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Slough is a well‐known feature of non‐healing wounds. This pilot study aims to determine the proteomic and microbiologic components of slough as well as interrogate the associations between wound slough components and wound healing. Ten subjects with slow‐to‐heal wounds and visible slough were enrolled. Aetiologies included venous stasis ulcers, post‐surgical site infections and pressure ulcers. Patient co‐morbidities and wound healing outcome at 3‐months post‐sample collection was recorded. Debrided slough was analysed microscopically, through untargeted proteomics, and high‐throughput bacterial 16S‐ribosomal gene sequencing. Microscopic imaging revealed wound slough to be amorphous in structure and highly variable. 16S‐profiling found slough microbial communities to associate with wound aetiology and location on the body. Across all subjects, slough largely consisted of proteins involved in skin structure and formation, blood‐clot formation and immune processes. To predict variables associated with wound healing, protein, microbial and clinical datasets were integrated into a supervised discriminant analysis. This analysis revealed that healing wounds were enriched for proteins involved in skin barrier development and negative regulation of immune responses. While wounds that deteriorated over time started off with a higher baseline Bates‐Jensen Wound Assessment Score and were enriched for anaerobic bacterial taxa and chronic inflammatory proteins. To our knowledge, this is the first study to integrate clinical, microbiome, and proteomic data to systematically characterise wound slough and integrate it into a single assessment to predict wound healing outcome. Collectively, our findings underscore how slough components can help identify wounds at risk of continued impaired healing and serves as an underutilised biomarker. [ABSTRACT FROM AUTHOR]

Key points: Several distinct strategies produce and conserve heat to maintain the body temperature of mammals, each associated with unique physiologies, with consequences for wellness and disease susceptibilityHighly regulated properties of skin offset the total requirement for heat production We hypothesize that the adipose component of skin is primarily responsible for modulating heat flux; here we evaluate the relative regulation of adipose depots in mouse and human, to test their recruitment to heat production and conservationWe found that insulating mouse dermal white adipose tissue accumulates in response to environmentally and genetically induced cool stress; this layer is one of two adipose depots closely apposed to mouse skin, where the subcutaneous mammary gland fat pads are actively recruited to heat productionIn contrast, the body‐wide adipose depot associated with human skin produces heat directly, potentially creating an alternative to the centrally regulated brown adipose tissue Mammalian skin impacts metabolic efficiency system‐wide, controlling the rate of heat loss and consequent heat production. Here we compare the unique fat depots associated with mouse and human skin, to determine whether they have corresponding functions and regulation. For humans, we assay a skin‐associated fat (SAF) body‐wide depot to distinguish it from the subcutaneous fat pads characteristic of the abdomen and upper limbs. We show that the thickness of SAF is not related to general adiposity; it is much thicker (1.6‐fold) in women than men, and highly subject‐specific. We used molecular and cellular assays of β‐adrenergic‐induced lipolysis and found that dermal white adipose tissue (dWAT) in mice is resistant to lipolysis; in contrast, the body‐wide human SAF depot becomes lipolytic, generating heat in response to β‐adrenergic stimulation. In mice challenged to make more heat to maintain body temperature (either environmentally or genetically), there is a compensatory increase in