 0.11; 95% CI, 0.06-0.23; I² = 0%), corresponding to an absolute risk reduction of 65% and a number needed to treat of 1.5. BBD was also associated with reduced autograft use, shorter time to debridement, and comparable or improved blinded scar assessments at 12 months. Open-label design was the principal source of potential bias. Sensitivity analysis including the wound-level trial preserved effect direction with increased heterogeneity. Randomized evidence demonstrates that, in early-treated debridement-eligible burns with limited total body surface area burned (TBSA), BBD reduces operative and graft burden without compromising wound closure or long-term remodeling. Future trials incorporating blinded operative endpoint adjudication, objective assessment of dermal preservation and broader clinical outcomes will further clarify treatment effect and optimize patient selection.
2026-03-27 | Histopathological Changes Following Bromelain-Based Enzymatic Debridement (NexoBrid®): A Comprehensive Systematic Review of Preclinical and Clinical Evidence.
Background: NexoBrid® (NXB; MediWound Ltd., Yavne, Israel) (anacaulase-bcdb) is a bromelain-based enzymatic debriding agent approved for eschar removal in burn care. Despite widespread clinical use, histological evidence of tissue-level changes after enzymatic debridement remains limited. This systematic review aimed to evaluate preclinical and clinical studies describing histological findings following bromelain-based enzymatic debridement of thermal burns. Methods: Following PRISMA 2020 guidelines, we performed parallel systematic searches of preclinical (animal) and clinical (human) studies across PubMed, Embase, CENTRAL, Web of Science, and Scopus. Included studies reported thermal burns treated with bromelain-based enzymatic debridement and tissue biopsies with histological analysis. Quality was assessed using the SYRCLE Risk of Bias Tool (preclinical) and JBI Critical Appraisal Checklists (clinical). Results: Six preclinical studies (five porcine, one rat) met inclusion criteria. Findings included: selective eschar removal with dermal preservation; protection of the zone of stasis (67% partial- vs. 100% full-thickness necrosis; p = 0.05); viable dermal thickness of 1.1 ± 0.7 mm; and accelerated re-epithelialization (7.4 ± 0.8 vs. 9.1 ± 2.1 days; p < 0.05). Only two clinical studies (n = 9 patients) met the inclusion criteria: one case series (n = 8) and one case report. Clinical findings showed upper dermal homogenisation with preserved deep dermis, vascular congestion correlating with pinpoint bleeding, and pseudoeschar formation via transepidermal elimination. Conclusions: Preclinical evidence supports selective enzymatic debridement with dermal preservation. However, clinical histological data are limited to nine patients after over 13 years of use. This highlights a critical translational gap and underscores the need for prospective clinical histological studies.
2026-03-01 | 1011. Case Study. Bovine Collagen Dermal Matrix Facilitates Re-epithelialization in Mixed Partial-thickness Burn Wounds: A Case Series
Abstract Patient Presentation (age range, injury details, relevant history) This case series describes two male patients aged 61 and 75 years, with multiple comorbidities and mixed partial-thickness thermal burns measuring approximately 100 cm2 and 300 cm2 on the left forearm and right lower extremity, respectively. Clinical Challenges In burn and wound management, cutting-edge interventional studies and emerging technologies are most often applied to full-thickness and deep partial thickness injuries requiring surgical closure. In contrast, superficial and mixed partial-thickness wounds are typically managed more conservatively and receive less attention in interventional literature. This relative gap in evidence-based innovation may affect therapeutic options and delay healing for patients who fall into such category. By exploring new technologies such as bovine collagen based dermal matrix (BCDM), there is an opportunity to expand treatment paradigms for these patients. To illustrate the potential role of this approach, we present these two patients with mixed partial-thickness burns successfully treated with a novel BCDM. Management Approach After initial wound care and debridement using a combination of sharp excision and hydrotherapy, a bovine collagen–based dermal matrix (BCDM) was applied at bedside directly to the wounds. Post-application wound management consisted of a primary non-adherent dressing layer, followed by compressive layers (Patient 1) or negative pressure wound therapy (NPWT) (Patient 2). Dressings for both were removed at 7 days post-application and were subsequently switched to antimicrobial ointment, non-adherent contact layer and compressive outer dressings. Both patients were monitored weekly for re-epithelialization, complications, and overall wound healing. Outcomes Patient 1 achieved complete re-epithelialization within 4 weeks without complications or the need for autografting. Patient 2 was ready for autograft at first dressing change, however he was lost to follow up until he returned at 4 weeks with a fully healed wound. Post-application wound care was straightforward, and both patients reported satisfaction with cosmetic and functional outcomes, particularly with the avoidance of operative intervention. Lessons Learned This case series demonstrates that BCDM can be an effective treatment option for mixed partial thickness burns, promoting timely healing while minimizing patient morbidity and possibly eliminating the need for grafting. These early findings suggest that collagen-based dermal matrices may expand the role of advanced biologics beyond full-thickness injuries, offering a valuable alternative in the management of selected partial-thickness burns. Applicability to Practice The use of BCDM in outpatient or bedside settings may reduce the need for operative procedure and improve patient-centered outcomes in partial thickness burn management.
2026-03-01 | 830. A Bovine Dermal Collagen Matrix for Deep Partial-thickness Burns: A Case Series
Abstract Introduction Dermal matrices have become an integral part of modern burn care due to their ability to reduce pain, enhance cosmesis, and restore function in full-thickness wounds. In the context of deep partial-thickness wounds, dermal matrices can serve as an advanced dressing option to support re-epithelialization, potentially eliminating the need for traditional autografting. A bovine dermal collagen matrix (BDCM) comprised of crosslinked, type I and type III collagen has demonstrated effectiveness in supporting rapid cellular infiltration and vascular tissue formation in porcine full-thickness wounds preclinically as well as facilitating early autograft readiness in two recent clinical cases. Building on its utility in full-thickness wounds, our institution was the first to evaluate the clinical efficacy of BDCM as an advanced dressing in deep partial-thickness burns. Methods A retrospective chart review was conducted from March to May 2025 to evaluate the safety and effectiveness of BDCM in 3 patients with deep partial-thickness burns. Outcomes assessed included matrix integration, time to re-epithelialization, extent of repigmentation in treated areas, and pain assessment. Results In case 1, an 18-year-old male with a 3% total body surface area (TBSA) deep partial-thickness grease burn to the right lower leg, ankle, and foot was treated with BDCM in combination with a skin cell suspension autograft (SCSA). He was discharged on post-operative day (POD) 1 with full ambulation and a night splint. On POD 6, the BDCM had fully integrated, with epidermal budding and minimal open areas; the patient reported no pain. On POD 13, 100% re-epithelialization was noted, and melanin pigment had begun to return. In case 2, a 51-year-old male had a 0.5% TBSA deep partial-thickness chemical burn to bilateral hands and wrists. On POD 7, the BDCM had fully integrated with one small open area on the fifth digit. Complete (100%) re-epithelialization was achieved by POD 20. In case 3, a 33-year-old male with an 8% TBSA deep partial-thickness scald burn to bilateral lower extremities was treated with BDCM and SCSA. On POD 8, the BDCM had mostly incorporated with 95% re-epithelialization. By POD 15, early repigmentation was noted. Conclusions These cases demonstrate the safety and efficacy of the BDCM in supporting healing of deep partial-thickness burns. Importantly, the BDCM supported re-epithelialization and repigmentation, thus offering a more diverse treatment option within burn care for deep partial-thickness injuries. Additionally, patients experienced reduced pain post-application and simplified aftercare, further highlighting the clinical utility of the BDCM. Applicability of Research to Practice BDCM is a safe and viable advanced dressing option for healing deep partial-thickness burns. Funding for the study N/A.
2025-12-23 | Burn Classification, Total Body Surface Area Assessment, And Epidemiology: Foundations For Modern Burn Care
characterized by tissue destruction, systemic inflammatory response, metabolic derangements, and potential multiorgan dysfunction. Despite advances in prevention and treatment, burns continue to pose a significant global health burden. Early and accurate assessment of burn depth and extent remains the cornerstone of effective management, directly influencing triage decisions, fluid resuscitation strategies, need for surgical intervention, and referral to specialized burn centers. This article reviews burn classification by depth, methodologies for estimating total body surface area (TBSA), global epidemiological patterns, and the clinical relevance of accurate initial burn evaluation in contemporary practice. Classification of Burns by Depth Burn depth reflects the degree of tissue destruction and the regenerative capacity of the skin, making it one of the strongest predictors of healing time, infection risk, scarring, and functional outcome. Superficial (First-Degree) Burns are limited to the epidermis. Clinically, they present with erythema, tenderness, and dry skin without blistering. Capillary refill is preserved, and pain is prominent due to intact nerve endings. These burns heal within days through epidermal regeneration and do not result in scarring. Superficial Partial-Thickness (Second-Degree) Burns involve the epidermis and superficial dermis. They are characterized by blister formation, moist appearance, severe pain, and brisk capillary refill. Because epithelial appendages such as hair follicles and sweat glands remain intact, spontaneous re-epithelialization occurs rapidly, usually within two to three weeks, with minimal scarring. Deep Partial-Thickness (Second-Degree) Burns extend deeper into the dermis, damaging a greater proportion of dermal structures. These burns often appear mottled, pale, or erythematous, with diminished sensation and sluggish capillary refill. Healing is prolonged and unpredictable, frequently exceeding three weeks, which increases the risk of hypertrophic scarring and contractures. Surgical excision and grafting are commonly required. Full-Thickness (Third-Degree) Burns involve complete destruction of the epidermis and dermis. The affected tissue appears dry, leathery, and insensate due to nerve destruction. Because no epithelial elements remain, spontaneous healing is not possible, and definitive management requires early excision and skin grafting to reduce infection risk and improve outcomes. Fourth-Degree Burns extend beyond the skin into underlying fascia, muscle, tendon, or bone. These devastating injuries are often associated with high-energy mechanisms and severe systemic insult. Management is complex and may necessitate limb amputation, staged reconstruction, or palliative approaches depending on patient condition and associated injuries.1
small molecules
2026-03-10 | Evaluation of Burn Depth using Indocyanine Green: Discrepancies Between Macroscopic Visualization and the Microenvironment.
