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Alopecia areata is the second most common form of hair loss in humans after androgenetic alopecia. Although a variety of animal models for alopecia areata have been described, currently the C3H/HeJ mouse model is the most commonly used and accepted. Spontaneous hair loss occurs in 15%-25% of older mice in which the lesions wax and wane, similar to the human disease, with alopecia being more common and severe in female mice. Full-thickness skin grafts from mice with spontaneous alopecia areata to young, normal-haired, histocompatible mice provide a highly reproducible model with progressive lesions that makes it useful for drug efficacy and mechanism-based studies. As alopecia areata is a cell-mediated autoimmune disease, transfer of cultured lymph node cells from affected mice to unaffected, histocompatible recipients also promotes disease development and provides an alternative, nonsurgical protocol. Protocols are presented to produce these models such that they can be used to study alopecia areata and to develop novel drug therapies. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Full-thickness skin grafts to reproducibly induce alopecia areata in C3H/HeJ mice Basic Protocol 2: Adoptive transfer of cultured lymphoid cells provides a nonsurgical method to induce alopecia areata in C3H/HeJ mice.

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BACKGROUND: Full-thickness skin grafts are widely used in plastic and reconstructive surgery. The main limitation of skin grafting is the poor textural durability and associated contracture, which often needs further corrective surgery. Excessive inflammation is the main reason for skin graft contractions, which involve overactivation of myofibroblasts. These problems have prompted the development of new therapeutic approaches, including macrophage polarization modulation and stem cell-based therapies. Currently, adipose-derived stem cells (ASCs) have shown promise in promoting skin grafts survival and regulating macrophage phenotypes. However, the roles of ASCs on macrophages in decreasing skin grafts contraction remain unknown. MATERIALS AND METHODS: Rat adipose-derived stem cells (rASCs) were isolated from rat inguinal adipose tissues. Full-thickness skin graft model was constructed on male rats divided into control group and rASCs treatment group. Skin graft was assessed for concentration, elasticity modulus and stiffness. Rat bone marrow-derived macrophages (rBMDMs) were isolated from rat femurs, and subsequent RT-qPCR and coculture assays were carried out to explore the cellular mechanisms. Immunohistochemical and immunofluorescence staining were used to verify mechanisms in vivo. RESULTS: In vivo results showed that after injection of ASCs, improved texture, increased survival and inhibited contraction of skin grafts were seen. Vascularization was also improved as illustrated by laser perfusion image and vascular endothelial growth factor (VEGF) concentration. Histological analysis revealed that ASCs injection significantly reduced expression of pro-inflammatory cytokines (TNF-a, IL-1ß) and increased expression of anti-inflammatory (IL-10) and pro-healing cytokines (IGF-1). At cellular level, after co-culturing with rASCs, rat bone marrow derived macrophages (rBMDMs) favored M2 polarization even under inflammatory stimulus. CONCLUSION: ASCs treatment enhanced vascularization via angiogenic cytokines secretion and alleviated inflammatory environment in skin grafts by driving M2 macrophages polarization, which improved survival and decreased skin grafts contraction. Our work showed that ASCs transplantation can be harnessed to enhance therapeutic efficacy of skin grafting in cutaneous defects treatment.

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Investigating the growing concern of pediatric burn injuries caused by social media challenges. Adolescents, seeking fame or succumbing to peer pressure, engage in risky behaviors, recording and sharing them online. The study presents two case reports detailing severe burn injuries resulting from such challenges, highlighting the physical and psychological toll on affected children and their families. In Case report 1, a 14-year-old suffered severe burns attempting a TikTok challenge involving igniting a soaked t-shirt. The patient's critical condition necessitated intensive care, surgical procedures, and skin grafts, accompanied by complications like anemia and sepsis. Case report 2 features a 9-year-old who sustained extensive burns while attempting another social media challenge. Treatment included escharolysis, skin grafts, and surgeries, with complications managed during the recovery process. A literature review explores social media-generated burn injuries, revealing their physical and psychological impact. The influence of social proof and peer pressure on adolescents' behavior in the digital age is discussed. The pandemic's effect on mental health is considered, emphasizing the vulnerability of adolescents to such challenges. In conclusion, the paper highlights the rising incidence of teen burn injuries linked to social media challenges. Urgent measures are needed to restrict the promotion of risky behaviors on social platforms. Alongside state-of-the-art burn treatments, comprehensive psychological care is essential for young patients and their families to cope with trauma. Increased content monitoring and the dissemination of prevention materials are recommended to mitigate the occurrence of such incidents.