thickness of dWAT: a corresponding β‐adrenergic stimulation of human skin adipose (in vivo or in explant) depletes adipocyte lipid content. We summarize the regulation of skin‐associated adipocytes by age, sex and adiposity, for both species. We conclude that the body‐wide dWAT depot of mice shows unique regulation that enables it to be deployed for heat preservation; combined with the actively lipolytic subcutaneous mammary fat pads they enable thermal defence. The adipose tissue that covers human subjects produces heat directly, providing an alternative to the brown adipose tissues. [ABSTRACT FROM AUTHOR]

Background: A phase 3b, open-label, multicenter, expanded-access study (NCT04123548) evaluated safety and clinical outcomes of StrataGraft treatment in adults with deep partial-thickness thermal burns with intact dermal elements., Methods: Adult patients with 3 % to < 50 % total body surface area burns were treated with a single application of ≤ 1:1 meshed StrataGraft and followed for 24 weeks. Primary endpoint was count and percentage of patients with treatment-emergent adverse events (TEAEs). Secondary endpoints included confirmed wound closure (WC) at Week 12, durable WC at Week 24, time to WC, scar evaluation, and wound infection-related events., Results: Fifty-two patients with 96 treatment sites were enrolled. Pruritus was the most common TEAE (22 patients [42.3 %]). Twenty serious TEAEs occurred in 10 patients (19.2 %); none were related to StrataGraft. There were 4 (7.7 %) deaths (aspiration, myocardial infarction, self-injury, Gram-negative rod sepsis); none were related to StrataGraft. Confirmed WC was achieved by Week 12 in 33 patients (63.5 %; 95 % CI: 50.4-76.5 %) and 69 treatment sites (71.9 %; 95 % CI: 62.9-80.9 %). Durable WC was achieved by Week 24 in 29 patients (55.8 %; 95 % CI: 42.3-69.3 %) and 58 treatment sites (60.4 %; 95 % CI: 50.6-70.2 %)., Conclusions: StrataGraft demonstrated clinical benefit. Safety data were consistent with previously reported findings., Competing Interests: Declaration of Competing Interest James H. Holmes IV: Equity positions in Abbott Labs, AbbVie, Change Healthcare Inc, and Imbed Biosciences. Consultant for Avita Medical and has received research support from Avita Medical, Mallinckrodt Pharmaceuticals/Stratatech, SpectralMD, and Keranetics. Jeffrey W. Shupp: Research funding from Mallinckrodt Pharmaceuticals, Avita Medical, Urgo Medical, ACell, and Kerecis. JWS has been a consultant for Integra LifeSciences and Avita Medical. Tracee Short: Participated in the clinical advisory boards for Avita Medical, Mallinckrodt Pharmaceuticals, Synergy Biologics, Polynovo, and KCI. Victor C. Joe: Participated in a Mallinckrodt Pharmaceuticals Advisory Board relating to StrataGraft. Jeffrey Litt: Participated in the speaker bureau for Acelity/3AM (ended) and advisory board for Vericel (ended). Joshua Carson: Received research funding from Mallinckrodt Pharmaceuticals and the Biomedical Research and Development Authority (BARDA) and personal fees from Integra LifeSciences, Avita Medical, and Mallinckrodt Pharmaceuticals. Jeffrey E. Carter: Equity positions in PermeaDerm, Inc and is a consultant for Avita Medical. Research support from Avita Medical, SpectralMD, and Keranetics. Lucy Wibbenmeyer: Received research funding from Mallinckrodt Pharmaceuticals, Mediwound, and Biomedical Research and Development Authority (BARDA) and consultant fees from Vericel, Allosource, and Mallinckrodt Pharmaceuticals. Helen Hahn: Previous employee of Mallinckrodt Pharmaceuticals. Janice M. Smiell: Previous employee of Mallinckrodt Pharmaceuticals. Randi Rutan: Previous employee of Mallinckrodt Pharmaceuticals. Richard Wu: Employee of Mallinckrodt Pharmaceuticals. Angela L. F. Gibson: Received grant/research support from Mallinckrodt Pharmaceuticals., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: The authors report no conflicts of interest.