Burn wound management is guided by the depth of dermal tissue damage. Standard practice for this depth assessment is daily visual evaluation of the wound by an experienced burn surgeon, which is inherently subjective and at times inaccurate. Perioperative fluorescence imaging with indocyanine green (ICG) has emerged as a potential tool to objectively evaluate burn depth. The current study aims to explore the relationship between ICG angiography (ICGA), Second-window ICG (SWIG), and burn depth, with the goal of understanding how this technology could guide the prognosis and treatment of human burn wounds. Patients (n = 14) with indeterminate depth or deep partial thickness burns received an infusion of ICG on post-burn day 2-3 or the day before surgery. Imaging was performed immediately after injection for angiography as well as the following day for SWIG. A full-thickness tissue biopsy was obtained for histologic evaluation. In vitro primary human fibroblasts and keratinocytes were cultured, subjected to heat injury (65 deg C for 2.5 or 5 minutes), and incubated with ICG. Flow cytometry was used to classify the cells as live, apoptotic, or necrotic based and to quantify ICG uptake. ICGA perfusion parameters are increased in burn wounds that did not require grafting and ICGA egress slope correlates to SWIG fluorescence intensity. Furthermore, SWIG microscopic fluorescence intensity correlates to histologic burn depth and colocalizes in necrotic region of burn injury, however there is high interpatient variability between SWIG fluorescence intensity and histologic burn depth, predicted healing potential, and graft status. Flow cytometric analysis of in vitro skin cells shows that preferential ICG binding to necrotic cells contributes to SWIG signal in a burn, with binding influenced by cell type and injury severity. Overall, this study suggests that fluorescence imaging has the potential to aid in the assessment of healing potential, although current challenges related to imaging variability, interpretation, and clinical integration must be addressed to optimize its utility in burn management.Clinical trials number: NCT05593523.
2024-03-14 | Natural Compounds and Biomimetic Engineering to Influence Fibroblast Behavior in Wound Healing
Throughout history, natural products have played a significant role in wound healing. Fibroblasts, acting as primary cellular mediators in skin wound healing, exhibit behavioral responses to natural compounds that can enhance the wound healing process. Identifying bioactive natural compounds and understanding their impact on fibroblast behavior offers crucial translational opportunities in the realm of wound healing. Modern scientific techniques have enabled a detailed understanding of how naturally derived compounds modulate wound healing by influencing fibroblast behavior. Specific compounds known for their wound healing properties have been identified. Engineered biomimetic compounds replicating the natural wound microenvironment are designed to facilitate normal healing. Advanced delivery methods operating at micro- and nano-scales have been developed to effectively deliver these novel compounds through the stratum corneum. This review provides a comprehensive summary of the efficacy of natural compounds in influencing fibroblast behavior for promoting wound regeneration and repair. Additionally, it explores biomimetic engineering, where researchers draw inspiration from nature to create materials and devices mimicking physiological cues crucial for effective wound healing. The review concludes by describing novel delivery mechanisms aimed at enhancing the bioavailability of natural compounds. Innovative future strategies involve exploring fibroblast-influencing pathways, responsive biomaterials, smart dressings with real-time monitoring, and applications of stem cells. However, translating these findings to clinical settings faces challenges such as the limited validation of biomaterials in large animal models and logistical obstacles in industrial production. The integration of ancient remedies with modern approaches holds promise for achieving effective and scar-free wound healing.
2023-12-29 | ANTIOXIDANTS SUPPLEMENTATION BASED ON NATURAL PRODUCTS IN THE TREATMENT OF THE THERMAL SKIN INJURY
Thermal injuries are a major medical, economic and social problem, whose severity, morbidity, mortality, prognosis and treatment outcome directly depend on the surface and depth of the burn, but also on the patient's age, health status and accompanying complications. The treatment of thermal injury is long and complex, and the outcome is often uncertain with a very complex rehabilitation process, because the injury damages both physical and psychological health. Constant innovations in the protocol of medical treatment and the search for new mechanisms involved in the pathogenesis of burns can be helpful in successful treatment. Therefore, there is a constant search for adjuvant therapies that will improve results like HBO, AO, platelet- rich plasma, negative pressure wound therapy and others. In recent years, the application of antioxidants as adjuvant therapy for the care and treatment of wounds has been the subject of various researche. Antioxidants are biologically active molecules that prevent the creation of free radicals in the body and at the same time neutralize the existing ones, this way participating in maintaining the oxidative status at the desired level. Antioxidant -rich natural products may provide a solution to improve wound healing. The application of antioxidant therapy has shown numerous benefits in improving the outcome of burns. However, more information is needed from the clinical trials on the use of natural products, especially in combination with other therapies. Keywords: thermal skin injury, hyperbaric oxygen therapy, antioxidant rich natural products
2023-12-27 | Temperature and pH-sensitive chitosan-collagen hydrogels for antimicrobial and wound healing applications
Hydrogels have proven to be of great value because of their useful properties and functions. Temperature and pH-sensitive chitosan-collagen-based hydrogels have drawn research interest in the area of wound care. Their unique mechanism allows them to release antimicrobial agents in response to changes in the environment and aids in efficient healing of wounds. The current review aims to describe various composite hydrogels of chitosan and collagen, their temperature and pH sensitivity, the antimicrobial effect of chitosan-collagen hydrogels and their applications in wound healing. Sources and properties of chitosan and collagen have also been stated in order to highlight their importance in these hydrogels. The main focus revolves around the potential of chitosan-collagen hydrogels as antimicrobial biomaterials for healing wounds in an efficient manner.
2023-11-07 | The Use of Carboxytherapy for the Treatment of Deep Partial-Thickness Skin Burns After Circumferential and High-Definition Liposuction: Promising Clinical Results in 5 Consecutive Cases
Abstract Background Literature on skin burn treatment after liposuction is limited. To date, no publication has discussed possible treatments for this complication despite its relatively frequent incidence. Objectives The objective of this study is to report the early experiences of the use of carboxytherapy for the treatment of Grade IIB partial-thickness skin burns after liposuction. We aim to analyze its potential beneficial effects on wound healing and skin pigmentation, without the need for additional corrective surgery or permanent scarring. Methods Five patients who showed Grade IIB skin burns within 24 h after circumferential and high-definition liposuction were treated with carboxytherapy. Wound healing was evaluated after 1 and 2 weeks. Scar formation and skin pigmentation were evaluated after 3 months. Results Carboxytherapy treatments were either performed every day or every other day for 1 or 2 weeks, depending on the wound healing. At 2 weeks postoperatively, all skin burns showed complete or near-complete healing. At 3 months, there were no zones of hypertrophic scarring or skin contracture. No complications with regard to the carboxytherapy treatment were observed. Conclusions Carboxytherapy is an easy-to-use, affordable, and safe treatment for Grade IIB skin burns postliposuction. Its known influence on neo-angiogenesis and oxygen release in a hypoxic environment has beneficial effects on wound healing and avoidance of hypertrophic scarring and skin hyperpigmentation after skin burns. It can potentially become a useful addition for surgeons who perform liposuction and body contouring. Further studies with larger numbers of patients are necessary to determine its full potential. Level of Evidence: 4
cell therapies
2026-06-22 | The Use of Kerecis Omega3 Wound Fish Skin Graft for the Treatment of Deep Burn Wounds.
Addressing deep partial-thickness burns (DPTBs) and full-thickness burns (FTBs) remains a significantly challenging task in modern burn surgery. Among a broad lineup of wound products, biological adjuncts like fish skin-derived scaffolds offer unique regenerative properties, presenting new possibilities in complex wound management. We herein report our institutional clinical experience with the fish skin-based scaffold Kerecis Omega3 Wound. This retrospective, single-center case series evaluated all patients with DPTBs and FTBs treated with Kerecis Omega3 Wound between 2020 and 2024 at the burn center of the University Hospital Zurich. The specific indications for intervention, depth of burn injury, anatomical regions of application, subsequent need for further surgery, and short- and long-term complications were systematically assessed. Twenty-seven patients were reviewed, exhibiting a mean affected total body surface area of 35.73% and an average abbreviated burn severity index score of 7.74. Fish skin was used in an acute setting in 21 cases; for the remaining cases, it was used for chronic wound-healing disturbances following burn injury. The most frequently treated anatomical region was the upper extremity. Almost 50% of the DPTB wounds healed spontaneously following treatment with Kerecis Omega3 Wound. Conversely, all FTBs required further skin grafting or other reconstructive measures. Postsurgical infections occurred in 4 patients, necessitating the removal of the product. Contractures were observed in 3 patients with FTBs during clinical follow-up. Kerecis Omega3 Wound represents a valuable adjunct for wound conditioning in patients with DPTBs, either as a preparation before skin grafting or to stimulate spontaneous wound regeneration. Regarding FTBs, its efficacy in restoring the dermal layer requires further research and clinical validation.