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The physical, emotional, and financial toll of acute and chronic nonhealing wounds on older adults and their caregivers is immense. Surgical treatment of wounds in older adults can facilitate healing but must consider the medical complexity of the patient, the patient's desires for treatment and the likelihood of healing. Innovative approaches and devices can promote rapid healing. By using a team approach, from preoperative planning to postoperative care, with a focus on the needs and desires of the patient, successful outcomes with improved patient satisfaction are possible even in medically complex patients.

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Preservation and restoration of hand function after burn injuries are challenging yet imperative. This study aimed to assess the curative effect of a composite skin graft over an acellular dermal matrix (ADM) and a thick split-thickness skin graft (STSG) for treating deep burns on the hand. Patients who met the inclusion criteria at the First Affiliated Hospital of Wenzhou Medical University between September 2011 and January 2020 were retrospectively identified from the operative register. We investigated patient characteristics, time from operation to the start of active motion exercise, take rates of skin graft 7 days post-surgery, donor site recovery, complications and days to complete healing. Patients were followed up for 12 months to evaluate scar quality using the Vancouver Scar Scale (VSS) and hand function through total active motion (TAM) and the Jebsen-Taylor Hand Function Test (JTHFT). A total of 38 patients (52 hands) who received thin STSG on top of the ADM or thick STSG were included. The location of the donor sites was significantly different between Group A (thick STSG) and Group B (thin STSG + ADM) (p = 0.03). There were no statistical differences in age, gender, underlying disease, cause of burn, burn area, dominant hand, patients with two hands operated on and time from burn to surgery between the two groups (p > 0.05). The time from operation to the start of active motion exercise, take rates of skin graft 7 days post-surgery and days to complete healing were not significantly different between Group A and Group B (p > 0.05). The rate of donor sites requiring skin grafting was lower in Group B than in Group A (22.2% vs. 100%, p < 0.001). There were no statistically significant differences in complications between the groups (p = 0.12). Moreover, 12 months postoperatively, the pliability subscore in the VSS was significantly lower in Group A than in Group B (p = 0.01). However, there were no statistically significant differences in vascularity (p = 0.42), pigmentation (p = 0.31) and height subscores (p = 0.13). The TAM and JTHFT results revealed no statistically significant differences between the two groups (p = 0.22 and 0.06, respectively). The ADM combined with thin STSG is a valuable approach for treating deep and extensive hand burns with low donor site morbidity. It has a good appearance and function in patients with hand burns, especially in patients with limited donor sites.

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Post-combustion alopecia presents a complex medical challenge with implications spanning dermatological and psychiatric disorders. The use of hair transplantation has proven to be a significant improvement for this condition. However, the current management involves various techniques, each with advantages and disadvantages. Progressive skin expansions, surgical scar reduction, and skin grafts containing hair follicles yield unsatisfactory aesthetic outcomes and have limited applicability as a first-line treatment for fire victims. So far, follicular unit extraction (FUE) has proven to be one of the most versatile procedures in such cases, having the potential to restore a natural anatomical profile closely resembling the pre-traumatic appearance that led to the traumatic alopecia. Additionally, it contributes to the improvement of associated psychiatric comorbidities, facilitating proper social reintegration and enhancing overall quality of life. This report focuses on a case of post-combustion alopecia and severe facial distortion due to third-degree burns resulting in severe psychiatric comorbidities, which benefited from a proper social reintegration and improvement of the quality of life after three consecutive sessions of FUE for scalp and eyebrow hair.