Neutrophils accumulate early in tissue injury. However, the cellular and functional heterogeneity of neutrophils during homeostasis and in response to tissue damage remains unclear. In this study, we use larval zebrafish to understand neutrophil responses to thermal injury. Single-cell transcriptional mapping of myeloid cells during a 3-d time course in burn and control larvae revealed distinct neutrophil subsets and their cell-cell interactions with macrophages across time and conditions. The trajectory formed by three zebrafish neutrophil subsets resembles human neutrophil maturation, with varying transition patterns between conditions. Through ligand-receptor cell-cell interaction analysis, we found that neutrophils communicate more in burns in a pathway and temporal manner. Finally, we identified the correlation between zebrafish myeloid signatures and human burn severity, establishing GPR84+ neutrophils as a potential marker of early innate immune response in burns. This work builds a comparative single-cell transcriptomic framework to identify neutrophil markers of tissue damage using model organisms., (Copyright © 2024 by The American Association of Immunologists, Inc.)

The skin and its microbiome function to protect the host from pathogen colonization and environmental stressors. In this study, using the Wisconsin Miniature Swine™ model, we characterize the porcine skin fungal and bacterial microbiomes, identify bacterial isolates displaying antifungal activity, and use whole-genome sequencing to identify biosynthetic gene clusters encoding for secondary metabolites that may be responsible for the antagonistic effects on fungi. Through this comprehensive approach of paired microbiome sequencing with culturomics, we report the discovery of novel species of Corynebacterium and Rothia. Further, this study represents the first comprehensive evaluation of the porcine skin mycobiome and the evaluation of bacterial-fungal interactions on this surface. Several diverse bacterial isolates exhibit potent antifungal properties against opportunistic fungal pathogens in vitro. Genomic analysis of inhibitory species revealed a diverse repertoire of uncharacterized biosynthetic gene clusters suggesting a reservoir of novel chemical and biological diversity. Collectively, the porcine skin microbiome represents a potential unique source of novel antifungals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: This analysis includes pooled safety data from 2 clinical trials (NCT01437852; NCT03005106) that evaluated the safety and efficacy of StrataGraft in patients with deep partial-thickness (DPT) burns., Methods: The study enrolled 101 adult patients with thermal burns covering 3-49% of total body surface area. Patients were followed for up to 1 year. The pooled safety events included: adverse events (AEs), adverse reactions (ARs), serious AEs (SAEs), discontinuation, and deaths; immunological responses (reactivity to panel reactive antibodies [PRA] and human leukocyte antigen [HLA] class 1 alleles); and persistence of allogeneic DNA from StrataGraft., Results: Eighty-seven (86.1%) patients experienced 397 AEs. Thirty patients (29.7%) experienced ARs; 16 patients (15.8%) experienced SAEs. The most frequent AEs were pruritus (n = 31; 30.7%), and blister, hypertension, and hypertrophic scar (n = 11 each; 10.9%); the most common AR was pruritus (n = 13; 12.9%). One patient discontinued the study; 2 patients experienced SAEs (unrelated to StrataGraft) leading to death. PRA and HLA allele reactivity was ≤ 25% at Month 3, with no persistent allogeneic DNA from StrataGraft., Conclusions: StrataGraft was well tolerated by patients, with a safety profile similar to autograft. StrataGraft may offer a safe alternative to autograft for DPT burns., Competing Interests: Conflicts of interest JHH has equity ownership in Abbott Labs, AbbVie, Imbed Biosciences, and Change Healthcare. JHH is a consultant to Avita Medical and Stratatech and Mallinckrodt Pharmaceuticals plc, Hampton, NJ. LCC, LDF, and BTK have nothing to disclose. JEC has equity positions in PermeaDerm, Inc, and is a consultant for Avita Medical. Research support from Avita Medical, SpectralMD, and Keranetics. KF has been involved in clinical studies for the American Burn Association, Atox-Bio, BARDA, Baxter, Polynovo Biomaterials, Mallinckrodt Pharmaceuticals, Integra LifeSciences, MediWound, MiMedx, Skingenix, Propanolol, Avita Medical, The Canadian Institutes of Health, and Stratatech, all outside the submitted work. HDH, RR, JMS, and RW are employees and shareholders of Mallinckrodt Pharmaceuticals. ALFG is a consultant to Mallinckrodt Pharmaceuticals and Stratatech, a Mallinckrodt company., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)