2026-03-01 | 1013. Case Study. Fish Skin Grafts for Partial-thickness Electrical Burns: A Mini Case Series of Successful Outcomes
Abstract Patient Presentation (age range, injury details, relevant history) A 27-year-old and 36-year-old healthy Hispanic male with Fitzpatrick type IV skin sustained 1% electrical burns to their left (non-dominant) hands during a construction accident. The 27-year-old had superficial and deep second-degree burns to dorsal digits 3-5 (including PIP and DIP joints), with near circumferential wrist involvement. The 36-year-old had superficial second-degree burns to all dorsal digits (including MCP, PIP, and DIP joints) and volar wrist involvement. Clinical Challenges Deep partial thickness burns spanning multiple joints. The goal was to reduce scarring and optimize hand function, focusing on a quick return to work, effective pain management, and brief hospitalization. Management Approach Both patients underwent 5 days of local wound care followed by tangential excision and piscine xenograft coverage. Wound care included twice daily cleansing, Silvadene application, gauze wrap, elastic compression and elevation. Occupational therapy was consulted. Tangential excision was performed with a Goulian blade, followed by the application of piscine xenografts fixed with staples. Sterile dressings included antibiotic ointment, gauze wrap, and an elastic compression bandage. Both patients were discharged with one-week follow-up for dressing changes. Outcomes A mini case series with terrific cosmetic and functional outcomes while providing prompt coverage of a raw wound, thus minimizing pain. Piscine xenograft was pursued in lieu of autograft due to the superficial partial thickness depth. The piscine dermal matrix offered the additional benefits of modulating inflammation, promoting neovascularization and reinforcing the dermal construct with natural collagen, elastin, glycosaminoglycans and extracellular membrane components resulting in a more pliable neodermis. At 1 week post-op, full graft incorporation was noted in deeper areas, while more superficial injuries exhibited partial graft loss as dry, scaly tissue. Neither patient required narcotics postoperatively. Both had some restricted grip formation, more pronounced in the younger male. They were provided wound care, hand exercises, and outpatient occupational therapy prescriptions. At 2 weeks post-op, both patients had full epithelialization, no hypertrophy, and improved range of motion. Wound care transitioned to moisturizing, and they were provided compression gloves and sun exposure precautions. They returned to work at this time without functional deficits. At 7 months post-op, both patients had excellent cosmetic outcomes and regained native functionality, with no hypertrophy or contracture. The patients' lack of co-morbidities and good nutritional status likely aided healing. Lessons Learned In appropriate cases, piscine xenografts can achieve timely wound healing with optimal tissue pliability and cosmesis without the need for autograft, thus reducing procedural time, minimizing pain, and avoiding donor site morbidity. Applicability to Practice:
2025-10-15 | Consensus Recommendations for Intact Fish Skin Graft in the Management of Burn Injury
Background: Intact fish skin graft (IFSG) derived from North Atlantic cod emerged as a treatment for burns in 2019. This consensus paper presents the best to date evidence and experience-based recommendations from eight U.S. burn care experts regarding optimal use of IFSG across different burn depths and wound types. Methods: Eight U.S. burn specialists with routine IFSG experience conducted a two cycle modified Nominal Focus Group. A systematic literature search (through April 2024) was conducted, followed by informed discussion, and the generation of consensus statements. Consensus was defined as ≥80 % agreement on a 5 point Likert scale. Results: Full or strong consensus (≥80 %) was reached on 12/15 statements. IFSG is recommended for: mid-dermal & deep-dermal partial-thickness burns (as definitive treatment), full thickness traumatic & burn wounds (in a 2-stage procedure before split-thickness skin graft). IFSG is not routinely recommended for purely epidermal burns. Based on recommendations from panelists, IFSG should be applied immediately after thorough debridement except in traumatic wounds when IFSG application should be delayed until clear demarcation and resolution of any infection. Reapplication is rarely required and, if needed, should occur 6–10 days after the initial graft. For wounds >100 cm², negative pressure wound therapy (NPWT) is the preferred bolster. The panel agreed IFSG accelerates readiness for STSG, decreases procedural pain, and can reduce nursing burden and overall cost of care. Recommendations: Clinicians should reserve IFSG for deep-dermal or full thickness burns and traumatic wounds and should pair IFSG with NPWT for large areas. IFSG is not needed in superficial burns that heal adequately with standard care. Prospective trials in deep-dermal partial thickness and full thickness burns remain a priority.
2024-11-13 | Management of Large Full-Thickness Burns Using Kerecis™ Acellular Fish Skin Graft and ReCell™ Autologous Skin Cell Suspension: A Case Report of Two Patients with Large Surface Area Burns.
Novel treatments for extensive full-thickness burns revolve around fluid control, addressing systemic inflammatory derangements, and achieving early skin coverage with acceptable cosmetic and functional results. Recent advances in the management of extensive burns include fish skin xenografts, such as Kerecis Omega-3 acellular dermal substitute. Reported to be non-allergenic and antimicrobial, this Atlantic Cod skin derivative has the potential to supplement the management of patients with large surface area burns. A chart review was performed on two complex patients. Patient 1 suffered 65% partial and full-thickness burns after lighting herself on fire with gasoline, and patient 2 suffered 86% partial and full-thickness burns following a methamphetamine explosion. The patients were both treated with a multi-step process using cadaveric allografts, Kerecis acellular fish skin placement, and autologous split-thickness skin grafts (STSG). Case 2 utilized ReCell autologous skin cell suspension and Novosorb bilaminate dermal substitute (BTMTM) due to limited donor sites. Complete coverage and epithelization were achieved on both patients but required multiple reapplications of autograft and Kerecis. Contractures of the neck, elbows, and hand were present in Case 1. Kerecis xenografting may have an expanding role in burn management due to standalone capabilities for deep partial-thickness burns and ease of use. Further evaluation is needed to establish the most optimal timing of use and best zones of application to improve take and reduce contractures.
2024-04-17 | 810 Development of a Porcine Burn Wound Model
Abstract Introduction Deep partial thickness burns generally require more than 2-3 weeks to heal often resulting in hypertrophic scarring and patient morbidity. Because the skin of pigs most closely resembles that of humans, the pig is often used as an experimental burn wound model. We describe the development of a reproducible burn wound model in Yorkshire pigs. Methods We created standardized 5 x 5 cm burns on the backs and flanks of anesthetized domestic pigs (30 kg) using a radiant heating device set at 600 degrees C and applied to the animal’s skin for 5, 10, or 15 seconds. Full thickness 4 mm punch biopsies were obtained from the burns at 4 and 24 hours for burn depth evaluation. The tissue sections were stained with Hematoxylin and Eosin, HMGB-1 (a marker of necrosis) and activated cleaved caspase 3 (a marker of apoptosis). The tissue sections were viewed by a board-certified dermatopathologist blinded to duration of exposure. The primary outcome was the deepest level of injury to the blood vessels or epithelial appendices (hair follicles or apocrine glands). Results Exposure of the pigs’ skin to the heating device for periods of 5, 10, and 15 seconds resulted in superficial partial, deep partial and full thickness burns respectively. Average depth of dermal injury 24 hours after exposure was 0.4 mm, 1.3 mm, and 2.4 mm for exposure times of 5, 10 and 15 seconds respectively. Conclusions We describe a standardized porcine model for creating reproducible superficial partial, deep partial and full thickness burns. Applicability of Research to Practice This model is now being used to investigate novel therapies for deep burns.
antibodies
2023-10-07 | Kinetics of Inflammatory Mediators in the Immune Response to Burn Injury: Systematic Review and Meta-Analysis of Animal Studies
Burns are often accompanied by a dysfunctional immune response, which can lead to systemic inflammation, shock, and excessive scarring. The objective of this study was to provide insight into inflammatory pathways associated with burn-related complications. Because detailed information on the various inflammatory mediators is scattered over individual studies, we systematically reviewed animal experimental data for all reported inflammatory mediators. Meta-analyses of 352 studies revealed a strong increase in cytokines, chemokines, and growth factors, particularly 19 mediators in blood and 12 in burn tissue. Temporal kinetics showed long-lasting surges of proinflammatory cytokines in blood and burn tissue. Significant time-dependent effects were seen for IL-1β, IL-6, TGF-β1, and CCL2. The response of anti-inflammatory mediators was limited. Burn technique had a profound impact on systemic response levels. Large burn size and scalds further increased systemic, but not local inflammation. Animal characteristics greatly affected inflammation, for example, IL-1β, IL-6, and TNF-α levels were highest in young, male rats. Time-dependent effects and dissimilarities in response demonstrate the importance of appropriate study design. Collectively, this review presents a general overview of the burn-induced immune response exposing inflammatory pathways that could be targeted through immunotherapy for burn patients and provides guidance for experimental set-ups to advance burn research. Burns are often accompanied by a dysfunctional immune response, which can lead to systemic inflammation, shock, and excessive scarring. The objective of this study was to provide insight into inflammatory pathways associated with burn-related complications. Because detailed information on the various inflammatory mediators is scattered over individual studies, we systematically reviewed animal experimental data for all reported inflammatory mediators. Meta-analyses of 352 studies revealed a strong increase in cytokines, chemokines, and growth factors, particularly 19 mediators in blood and 12 in burn tissue. Temporal kinetics showed long-lasting surges of proinflammatory cytokines in blood and burn tissue. Significant time-dependent effects were seen for IL-1β, IL-6, TGF-β1, and CCL2. The response of anti-inflammatory mediators was limited. Burn technique had a profound impact on systemic response levels. Large burn size and scalds further increased systemic, but not local inflammation. Animal characteristics greatly affected inflammation, for example, IL-1β, IL-6, and TNF-α levels were highest in young, male rats. Time-dependent effects and dissimilarities in response demonstrate the importance of appropriate study design. Collectively, this review presents a general overview of the burn-induced immune response exposing inflammatory pathways that could be targeted through immunotherapy for burn patients and provides guidance for experimental set-ups to advance burn research.
2018-05-23 | The Role of the Inflammatory Response in Burn Injury
Burns are characterised by significant local swelling and redness around the site of injury, indicative of acute inflammation. Whilst the inflammatory response is fundamental to the healing process, triggering a cascade of cytokines and growth factors to protect against the risk of infection, it is clear that prolonged inflammation can be detrimental and lead to scarring and fibrosis. Severe burns may display chronic, persistent inflammation long after the initial burn injury and may even result in multiple organ failure (MOF) due to systemic inflammatory response syndrome (SIRS). Excessive inflammation in the early stages of healing has been identified as a causative factor in the formation of scars which can be disfiguring, functionally restrictive and may require revisionary surgeries. Therefore, it is imperative that inflammation is effectively managed following burn injuries in order to optimise the benefits it provides whilst actively preventing the complications of inflammation including SIRS, multiple organ failure (MOF) and the development of scarring and fibrosis. Reviewing the current knowledge about the role of the inflammatory response in burns and the treatments available for the management of inflammation during wound healing, highlights the importance of continued research into understanding and developing new approaches to regulate inflammatory responses post-burn injuries.
2014-05-17 | Thrombospondin-1 and CD47 signaling regulate healing of thermal injury in mice
More than 2.5 million Americans suffer from burn injuries annually, and burn management is a major public health problem. Treatments have been developed to manage wound injuries employing skin grafts, various dressings and topical and systemic agents. However, these often achieve limited degrees of success. We previously reported that targeting the interaction of thrombospondin-1 with its signaling receptor CD47 or deletion of the genes encoding either of these proteins in mice improves recovery from soft tissue ischemic injuries as well as tissue injuries caused by ionizing radiation. We now demonstrate that the absence of CD47 improves the rate of wound closure for a focal dermal second-degree thermal injury, whereas lack of thrombospondin-1 initially delays wound closure compared to healing in wild type mice. Doppler analysis of the wounded area showed increased blood flow in both CD47 and thrombospondin-1 null mice. Accelerated wound closure in the CD47 null mice was associated with increased fibrosis as demonstrated by a 4-fold increase in collagen fraction. Wound tissue of CD47 null mice showed increased thrombospondin-1 mRNA and protein expression and TGF-β1 mRNA levels. Activation of latent TGF-β1 was increased in thermally injured CD47-null tissue as assessed by phosphorylation of the TGF-β1 receptor-regulated transcription factors SMAD-2 and -3. Overall these results indicate that targeting CD47 may improve the speed of healing thermal injuries, but some level of CD47 expression may be required to limit the long term TGF-β1-dependent fibrosis of these wounds.