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The goal for treating pediatric burns is to allow the patient to heal with as little scarring as possible. Compared to older children and adults, very small children have anatomic differences that alter their treatment. They have thinner skin that leads to a higher risk for full-thickness burns. Children also tend to freeze when touching a hot item, so that the prolonged contact also leads to deeper burns. Two healing strategies are needed to treat these wounds. One must optimize reepithelialization in superficial burns to reduce scarring. Deeper burns require skin grafting, but there are techniques, such as the use of "sheet" autograft skin that lead to excellent outcomes. Strategies to treat the massive pediatric burn will also be covered. Finally, there are instances where different strategies are needed to cover exposed bone or tendon. The ultimate goal is to return the skin to as normal a state as possible.

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INTRODUCTION: This study will explore the effectiveness of fish skin grafts (FSG) in ulcer healing in diabetic foot disease compared to standard of care (SOC). METHODS: The systematic review and meta-analysis were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. The electronic databases of PubMed, EMBASE, and Web of Science (WoS) internet were searched for the outcome rate of complete ulcer healing. The risk of bias assessment was conducted using the tool recommended by the Cochrane Collaboration. Statistical analysis included the individual and combined result of the studies, heterogeneity test, the effect size, sensitivity analysis, and publication bias tests. RESULTS: Five randomised controlled trials (RCTs) with a total of 411 patients were included in this study. This meta-analysis showed a higher rate of complete ulcer healing in groups receiving fish skin grafts (OR = 3.34, 95% CI 2.14-5.20, p < 0.01, I2 = 0%) compared to control groups. CONCLUSION: Fish skin grafts have been shown to be more effective for achieving complete ulcer healing compared to current conventional treatments in diabetic foot disease.

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Skin-on-a-chip (SoC) technologies are emerging as a paradigm shift in dermatology research by replicating human physiology in a dynamic manner not achievable by current animal models. Although animal models have contributed to successful clinical trials, their ability to predict human outcomes remains questionable, owing to inherent differences in skin anatomy and immune response. Covering areas including infectious diseases, autoimmune skin conditions, wound healing, drug toxicity, aging, and antiaging, SoC aims to circumvent the inherent disparities created by traditional models. In this paper, we review current SoC technologies, highlighting their potential as an alternative to animal models for a deeper understanding of complex skin conditions.

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This study was carried out to compare the efficacy of vacuum dressing and conventional dressing over split skin grafts in burn patients. It was a single-center prospective cohort study on patients, with less than 40% TBSA burn, undergoing skin grafting at 2 different sites simultaneously over the burn wounds. One site underwent conventional dressing following grafting, and the other underwent vacuum dressing. The primary objective was to compare the percentages of skin graft uptake on Day 5 and Day 14. The secondary objectives were to compare the duration of dressings, time for complete epithelization, need for regrafting, and wound swab culture positivity rates. Three independent examiners assessed the efficacy of dressings in terms of epithelization percentage, need for continued dressing, graft loss, wound swab culture positivity rate, and qualitative assessment of grafts. A total of 16 patients were included in the study. The graft loss, number of days of dressings, and complete epithelization time were statistically lower in the negative-pressure wound therapy (NPWT) group compared with the conventional group (P values .007, .006, and 0009, respectively). The percentage of epithelization was also found to be higher in the NPWT group (P = .006). The incidence of positive cultures and clinically significant graft loss was found to be lower in the NPWT group. However, this was not found to be statistically significant. NPWT dressings can be used in burn wounds following skin grafting and have been found to reduce the time for epithelization compared to conventional dressing.