2008-01-01 | Blockade of Thrombospondin-1-CD47 Interactions Prevents Necrosis of Full Thickness Skin Grafts
In Brief Background: Skin graft survival and healing requires rapid restoration of blood flow to the avascular graft. Failure or delay in the process of graft vascularization is a significant source of morbidity and mortality. One of the primary regulators of blood flow and vessel growth is nitric oxide (NO). The secreted protein thrombospondin-1 (TSP1) limits NO-stimulated blood flow and growth and composite tissue survival to ischemia. We herein demonstrate a role for TSP1 in regulating full thickness skin graft (FTSG) survival. Methods and Results: FTSG consistently fail in wild type C57BL/6 mice but survive in mice lacking TSP1 or its receptor CD47. Ablation of the TSP1 receptor CD36, however, did not improve FTSG survival. Remarkably, wild type FTSG survived on TSP1 null or CD47 null mice, indicating that TSP1 expression in the wound bed is the primary determinant of graft survival. FTSG survival in wild type mice could be moderately improved by increasing NO flux, but graft survival was increased significantly through antibody blocking of TSP1 binding to CD47 or antisense morpholino oligonucleotide suppression of CD47. Conclusions: TSP1 through CD47 limits skin graft survival. Blocking TSP1 binding or suppressing CD47 expression drastically increases graft survival. The therapeutic applications of this approach could include burn patients and the broader group of people requiring grafts or tissue flaps for closure and reconstruction of complex wounds of diverse etiologies. Thrombospondin-1 is a potent physiologic regulator of nitric oxide-driven blood flow and angiogenesis. This regulation requires the cell receptor CD47. In a murine model of skin graft survival we demonstrate that endogenous thrombospondin-1 limits graft survival via CD47 and targeting CD47 with antibodies or suppressing CD47 with a morpholino oligonucleotide enhances graft survival by blocking this pathway.
2006-05-01 | Interactions of Systemic Immune Response and Local Wound Healing in Different Burn Depths: An Experimental Study on Rats
This study aimed to clarify the local and systemic immune responses at different burn depths. Thirty female Sprague-Dawley rats were divided into three groups: full-thickness (F), partial-thickness (P), and Sham (S). Burns were induced on three separate areas on the dorsums of rats. Serum levels of interferon (IFN)-gamma; tumor necrosis factor-alpha; interleukin (IL)-1, IL-6, and IL-10 were measured once in controls and 1 hour after burn, 48 hours after burn, and 7 days after burn in F and P groups. Neutrophils, CD68-positive macrophages, HLA-DR-positive cells, and CD3-positive lymphocytes were graded semiquantitatively, and the wounds were examined once in shams and at 1 hour after burn, 48 hours after burn, and 7 days after burn in F and P groups. IL-6 levels were highest in F group, followed by P group 1 hour after burn. IFN-gamma levels were higher in the F group; IL-1 levels were higher in F and P groups at 1 hour after burn. Local accumulation of macrophages was similar in F and P groups. Lymphocytes were denser in P group at 1 hour after burn, and neutrophils were denser in F group at 7 days after burn. We suggest that early elevations of IL-6 and IFN-gamma prolong inflammation in full-thickness burns. Modulation of proinflammatory cytokines may improve burn wound treatment.
other
2023-06-09 | Investigating the relationship between transcriptomic markers, and burn wound healing and scarring outcomes
This study identified miRNAs, genes and biological pathways associated with wound healing and scarring in children with burn injuries. The miRNAs and genes which were associated with burn injury, burn severity, and burn scarring could be developed into future tools to predict wound healing and scarring outcomes, or new treatments to enhance burn wound healing.
2022-01-01 | The role of b1 methylation, physiologic replication independent endogenous dna double strand breaks (phy-rind-edsb) and laminin 511 e8 proteins in rat second degree burn wound healing
Background: DNA methylation via short interspersed nuclear element (SINE) small interfering (si)RNA prevents DNA damage and promotes cell proliferation. Furthermore, laminin ?5 ?1 ?1(LM511) is an extracellular structural protein that can support epithelial cell adhesion and migration. Box A of high-mobility group box 1 protein (Box A of HMGB1) is a common nuclear protein in eukaryotic cells that can reduce DNA damage response toward burn injury.
Objective: To investigate whether treatment of burn wounds using B1 siRNA, Box A of HMGB1 and LM511-E8 fragment improved wound closure in a rat second-degree burn wound model.
Methods: �I performed a cross-sectional analytical study using tissue and blood samples from post-burn and healthy patients (n = 23 each) to measure Alu methylation levels and patterns. In in vivo experiments, second-degree burn wounds were introduced on the backs of rats. The rats were then divided into control and experiment groups: a B1 siRNA-treated, Box A of HMGB1 protein and LM511-E8, saline-treated control, and calcium phosphate-nanoparticle-treated control group (n = 1520/group). The wounds were imaged on days 0, 7, 14, 21, and 28 post-injuries. The tissue sections were processed for methylation and histological and immunohistochemical examination and scored based on the overall expression of histone H2AX phosphorylated on serine 139 (?H2AX), 8-hydroxy-2?-deoxyguanosine (8-OHdG), and presence of cytokeratin 10 and 14.
Results: Alu methylation levels were lower in hypertrophic scar tissues than in normal skin (29.4 ? 2.5% vs. 35.6? 3.2%, P = 0.0002). Burn wound closure improved in the B1 siRNA-treated group compared to that in the control group, especially from days 14 to 28 post-injury (P < 0.001). The overall pathological score and degree of B1 methylation in the B1 siRNA-treated group improved at days 1428 days post-injury. The Box A of HMGB1 protein group demonstrated improvement in burn wound closure, starting from day 7th until day 28th after injury (P < 0.001). Furthermore, ?H2AX and 8-OHdG expression in the HMGB1 plasmid-treated group was lower than that in the control group (P < 0.05). The re-epithelialisation in the LM511-E8-treated group was quicker than that of the control group at 728 days post-injury, with the largest improvement observed on days 7 and 14 (P < 0.001). The pathological score of the LM511-E8-treated group was higher than that of the control group at 1428 days post-injury.
Conclusion: These results imply that LM511-E8 fragment, B1 siRNA, and Box A of High-mobility group box 1 protein (Box A of HMGB1) are promising therapeutic options for managing second-degree burns.
2014-02-28 | Response of human skin to esthetic scarification
This study was undertaken to investigate changes in RNA expression in previously healthy adult human skin following thermal injury induced by contact with hot metal that was undertaken as part of esthetic scarification, a body modification practice. Subjects were recruited to have pre-injury skin and serial wound biopsies performed. 4 mm punch biopsies were taken prior to branding and 1 h, 1 week, and 1, 2 and 3 months after injury. RNA was extracted and quality assured prior to the use of a whole-genome based bead array platform to describe expression changes in the samples using the pre-injury skin as a comparator. Analysis of the array data was performed using k-means clustering and a hypergeometric probability distribution without replacement and corrections for multiple comparisons were done. Confirmatory q-PCR was performed. Using a k of 10, several clusters of genes were shown to co-cluster together based on Gene Ontology classification with probabilities unlikely to occur by chance alone. OF particular interest were clusters relating to cell cycle, proteinaceous extracellular matrix and keratinization. Given the consistent expression changes at 1 week following injury in the cell cycle cluster, there is an opportunity to intervene early following burn injury to influence scar development.
2006-06-08 | A Role for the Mitogen-activated Protein Kinase Kinase Kinase 1 in Epithelial Wound Healing
The mitogen-activated protein kinase kinase (MEK) kinase 1 (MEKK1) mediates activin B signals required for eyelid epithelium morphogenesis during mouse fetal development. The present study investigates the role of MEKK1 in epithelial wound healing, another activin-regulated biological process. In a skin wound model, injury markedly stimulates MEKK1 expression and activity, which are in turn required for the expression of genes involved in extracellular matrix (ECM) homeostasis. MEKK1 ablation or down-regulation by interfering RNA significantly delays skin wound closure and impairs activation of Jun NH 2 -terminal kinases, induction of plasminogen activator inhibitor (PAI)-1, and restoration of cell–cell junctions of the wounded epidermis. Conversely, expression of wild-type MEKK1 accelerates reepithelialization of full-thickness skin and corneal debridement wounds by mechanisms involving epithelial cell migration, a cell function that is partially abolished by neutralizing antibodies for PAI-1 and metalloproteinase III. Our data suggest that MEKK1 transmits wound signals, leading to the transcriptional activation of genes involved in ECM homeostasis, epithelial cell migration, and wound reepithelialization.
proteins
2026-07-29 | Bromelain-based enzymatic debridement versus standard of care in deep partial- and full-thickness burns: A systematic review and meta-analysis of randomized controlled trials.
Management of debridement-eligible thermal burns requires accurate removal of devitalized tissue. Tangential excision remains limited by imprecise depth assessment beneath opaque eschar, risking unintended dermal sacrifice. Bromelain-based enzymatic debridement (BBD) has emerged as an alternative; however, its impact on patient-level surgical outcomes has not been rigorously quantified in randomized trials. A systematic review and meta-analysis of randomized trials compared BBD with standard of care (SOC) in acute deep thermal burns. The primary outcome was the proportion requiring surgical excision. Random-effects models pooled effects. A prespecified sensitivity analysis evaluated a wound-level trial. Risk of bias was assessed using the Cochrane RoB 2 tool. Five randomized trials met criteria. Four reporting per-patient outcomes contributed to the primary meta-analysis (n = 336). BBD reduced surgical excision versus SOC (RR, 0.11; 95% CI, 0.06-0.23; I² = 0%), corresponding to an absolute risk reduction of 65% and a number needed to treat of 1.5. BBD was also associated with reduced autograft use, shorter time to debridement, and comparable or improved blinded scar assessments at 12 months. Open-label design was the principal source of potential bias. Sensitivity analysis including the wound-level trial preserved effect direction with increased heterogeneity. Randomized evidence demonstrates that, in early-treated debridement-eligible burns with limited total body surface area burned (TBSA), BBD reduces operative and graft burden without compromising wound closure or long-term remodeling. Future trials incorporating blinded operative endpoint adjudication, objective assessment of dermal preservation and broader clinical outcomes will further clarify treatment effect and optimize patient selection.
2026-03-27 | Histopathological Changes Following Bromelain-Based Enzymatic Debridement (NexoBrid®): A Comprehensive Systematic Review of Preclinical and Clinical Evidence.
Background: NexoBrid® (NXB; MediWound Ltd., Yavne, Israel) (anacaulase-bcdb) is a bromelain-based enzymatic debriding agent approved for eschar removal in burn care. Despite widespread clinical use, histological evidence of tissue-level changes after enzymatic debridement remains limited. This systematic review aimed to evaluate preclinical and clinical studies describing histological findings following bromelain-based enzymatic debridement of thermal burns. Methods: Following PRISMA 2020 guidelines, we performed parallel systematic searches of preclinical (animal) and clinical (human) studies across PubMed, Embase, CENTRAL, Web of Science, and Scopus. Included studies reported thermal burns treated with bromelain-based enzymatic debridement and tissue biopsies with histological analysis. Quality was assessed using the SYRCLE Risk of Bias Tool (preclinical) and JBI Critical Appraisal Checklists (clinical). Results: Six preclinical studies (five porcine, one rat) met inclusion criteria. Findings included: selective eschar removal with dermal preservation; protection of the zone of stasis (67% partial- vs. 100% full-thickness necrosis; p = 0.05); viable dermal thickness of 1.1 ± 0.7 mm; and accelerated re-epithelialization (7.4 ± 0.8 vs. 9.1 ± 2.1 days; p < 0.05). Only two clinical studies (n = 9 patients) met the inclusion criteria: one case series (n = 8) and one case report. Clinical findings showed upper dermal homogenisation with preserved deep dermis, vascular congestion correlating with pinpoint bleeding, and pseudoeschar formation via transepidermal elimination. Conclusions: Preclinical evidence supports selective enzymatic debridement with dermal preservation. However, clinical histological data are limited to nine patients after over 13 years of use. This highlights a critical translational gap and underscores the need for prospective clinical histological studies.
2026-03-01 | 1011. Case Study. Bovine Collagen Dermal Matrix Facilitates Re-epithelialization in Mixed Partial-thickness Burn Wounds: A Case Series
Abstract Patient Presentation (age range, injury details, relevant history) This case series describes two male patients aged 61 and 75 years, with multiple comorbidities and mixed partial-thickness thermal burns measuring approximately 100 cm2 and 300 cm2 on the left forearm and right lower extremity, respectively. Clinical Challenges In burn and wound management, cutting-edge interventional studies and emerging technologies are most often applied to full-thickness and deep partial thickness injuries requiring surgical closure. In contrast, superficial and mixed partial-thickness wounds are typically managed more conservatively and receive less attention in interventional literature. This relative gap in evidence-based innovation may affect therapeutic options and delay healing for patients who fall into such category. By exploring new technologies such as bovine collagen based dermal matrix (BCDM), there is an opportunity to expand treatment paradigms for these patients. To illustrate the potential role of this approach, we present these two patients with mixed partial-thickness burns successfully treated with a novel BCDM. Management Approach After initial wound care and debridement using a combination of sharp excision and hydrotherapy, a bovine collagen–based dermal matrix (BCDM) was applied at bedside directly to the wounds. Post-application wound management consisted of a primary non-adherent dressing layer, followed by compressive layers (Patient 1) or negative pressure wound therapy (NPWT) (Patient 2). Dressings for both were removed at 7 days post-application and were subsequently switched to antimicrobial ointment, non-adherent contact layer and compressive outer dressings. Both patients were monitored weekly for re-epithelialization, complications, and overall wound healing. Outcomes Patient 1 achieved complete re-epithelialization within 4 weeks without complications or the need for autografting. Patient 2 was ready for autograft at first dressing change, however he was lost to follow up until he returned at 4 weeks with a fully healed wound. Post-application wound care was straightforward, and both patients reported satisfaction with cosmetic and functional outcomes, particularly with the avoidance of operative intervention. Lessons Learned This case series demonstrates that BCDM can be an effective treatment option for mixed partial thickness burns, promoting timely healing while minimizing patient morbidity and possibly eliminating the need for grafting. These early findings suggest that collagen-based dermal matrices may expand the role of advanced biologics beyond full-thickness injuries, offering a valuable alternative in the management of selected partial-thickness burns. Applicability to Practice The use of BCDM in outpatient or bedside settings may reduce the need for operative procedure and improve patient-centered outcomes in partial thickness burn management.
2026-03-01 | 830. A Bovine Dermal Collagen Matrix for Deep Partial-thickness Burns: A Case Series
Abstract Introduction Dermal matrices have become an integral part of modern burn care due to their ability to reduce pain, enhance cosmesis, and restore function in full-thickness wounds. In the context of deep partial-thickness wounds, dermal matrices can serve as an advanced dressing option to support re-epithelialization, potentially eliminating the need for traditional autografting. A bovine dermal collagen matrix (BDCM) comprised of crosslinked, type I and type III collagen has demonstrated effectiveness in supporting rapid cellular infiltration and vascular tissue formation in porcine full-thickness wounds preclinically as well as facilitating early autograft readiness in two recent clinical cases. Building on its utility in full-thickness wounds, our institution was the first to evaluate the clinical efficacy of BDCM as an advanced dressing in deep partial-thickness burns. Methods A retrospective chart review was conducted from March to May 2025 to evaluate the safety and effectiveness of BDCM in 3 patients with deep partial-thickness burns. Outcomes assessed included matrix integration, time to re-epithelialization, extent of repigmentation in treated areas, and pain assessment. Results In case 1, an 18-year-old male with a 3% total body surface area (TBSA) deep partial-thickness grease burn to the right lower leg, ankle, and foot was treated with BDCM in combination with a skin cell suspension autograft (SCSA). He was discharged on post-operative day (POD) 1 with full ambulation and a night splint. On POD 6, the BDCM had fully integrated, with epidermal budding and minimal open areas; the patient reported no pain. On POD 13, 100% re-epithelialization was noted, and melanin pigment had begun to return. In case 2, a 51-year-old male had a 0.5% TBSA deep partial-thickness chemical burn to bilateral hands and wrists. On POD 7, the BDCM had fully integrated with one small open area on the fifth digit. Complete (100%) re-epithelialization was achieved by POD 20. In case 3, a 33-year-old male with an 8% TBSA deep partial-thickness scald burn to bilateral lower extremities was treated with BDCM and SCSA. On POD 8, the BDCM had mostly incorporated with 95% re-epithelialization. By POD 15, early repigmentation was noted. Conclusions These cases demonstrate the safety and efficacy of the BDCM in supporting healing of deep partial-thickness burns. Importantly, the BDCM supported re-epithelialization and repigmentation, thus offering a more diverse treatment option within burn care for deep partial-thickness injuries. Additionally, patients experienced reduced pain post-application and simplified aftercare, further highlighting the clinical utility of the BDCM. Applicability of Research to Practice BDCM is a safe and viable advanced dressing option for healing deep partial-thickness burns. Funding for the study N/A.
2025-12-23 | Burn Classification, Total Body Surface Area Assessment, And Epidemiology: Foundations For Modern Burn Care
characterized by tissue destruction, systemic inflammatory response, metabolic derangements, and potential multiorgan dysfunction. Despite advances in prevention and treatment, burns continue to pose a significant global health burden. Early and accurate assessment of burn depth and extent remains the cornerstone of effective management, directly influencing triage decisions, fluid resuscitation strategies, need for surgical intervention, and referral to specialized burn centers. This article reviews burn classification by depth, methodologies for estimating total body surface area (TBSA), global epidemiological patterns, and the clinical relevance of accurate initial burn evaluation in contemporary practice. Classification of Burns by Depth Burn depth reflects the degree of tissue destruction and the regenerative capacity of the skin, making it one of the strongest predictors of healing time, infection risk, scarring, and functional outcome. Superficial (First-Degree) Burns are limited to the epidermis. Clinically, they present with erythema, tenderness, and dry skin without blistering. Capillary refill is preserved, and pain is prominent due to intact nerve endings. These burns heal within days through epidermal regeneration and do not result in scarring. Superficial Partial-Thickness (Second-Degree) Burns involve the epidermis and superficial dermis. They are characterized by blister formation, moist appearance, severe pain, and brisk capillary refill. Because epithelial appendages such as hair follicles and sweat glands remain intact, spontaneous re-epithelialization occurs rapidly, usually within two to three weeks, with minimal scarring. Deep Partial-Thickness (Second-Degree) Burns extend deeper into the dermis, damaging a greater proportion of dermal structures. These burns often appear mottled, pale, or erythematous, with diminished sensation and sluggish capillary refill. Healing is prolonged and unpredictable, frequently exceeding three weeks, which increases the risk of hypertrophic scarring and contractures. Surgical excision and grafting are commonly required. Full-Thickness (Third-Degree) Burns involve complete destruction of the epidermis and dermis. The affected tissue appears dry, leathery, and insensate due to nerve destruction. Because no epithelial elements remain, spontaneous healing is not possible, and definitive management requires early excision and skin grafting to reduce infection risk and improve outcomes. Fourth-Degree Burns extend beyond the skin into underlying fascia, muscle, tendon, or bone. These devastating injuries are often associated with high-energy mechanisms and severe systemic insult. Management is complex and may necessitate limb amputation, staged reconstruction, or palliative approaches depending on patient condition and associated injuries.1
small molecules
2026-03-10 | Evaluation of Burn Depth using Indocyanine Green: Discrepancies Between Macroscopic Visualization and the Microenvironment.
Burn wound management is guided by the depth of dermal tissue damage. Standard practice for this depth assessment is daily visual evaluation of the wound by an experienced burn surgeon, which is inherently subjective and at times inaccurate. Perioperative fluorescence imaging with indocyanine green (ICG) has emerged as a potential tool to objectively evaluate burn depth. The current study aims to explore the relationship between ICG angiography (ICGA), Second-window ICG (SWIG), and burn depth, with the goal of understanding how this technology could guide the prognosis and treatment of human burn wounds. Patients (n = 14) with indeterminate depth or deep partial thickness burns received an infusion of ICG on post-burn day 2-3 or the day before surgery. Imaging was performed immediately after injection for angiography as well as the following day for SWIG. A full-thickness tissue biopsy was obtained for histologic evaluation. In vitro primary human fibroblasts and keratinocytes were cultured, subjected to heat injury (65 deg C for 2.5 or 5 minutes), and incubated with ICG. Flow cytometry was used to classify the cells as live, apoptotic, or necrotic based and to quantify ICG uptake. ICGA perfusion parameters are increased in burn wounds that did not require grafting and ICGA egress slope correlates to SWIG fluorescence intensity. Furthermore, SWIG microscopic fluorescence intensity correlates to histologic burn depth and colocalizes in necrotic region of burn injury, however there is high interpatient variability between SWIG fluorescence intensity and histologic burn depth, predicted healing potential, and graft status. Flow cytometric analysis of in vitro skin cells shows that preferential ICG binding to necrotic cells contributes to SWIG signal in a burn, with binding influenced by cell type and injury severity. Overall, this study suggests that fluorescence imaging has the potential to aid in the assessment of healing potential, although current challenges related to imaging variability, interpretation, and clinical integration must be addressed to optimize its utility in burn management.Clinical trials number: NCT05593523.