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Recessive dystrophic epidermolysis bullosa (RDEB) is a rare and severe genetic skin disease responsible for blistering of the skin and mucosa after minor trauma. RDEB is caused by a wide variety of variants in COL7A1 encoding type VII Collagen, the major component of anchoring fibrils that form key attachment structures for dermal-epidermal adherence. In this study, we achieved highly efficient COL7A1 editing in primary RDEB keratinocytes and fibroblasts from 2 patients homozygous for the c.6508C>T (p.Gln2170∗) variant through CRISPR/Cas9-mediated homology-directed repair. Three guide RNAs targeting the c.6508C>T variant or harboring sequences were delivered together with high-fidelity Cas9 as a ribonucleoprotein complex. Among them, one achieved 73% cleavage activity in primary RDEB keratinocytes and RDEB fibroblasts. Then, we treated RDEB keratinocytes and RDEB fibroblasts with this specific ribonucleoprotein complex and the corresponding donor template delivered as single-stranded oligodeoxynucleotide and achieved up to 58% of genetic correction as well as type VII Collagen rescue. Finally, grafting of corrected 3-dimensional skin onto nude mice induced re-expression and normal localization of type VII Collagen as well as anchoring fibril formation at the dermal-epidermal junction 5 and 10 weeks after grafting. With this promising nonviral approach, we achieved therapeutically relevant specific gene editing that could be applicable to all variants in exon 80 of COL7A1 in primary RDEB cells.

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According to the World Health Organization (WHO), around 11 million people suffer from burns every year, and 180,000 die from them. A burn is a condition in which heat, chemical substances, an electrical current or other factors cause tissue damage. Burns mainly affect the skin, but can also affect deeper tissues such as bones or muscles. When burned, the skin loses its main functions, such as protection from the external environment, pathogens, evaporation and heat loss. Depending on the stage of the burn, the patient's condition and the cause of the burn, we need to choose the most appropriate treatment. Personalization and multidisciplinary collaboration are key to the successful management of burn patients. In this comprehensive review, we have collected and discussed the available treatment options, focusing on recent advances in topical treatments, wound cleansing, dressings, skin grafting, nutrition, pain and scar tissue management.

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INTRODUCTION: Burn patients receiving split thickness skin grafting are left with scarring and chronically dysfunctional grafted skin. Given evidence that patients' preoperative expectations mediate postoperative outcomes and satisfaction, we described burn patients' experience, expectations, and satisfaction with their skin graft, their views towards a cell based clinical trial to improve their graft and identified graft outcome measures for use in future studies. METHODS: Data were collected via questionnaires preoperatively, one, and three months postoperatively. Longitudinal analyses assessed change over time. RESULTS: Expectations of graft function were consistent pre- and postoperatively. Expectations of graft appearance showed significant decrease over time (ß1 = -0.290, p = 0.008). Significant improvements in skin function (ß1 = 0.579, p = 0.000) and appearance (ß1 = 0.247, p = 0.025) at the wound site during recovery were observed. Patients noted great difference between grafted and normal skin. Patient satisfaction with their graft did not change significantly over time. Patients were willing to participate in a cell based clinical trial to improve graft symptomology and prioritized improvements in scarring, redness, sensation, and elasticity. CONCLUSIONS: Outcome measures in trials advancing skin grafting should reflect chronic, patient prioritized limitations. We recommend preoperative educational interventions for burn patients receiving grafting to improve postoperative satisfaction.

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BACKGROUND: Necrotizing fasciitis (NF) is a serious infectious disease that can initially place the patient's life in danger and, after successful surgical and antibiotic treatment, leaves extensive wounds with sometimes even exposed bones and tendons. Autologous skin grafts are not always possible or require adequate wound bed preparation. Novel intact fish skin grafts (iFSGs; Kerecis® Omega3 Wound, Kerecis hf, Isafjördur, Iceland) have already shown their potential to promote granulation in many other wound situations. Faster wound healing rates and better functional and cosmetic outcomes were observed due to their additionally postulated anti-inflammatory and analgesic properties. Therefore, iFSGs may also be essential in treating NF. We present our initial experience with iFSGs in treating leg wounds after NF and review the literature for the current spectrum of clinical use of iFSGs. CASE PRESENTATIONS: We present two male patients (aged 60 and 69 years) with chronic or acute postsurgical extensive leg ulcers six weeks and six days after necrotizing fasciitis, respectively. Both suffered from diabetes mellitus without vascular pathologies of the lower limbs. A single application of one pre-meshed (Kerecis® Graftguide) and one self-meshed 300 cm2 iFSG (Kerecis® Surgiclose) was performed in our operation room after extensive surgical debridement and single circles of negative wound pressure therapy. Application and handling were easy. An excellent wound granulation was observed, even in uncovered tibia bone and tendons, accompanied by pain relief in both patients. Neither complications nor allergic reactions occurred. The patients received autologous skin grafting with excellent functional and cosmetic outcomes. CONCLUSIONS: iFSGs have the potential to play a significant role in the future treatment of NF due to the fast promotion of wound granulation and pain relief. Our experience may encourage surgeons to use iFSGs in NF patients, although high-quality, large-sized studies are still required to confirm these results. The observed effects of iFSGs on wounds associated with NF may be transferred to other wound etiologies as well.

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Autologous cell therapy manufacturing timeframes constitute bottlenecks in clinical management pathways of severe burn patients. While effective temporary wound coverings exist for high-TBSA burns, any means to shorten the time-to-treatment with cytotherapeutic skin grafts could provide substantial therapeutic benefits. This study aimed to establish proofs-of-concept for a novel combinational cytotherapeutic construct (autologous/allogeneic DE-FE002-SK2 full dermo-epidermal graft) designed for significant cutaneous cell therapy manufacturing timeframe rationalization. Process development was based on several decades (four for autologous protocols, three for allogeneic protocols) of in-house clinical experience in cutaneous cytotherapies. Clinical grade dermal progenitor fibroblasts (standardized FE002-SK2 cell source) were used as off-the-freezer substrates in novel autologous/allogeneic dermo-epidermal bilayer sheets. Under vitamin C stimulation, FE002-SK2 primary progenitor fibroblasts rapidly produced robust allogeneic dermal templates, allowing patient keratinocyte attachment in co-culture. Notably, FE002-SK2 primary progenitor fibroblasts significantly outperformed patient fibroblasts for collagen deposition. An ex vivo de-epidermalized dermis model was used to demonstrate the efficient DE-FE002-SK2 construct bio-adhesion properties. Importantly, the presented DE-FE002-SK2 manufacturing process decreased clinical lot production timeframes from 6-8 weeks (standard autologous combined cytotherapies) to 2-3 weeks. Overall, these findings bear the potential to significantly optimize burn patient clinical pathways (for rapid wound closure and enhanced tissue healing quality) by combining extensively clinically proven cutaneous cell-based technologies.

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BACKGROUND: Pressure ulcers remain a worldwide problem. OBJECTIVE: To introduce an intermittent and feasible wound treatment method for the treatment of pressure ulcers in elderly patients. METHODS: This surgical procedure was performed on eight elderly patients suffering from pressure ulcers. Microskin measuring 0.1 × 0.1 centimeters was cut from a small amount of thin skin and then grafted onto the wound surface in conjunction with closed negative pressure therapy. RESULTS: Seven patients had their wounds closed after a single surgery, while one patient required two surgeries to close the wound. CONCLUSION: Autologous microskin implantation for the treatment of pressure ulcers in the elderly is an effective method to close the wound, which can prevent the elderly from living with wounds in their later years and is a viable treatment option.

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Chronic wounds such as diabetic foot ulcers and venous leg ulcers place a significant burden on the healthcare system and in some cases, have 5-year mortality rates comparable to cancer. They negatively impact patients' quality of life due to pain, odor, decreased mobility, and social isolation. Skin substitutes are an advanced therapy recommended for wounds that fail to show decrease in size with standard care. The choice of substitute used should be based on evidence, which often differs based on wound etiology. There are more than 75 skin substitutes currently available, and that number is rising. In this review, we discuss current management and future directions of chronic wounds while providing a review of available randomized control trial data for various skin substitutes.