2024-03-14 | Natural Compounds and Biomimetic Engineering to Influence Fibroblast Behavior in Wound Healing
Throughout history, natural products have played a significant role in wound healing. Fibroblasts, acting as primary cellular mediators in skin wound healing, exhibit behavioral responses to natural compounds that can enhance the wound healing process. Identifying bioactive natural compounds and understanding their impact on fibroblast behavior offers crucial translational opportunities in the realm of wound healing. Modern scientific techniques have enabled a detailed understanding of how naturally derived compounds modulate wound healing by influencing fibroblast behavior. Specific compounds known for their wound healing properties have been identified. Engineered biomimetic compounds replicating the natural wound microenvironment are designed to facilitate normal healing. Advanced delivery methods operating at micro- and nano-scales have been developed to effectively deliver these novel compounds through the stratum corneum. This review provides a comprehensive summary of the efficacy of natural compounds in influencing fibroblast behavior for promoting wound regeneration and repair. Additionally, it explores biomimetic engineering, where researchers draw inspiration from nature to create materials and devices mimicking physiological cues crucial for effective wound healing. The review concludes by describing novel delivery mechanisms aimed at enhancing the bioavailability of natural compounds. Innovative future strategies involve exploring fibroblast-influencing pathways, responsive biomaterials, smart dressings with real-time monitoring, and applications of stem cells. However, translating these findings to clinical settings faces challenges such as the limited validation of biomaterials in large animal models and logistical obstacles in industrial production. The integration of ancient remedies with modern approaches holds promise for achieving effective and scar-free wound healing.
2023-12-29 | ANTIOXIDANTS SUPPLEMENTATION BASED ON NATURAL PRODUCTS IN THE TREATMENT OF THE THERMAL SKIN INJURY
Thermal injuries are a major medical, economic and social problem, whose severity, morbidity, mortality, prognosis and treatment outcome directly depend on the surface and depth of the burn, but also on the patient's age, health status and accompanying complications. The treatment of thermal injury is long and complex, and the outcome is often uncertain with a very complex rehabilitation process, because the injury damages both physical and psychological health. Constant innovations in the protocol of medical treatment and the search for new mechanisms involved in the pathogenesis of burns can be helpful in successful treatment. Therefore, there is a constant search for adjuvant therapies that will improve results like HBO, AO, platelet- rich plasma, negative pressure wound therapy and others. In recent years, the application of antioxidants as adjuvant therapy for the care and treatment of wounds has been the subject of various researche. Antioxidants are biologically active molecules that prevent the creation of free radicals in the body and at the same time neutralize the existing ones, this way participating in maintaining the oxidative status at the desired level. Antioxidant -rich natural products may provide a solution to improve wound healing. The application of antioxidant therapy has shown numerous benefits in improving the outcome of burns. However, more information is needed from the clinical trials on the use of natural products, especially in combination with other therapies. Keywords: thermal skin injury, hyperbaric oxygen therapy, antioxidant rich natural products
2023-12-27 | Temperature and pH-sensitive chitosan-collagen hydrogels for antimicrobial and wound healing applications
Hydrogels have proven to be of great value because of their useful properties and functions. Temperature and pH-sensitive chitosan-collagen-based hydrogels have drawn research interest in the area of wound care. Their unique mechanism allows them to release antimicrobial agents in response to changes in the environment and aids in efficient healing of wounds. The current review aims to describe various composite hydrogels of chitosan and collagen, their temperature and pH sensitivity, the antimicrobial effect of chitosan-collagen hydrogels and their applications in wound healing. Sources and properties of chitosan and collagen have also been stated in order to highlight their importance in these hydrogels. The main focus revolves around the potential of chitosan-collagen hydrogels as antimicrobial biomaterials for healing wounds in an efficient manner.
2023-11-07 | The Use of Carboxytherapy for the Treatment of Deep Partial-Thickness Skin Burns After Circumferential and High-Definition Liposuction: Promising Clinical Results in 5 Consecutive Cases
Abstract Background Literature on skin burn treatment after liposuction is limited. To date, no publication has discussed possible treatments for this complication despite its relatively frequent incidence. Objectives The objective of this study is to report the early experiences of the use of carboxytherapy for the treatment of Grade IIB partial-thickness skin burns after liposuction. We aim to analyze its potential beneficial effects on wound healing and skin pigmentation, without the need for additional corrective surgery or permanent scarring. Methods Five patients who showed Grade IIB skin burns within 24 h after circumferential and high-definition liposuction were treated with carboxytherapy. Wound healing was evaluated after 1 and 2 weeks. Scar formation and skin pigmentation were evaluated after 3 months. Results Carboxytherapy treatments were either performed every day or every other day for 1 or 2 weeks, depending on the wound healing. At 2 weeks postoperatively, all skin burns showed complete or near-complete healing. At 3 months, there were no zones of hypertrophic scarring or skin contracture. No complications with regard to the carboxytherapy treatment were observed. Conclusions Carboxytherapy is an easy-to-use, affordable, and safe treatment for Grade IIB skin burns postliposuction. Its known influence on neo-angiogenesis and oxygen release in a hypoxic environment has beneficial effects on wound healing and avoidance of hypertrophic scarring and skin hyperpigmentation after skin burns. It can potentially become a useful addition for surgeons who perform liposuction and body contouring. Further studies with larger numbers of patients are necessary to determine its full potential. Level of Evidence: 4
cell therapies
2026-06-22 | The Use of Kerecis Omega3 Wound Fish Skin Graft for the Treatment of Deep Burn Wounds.
Addressing deep partial-thickness burns (DPTBs) and full-thickness burns (FTBs) remains a significantly challenging task in modern burn surgery. Among a broad lineup of wound products, biological adjuncts like fish skin-derived scaffolds offer unique regenerative properties, presenting new possibilities in complex wound management. We herein report our institutional clinical experience with the fish skin-based scaffold Kerecis Omega3 Wound. This retrospective, single-center case series evaluated all patients with DPTBs and FTBs treated with Kerecis Omega3 Wound between 2020 and 2024 at the burn center of the University Hospital Zurich. The specific indications for intervention, depth of burn injury, anatomical regions of application, subsequent need for further surgery, and short- and long-term complications were systematically assessed. Twenty-seven patients were reviewed, exhibiting a mean affected total body surface area of 35.73% and an average abbreviated burn severity index score of 7.74. Fish skin was used in an acute setting in 21 cases; for the remaining cases, it was used for chronic wound-healing disturbances following burn injury. The most frequently treated anatomical region was the upper extremity. Almost 50% of the DPTB wounds healed spontaneously following treatment with Kerecis Omega3 Wound. Conversely, all FTBs required further skin grafting or other reconstructive measures. Postsurgical infections occurred in 4 patients, necessitating the removal of the product. Contractures were observed in 3 patients with FTBs during clinical follow-up. Kerecis Omega3 Wound represents a valuable adjunct for wound conditioning in patients with DPTBs, either as a preparation before skin grafting or to stimulate spontaneous wound regeneration. Regarding FTBs, its efficacy in restoring the dermal layer requires further research and clinical validation.
2026-03-01 | 1013. Case Study. Fish Skin Grafts for Partial-thickness Electrical Burns: A Mini Case Series of Successful Outcomes
Abstract Patient Presentation (age range, injury details, relevant history) A 27-year-old and 36-year-old healthy Hispanic male with Fitzpatrick type IV skin sustained 1% electrical burns to their left (non-dominant) hands during a construction accident. The 27-year-old had superficial and deep second-degree burns to dorsal digits 3-5 (including PIP and DIP joints), with near circumferential wrist involvement. The 36-year-old had superficial second-degree burns to all dorsal digits (including MCP, PIP, and DIP joints) and volar wrist involvement. Clinical Challenges Deep partial thickness burns spanning multiple joints. The goal was to reduce scarring and optimize hand function, focusing on a quick return to work, effective pain management, and brief hospitalization. Management Approach Both patients underwent 5 days of local wound care followed by tangential excision and piscine xenograft coverage. Wound care included twice daily cleansing, Silvadene application, gauze wrap, elastic compression and elevation. Occupational therapy was consulted. Tangential excision was performed with a Goulian blade, followed by the application of piscine xenografts fixed with staples. Sterile dressings included antibiotic ointment, gauze wrap, and an elastic compression bandage. Both patients were discharged with one-week follow-up for dressing changes. Outcomes A mini case series with terrific cosmetic and functional outcomes while providing prompt coverage of a raw wound, thus minimizing pain. Piscine xenograft was pursued in lieu of autograft due to the superficial partial thickness depth. The piscine dermal matrix offered the additional benefits of modulating inflammation, promoting neovascularization and reinforcing the dermal construct with natural collagen, elastin, glycosaminoglycans and extracellular membrane components resulting in a more pliable neodermis. At 1 week post-op, full graft incorporation was noted in deeper areas, while more superficial injuries exhibited partial graft loss as dry, scaly tissue. Neither patient required narcotics postoperatively. Both had some restricted grip formation, more pronounced in the younger male. They were provided wound care, hand exercises, and outpatient occupational therapy prescriptions. At 2 weeks post-op, both patients had full epithelialization, no hypertrophy, and improved range of motion. Wound care transitioned to moisturizing, and they were provided compression gloves and sun exposure precautions. They returned to work at this time without functional deficits. At 7 months post-op, both patients had excellent cosmetic outcomes and regained native functionality, with no hypertrophy or contracture. The patients' lack of co-morbidities and good nutritional status likely aided healing. Lessons Learned In appropriate cases, piscine xenografts can achieve timely wound healing with optimal tissue pliability and cosmesis without the need for autograft, thus reducing procedural time, minimizing pain, and avoiding donor site morbidity. Applicability to Practice:
2025-10-15 | Consensus Recommendations for Intact Fish Skin Graft in the Management of Burn Injury
Background: Intact fish skin graft (IFSG) derived from North Atlantic cod emerged as a treatment for burns in 2019. This consensus paper presents the best to date evidence and experience-based recommendations from eight U.S. burn care experts regarding optimal use of IFSG across different burn depths and wound types. Methods: Eight U.S. burn specialists with routine IFSG experience conducted a two cycle modified Nominal Focus Group. A systematic literature search (through April 2024) was conducted, followed by informed discussion, and the generation of consensus statements. Consensus was defined as ≥80 % agreement on a 5 point Likert scale. Results: Full or strong consensus (≥80 %) was reached on 12/15 statements. IFSG is recommended for: mid-dermal & deep-dermal partial-thickness burns (as definitive treatment), full thickness traumatic & burn wounds (in a 2-stage procedure before split-thickness skin graft). IFSG is not routinely recommended for purely epidermal burns. Based on recommendations from panelists, IFSG should be applied immediately after thorough debridement except in traumatic wounds when IFSG application should be delayed until clear demarcation and resolution of any infection. Reapplication is rarely required and, if needed, should occur 6–10 days after the initial graft. For wounds >100 cm², negative pressure wound therapy (NPWT) is the preferred bolster. The panel agreed IFSG accelerates readiness for STSG, decreases procedural pain, and can reduce nursing burden and overall cost of care. Recommendations: Clinicians should reserve IFSG for deep-dermal or full thickness burns and traumatic wounds and should pair IFSG with NPWT for large areas. IFSG is not needed in superficial burns that heal adequately with standard care. Prospective trials in deep-dermal partial thickness and full thickness burns remain a priority.
2024-11-13 | Management of Large Full-Thickness Burns Using Kerecis™ Acellular Fish Skin Graft and ReCell™ Autologous Skin Cell Suspension: A Case Report of Two Patients with Large Surface Area Burns.
Novel treatments for extensive full-thickness burns revolve around fluid control, addressing systemic inflammatory derangements, and achieving early skin coverage with acceptable cosmetic and functional results. Recent advances in the management of extensive burns include fish skin xenografts, such as Kerecis Omega-3 acellular dermal substitute. Reported to be non-allergenic and antimicrobial, this Atlantic Cod skin derivative has the potential to supplement the management of patients with large surface area burns. A chart review was performed on two complex patients. Patient 1 suffered 65% partial and full-thickness burns after lighting herself on fire with gasoline, and patient 2 suffered 86% partial and full-thickness burns following a methamphetamine explosion. The patients were both treated with a multi-step process using cadaveric allografts, Kerecis acellular fish skin placement, and autologous split-thickness skin grafts (STSG). Case 2 utilized ReCell autologous skin cell suspension and Novosorb bilaminate dermal substitute (BTMTM) due to limited donor sites. Complete coverage and epithelization were achieved on both patients but required multiple reapplications of autograft and Kerecis. Contractures of the neck, elbows, and hand were present in Case 1. Kerecis xenografting may have an expanding role in burn management due to standalone capabilities for deep partial-thickness burns and ease of use. Further evaluation is needed to establish the most optimal timing of use and best zones of application to improve take and reduce contractures.
2024-04-17 | 810 Development of a Porcine Burn Wound Model
Abstract Introduction Deep partial thickness burns generally require more than 2-3 weeks to heal often resulting in hypertrophic scarring and patient morbidity. Because the skin of pigs most closely resembles that of humans, the pig is often used as an experimental burn wound model. We describe the development of a reproducible burn wound model in Yorkshire pigs. Methods We created standardized 5 x 5 cm burns on the backs and flanks of anesthetized domestic pigs (30 kg) using a radiant heating device set at 600 degrees C and applied to the animal’s skin for 5, 10, or 15 seconds. Full thickness 4 mm punch biopsies were obtained from the burns at 4 and 24 hours for burn depth evaluation. The tissue sections were stained with Hematoxylin and Eosin, HMGB-1 (a marker of necrosis) and activated cleaved caspase 3 (a marker of apoptosis). The tissue sections were viewed by a board-certified dermatopathologist blinded to duration of exposure. The primary outcome was the deepest level of injury to the blood vessels or epithelial appendices (hair follicles or apocrine glands). Results Exposure of the pigs’ skin to the heating device for periods of 5, 10, and 15 seconds resulted in superficial partial, deep partial and full thickness burns respectively. Average depth of dermal injury 24 hours after exposure was 0.4 mm, 1.3 mm, and 2.4 mm for exposure times of 5, 10 and 15 seconds respectively. Conclusions We describe a standardized porcine model for creating reproducible superficial partial, deep partial and full thickness burns. Applicability of Research to Practice This model is now being used to investigate novel therapies for deep burns.
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2023-10-07 | Kinetics of Inflammatory Mediators in the Immune Response to Burn Injury: Systematic Review and Meta-Analysis of Animal Studies
Burns are often accompanied by a dysfunctional immune response, which can lead to systemic inflammation, shock, and excessive scarring. The objective of this study was to provide insight into inflammatory pathways associated with burn-related complications. Because detailed information on the various inflammatory mediators is scattered over individual studies, we systematically reviewed animal experimental data for all reported inflammatory mediators. Meta-analyses of 352 studies revealed a strong increase in cytokines, chemokines, and growth factors, particularly 19 mediators in blood and 12 in burn tissue. Temporal kinetics showed long-lasting surges of proinflammatory cytokines in blood and burn tissue. Significant time-dependent effects were seen for IL-1β, IL-6, TGF-β1, and CCL2. The response of anti-inflammatory mediators was limited. Burn technique had a profound impact on systemic response levels. Large burn size and scalds further increased systemic, but not local inflammation. Animal characteristics greatly affected inflammation, for example, IL-1β, IL-6, and TNF-α levels were highest in young, male rats. Time-dependent effects and dissimilarities in response demonstrate the importance of appropriate study design. Collectively, this review presents a general overview of the burn-induced immune response exposing inflammatory pathways that could be targeted through immunotherapy for burn patients and provides guidance for experimental set-ups to advance burn research. Burns are often accompanied by a dysfunctional immune response, which can lead to systemic inflammation, shock, and excessive scarring. The objective of this study was to provide insight into inflammatory pathways associated with burn-related complications. Because detailed information on the various inflammatory mediators is scattered over individual studies, we systematically reviewed animal experimental data for all reported inflammatory mediators. Meta-analyses of 352 studies revealed a strong increase in cytokines, chemokines, and growth factors, particularly 19 mediators in blood and 12 in burn tissue. Temporal kinetics showed long-lasting surges of proinflammatory cytokines in blood and burn tissue. Significant time-dependent effects were seen for IL-1β, IL-6, TGF-β1, and CCL2. The response of anti-inflammatory mediators was limited. Burn technique had a profound impact on systemic response levels. Large burn size and scalds further increased systemic, but not local inflammation. Animal characteristics greatly affected inflammation, for example, IL-1β, IL-6, and TNF-α levels were highest in young, male rats. Time-dependent effects and dissimilarities in response demonstrate the importance of appropriate study design. Collectively, this review presents a general overview of the burn-induced immune response exposing inflammatory pathways that could be targeted through immunotherapy for burn patients and provides guidance for experimental set-ups to advance burn research.
2018-05-23 | The Role of the Inflammatory Response in Burn Injury
Burns are characterised by significant local swelling and redness around the site of injury, indicative of acute inflammation. Whilst the inflammatory response is fundamental to the healing process, triggering a cascade of cytokines and growth factors to protect against the risk of infection, it is clear that prolonged inflammation can be detrimental and lead to scarring and fibrosis. Severe burns may display chronic, persistent inflammation long after the initial burn injury and may even result in multiple organ failure (MOF) due to systemic inflammatory response syndrome (SIRS). Excessive inflammation in the early stages of healing has been identified as a causative factor in the formation of scars which can be disfiguring, functionally restrictive and may require revisionary surgeries. Therefore, it is imperative that inflammation is effectively managed following burn injuries in order to optimise the benefits it provides whilst actively preventing the complications of inflammation including SIRS, multiple organ failure (MOF) and the development of scarring and fibrosis. Reviewing the current knowledge about the role of the inflammatory response in burns and the treatments available for the management of inflammation during wound healing, highlights the importance of continued research into understanding and developing new approaches to regulate inflammatory responses post-burn injuries.
2014-05-17 | Thrombospondin-1 and CD47 signaling regulate healing of thermal injury in mice
More than 2.5 million Americans suffer from burn injuries annually, and burn management is a major public health problem. Treatments have been developed to manage wound injuries employing skin grafts, various dressings and topical and systemic agents. However, these often achieve limited degrees of success. We previously reported that targeting the interaction of thrombospondin-1 with its signaling receptor CD47 or deletion of the genes encoding either of these proteins in mice improves recovery from soft tissue ischemic injuries as well as tissue injuries caused by ionizing radiation. We now demonstrate that the absence of CD47 improves the rate of wound closure for a focal dermal second-degree thermal injury, whereas lack of thrombospondin-1 initially delays wound closure compared to healing in wild type mice. Doppler analysis of the wounded area showed increased blood flow in both CD47 and thrombospondin-1 null mice. Accelerated wound closure in the CD47 null mice was associated with increased fibrosis as demonstrated by a 4-fold increase in collagen fraction. Wound tissue of CD47 null mice showed increased thrombospondin-1 mRNA and protein expression and TGF-β1 mRNA levels. Activation of latent TGF-β1 was increased in thermally injured CD47-null tissue as assessed by phosphorylation of the TGF-β1 receptor-regulated transcription factors SMAD-2 and -3. Overall these results indicate that targeting CD47 may improve the speed of healing thermal injuries, but some level of CD47 expression may be required to limit the long term TGF-β1-dependent fibrosis of these wounds.
2008-01-01 | Blockade of Thrombospondin-1-CD47 Interactions Prevents Necrosis of Full Thickness Skin Grafts
In Brief Background: Skin graft survival and healing requires rapid restoration of blood flow to the avascular graft. Failure or delay in the process of graft vascularization is a significant source of morbidity and mortality. One of the primary regulators of blood flow and vessel growth is nitric oxide (NO). The secreted protein thrombospondin-1 (TSP1) limits NO-stimulated blood flow and growth and composite tissue survival to ischemia. We herein demonstrate a role for TSP1 in regulating full thickness skin graft (FTSG) survival. Methods and Results: FTSG consistently fail in wild type C57BL/6 mice but survive in mice lacking TSP1 or its receptor CD47. Ablation of the TSP1 receptor CD36, however, did not improve FTSG survival. Remarkably, wild type FTSG survived on TSP1 null or CD47 null mice, indicating that TSP1 expression in the wound bed is the primary determinant of graft survival. FTSG survival in wild type mice could be moderately improved by increasing NO flux, but graft survival was increased significantly through antibody blocking of TSP1 binding to CD47 or antisense morpholino oligonucleotide suppression of CD47. Conclusions: TSP1 through CD47 limits skin graft survival. Blocking TSP1 binding or suppressing CD47 expression drastically increases graft survival. The therapeutic applications of this approach could include burn patients and the broader group of people requiring grafts or tissue flaps for closure and reconstruction of complex wounds of diverse etiologies. Thrombospondin-1 is a potent physiologic regulator of nitric oxide-driven blood flow and angiogenesis. This regulation requires the cell receptor CD47. In a murine model of skin graft survival we demonstrate that endogenous thrombospondin-1 limits graft survival via CD47 and targeting CD47 with antibodies or suppressing CD47 with a morpholino oligonucleotide enhances graft survival by blocking this pathway.
2006-05-01 | Interactions of Systemic Immune Response and Local Wound Healing in Different Burn Depths: An Experimental Study on Rats
This study aimed to clarify the local and systemic immune responses at different burn depths. Thirty female Sprague-Dawley rats were divided into three groups: full-thickness (F), partial-thickness (P), and Sham (S). Burns were induced on three separate areas on the dorsums of rats. Serum levels of interferon (IFN)-gamma; tumor necrosis factor-alpha; interleukin (IL)-1, IL-6, and IL-10 were measured once in controls and 1 hour after burn, 48 hours after burn, and 7 days after burn in F and P groups. Neutrophils, CD68-positive macrophages, HLA-DR-positive cells, and CD3-positive lymphocytes were graded semiquantitatively, and the wounds were examined once in shams and at 1 hour after burn, 48 hours after burn, and 7 days after burn in F and P groups. IL-6 levels were highest in F group, followed by P group 1 hour after burn. IFN-gamma levels were higher in the F group; IL-1 levels were higher in F and P groups at 1 hour after burn. Local accumulation of macrophages was similar in F and P groups. Lymphocytes were denser in P group at 1 hour after burn, and neutrophils were denser in F group at 7 days after burn. We suggest that early elevations of IL-6 and IFN-gamma prolong inflammation in full-thickness burns. Modulation of proinflammatory cytokines may improve burn wound treatment.
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2023-06-09 | Investigating the relationship between transcriptomic markers, and burn wound healing and scarring outcomes
This study identified miRNAs, genes and biological pathways associated with wound healing and scarring in children with burn injuries. The miRNAs and genes which were associated with burn injury, burn severity, and burn scarring could be developed into future tools to predict wound healing and scarring outcomes, or new treatments to enhance burn wound healing.
2022-01-01 | The role of b1 methylation, physiologic replication independent endogenous dna double strand breaks (phy-rind-edsb) and laminin 511 e8 proteins in rat second degree burn wound healing
Background: DNA methylation via short interspersed nuclear element (SINE) small interfering (si)RNA prevents DNA damage and promotes cell proliferation. Furthermore, laminin ?5 ?1 ?1(LM511) is an extracellular structural protein that can support epithelial cell adhesion and migration. Box A of high-mobility group box 1 protein (Box A of HMGB1) is a common nuclear protein in eukaryotic cells that can reduce DNA damage response toward burn injury.
Objective: To investigate whether treatment of burn wounds using B1 siRNA, Box A of HMGB1 and LM511-E8 fragment improved wound closure in a rat second-degree burn wound model.
Methods: �I performed a cross-sectional analytical study using tissue and blood samples from post-burn and healthy patients (n = 23 each) to measure Alu methylation levels and patterns. In in vivo experiments, second-degree burn wounds were introduced on the backs of rats. The rats were then divided into control and experiment groups: a B1 siRNA-treated, Box A of HMGB1 protein and LM511-E8, saline-treated control, and calcium phosphate-nanoparticle-treated control group (n = 1520/group). The wounds were imaged on days 0, 7, 14, 21, and 28 post-injuries. The tissue sections were processed for methylation and histological and immunohistochemical examination and scored based on the overall expression of histone H2AX phosphorylated on serine 139 (?H2AX), 8-hydroxy-2?-deoxyguanosine (8-OHdG), and presence of cytokeratin 10 and 14.
Results: Alu methylation levels were lower in hypertrophic scar tissues than in normal skin (29.4 ? 2.5% vs. 35.6? 3.2%, P = 0.0002). Burn wound closure improved in the B1 siRNA-treated group compared to that in the control group, especially from days 14 to 28 post-injury (P < 0.001). The overall pathological score and degree of B1 methylation in the B1 siRNA-treated group improved at days 1428 days post-injury. The Box A of HMGB1 protein group demonstrated improvement in burn wound closure, starting from day 7th until day 28th after injury (P < 0.001). Furthermore, ?H2AX and 8-OHdG expression in the HMGB1 plasmid-treated group was lower than that in the control group (P < 0.05). The re-epithelialisation in the LM511-E8-treated group was quicker than that of the control group at 728 days post-injury, with the largest improvement observed on days 7 and 14 (P < 0.001). The pathological score of the LM511-E8-treated group was higher than that of the control group at 1428 days post-injury.
Conclusion: These results imply that LM511-E8 fragment, B1 siRNA, and Box A of High-mobility group box 1 protein (Box A of HMGB1) are promising therapeutic options for managing second-degree burns.
2014-02-28 | Response of human skin to esthetic scarification
This study was undertaken to investigate changes in RNA expression in previously healthy adult human skin following thermal injury induced by contact with hot metal that was undertaken as part of esthetic scarification, a body modification practice. Subjects were recruited to have pre-injury skin and serial wound biopsies performed. 4 mm punch biopsies were taken prior to branding and 1 h, 1 week, and 1, 2 and 3 months after injury. RNA was extracted and quality assured prior to the use of a whole-genome based bead array platform to describe expression changes in the samples using the pre-injury skin as a comparator. Analysis of the array data was performed using k-means clustering and a hypergeometric probability distribution without replacement and corrections for multiple comparisons were done. Confirmatory q-PCR was performed. Using a k of 10, several clusters of genes were shown to co-cluster together based on Gene Ontology classification with probabilities unlikely to occur by chance alone. OF particular interest were clusters relating to cell cycle, proteinaceous extracellular matrix and keratinization. Given the consistent expression changes at 1 week following injury in the cell cycle cluster, there is an opportunity to intervene early following burn injury to influence scar development.
2006-06-08 | A Role for the Mitogen-activated Protein Kinase Kinase Kinase 1 in Epithelial Wound Healing
The mitogen-activated protein kinase kinase (MEK) kinase 1 (MEKK1) mediates activin B signals required for eyelid epithelium morphogenesis during mouse fetal development. The present study investigates the role of MEKK1 in epithelial wound healing, another activin-regulated biological process. In a skin wound model, injury markedly stimulates MEKK1 expression and activity, which are in turn required for the expression of genes involved in extracellular matrix (ECM) homeostasis. MEKK1 ablation or down-regulation by interfering RNA significantly delays skin wound closure and impairs activation of Jun NH 2 -terminal kinases, induction of plasminogen activator inhibitor (PAI)-1, and restoration of cell–cell junctions of the wounded epidermis. Conversely, expression of wild-type MEKK1 accelerates reepithelialization of full-thickness skin and corneal debridement wounds by mechanisms involving epithelial cell migration, a cell function that is partially abolished by neutralizing antibodies for PAI-1 and metalloproteinase III. Our data suggest that MEKK1 transmits wound signals, leading to the transcriptional activation of genes involved in ECM homeostasis, epithelial cell migration, and wound reepithelialization.
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Drug Discovery Landscape
19 orphan drug designations for Partial deep dermal and full thickness burns, including 3 approved therapies.
19 orphan drug designations for Partial deep dermal and full thickness burns, including 3 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Human allogeneic keratinocytes | cell therapies | EMA | 2022-06-21 | — | Evomedis GmbH |
Human keratinocytes | cell therapies | EMA | 2021-08-20 | — | Dizg Deutsches Institut Für Zell- Und Gewebeersatz gGmbH |
Genetically engineered (alpha-1,3-galactosyltransferase knock-out}, live cell porcine (Sus scrofa) xenotransplantation skin graft | cell therapies | FDA | 2021-06-14 | — | XenoTherapeutics, Inc. |
bilayer, engineered collagen hydrogel-based skin graft composed of autologous keratinocytes and fibroblasts | cell therapies | FDA | 2016-09-06 | — | Curtiss AG |
cultured skin substitute (CSS) | cell therapies | FDA | 2016-08-22 | — | Regenicin Inc. |
Sodium hypochlorite | small molecules | EMA | 2016-07-14 | — | Hypo-Stream Ltd |
Bilayer engineered collagen hydrogel-based skin graft composed of autologous keratinocytes and fibroblasts | cell therapies | EMA | 2015-12-14 | — | Yes Pharmaceutical Development Services GmbH |
Autologous Engineered Skin Substitute | cell therapies | FDA | 2012-06-01 | — | Amarantus BioScience Holdings, Inc. |
allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen-dsat [StrataGraft] | cell therapies | FDA | 2012-05-21 | 2021-06-15 | Stratatech Corporation, a Mallinckrodt company |
Fibronectin Peptide | peptides | FDA | 2011-06-29 | — | NeoMatrix Therapeutics, Inc. |
N'-(5-chloro-2-hydroxy-3-methylbenzylidene)-2,4-dihydroxybenzhydrazide | small molecules | EMA | 2008-09-22 | — | Creative Antibiotics Sweden AB |
vibriolysin | proteins | FDA | 2006-06-16 | — | BioMarin Pharmaceutical Inc. |
anacaulase-bcbd [NexoBrid] | proteins | FDA | 2003-08-20 | 2024-08-15 | MediWound, Ltd. |
anacaulase-bcdb [NexoBrid] | other | FDA | 2003-08-20 | 2022-12-28 | Vericel Corporation |
Concentrate of proteolytic enzymes enriched in bromelain [NexoBrid] | proteins | EMA | 2002-07-30 | — | MediWound Germany GmbH |
Silver sulfadiazine and cerium nitrate | small molecules | FDA | 1999-11-17 | — | Alliance Pharmaceuticals Ltd |
Ananain, comosain | other | FDA | 1992-01-21 | — | Genzyme Corporation |
Poloxamer 188 | small molecules | FDA | 1990-02-22 | — | CytRx Corporation |
Somatropin (rDNA) | proteins | FDA | 1989-05-03 | — | EMD Serono, Inc. |
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