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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.)

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.)

Objective: This phase 3 study evaluated StrataGraft construct as a donor-site sparing alternative to autograft in patients with deep partial-thickness (DPT) burns., Methods: Patients aged ≥18 years with 3-49% total body surface area (TBSA) thermal burns were enrolled. In each patient, 2 DPT areas (≤2000cm 2 total) of comparable depth after excision were randomized to either cryopreserved StrataGraft or autograft. Coprimary endpoints were: the difference in percent area of StrataGraft treatment site and autograft treatment site autografted at Month 3 (M3), and the proportion of patients achieving durable wound closure of the StrataGraft site without autograft at M3. Safety assessments were performed in all patients. Efficacy and safety follow-up continued to 1 year., Results: Seventy-one patients were enrolled. By M3, there was a 96% reduction in mean percent area of StrataGraft treatment sites that required autografting, compared with autograft treatment sites (4.3% vs 102.1%, respectively; P<.0001). StrataGraft treatment resulted in durable wound closure at M3 without autografting in 92% (95% CI: 85.6, 98.8; n/n 59/64) of patients for whom data were available. The most common StrataGraft-related adverse event was pruritus (15%)., Conclusions: Both coprimary endpoints were achieved. StrataGraft may offer a new treatment for DPT burns to reduce the need for autografting., Clinical Trial Identifier: NCT03005106., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Reducing the amount of donor skin needed for definitive wound closure can improve outcomes in patients with severe burns. This Delphi Consensus Panel (DCP) aimed to achieve expert consensus on the percentage reduction in donor skin for autograft that constitutes a clinically meaningful benefit. A two-round DCP of fifteen US burn surgeons was conducted via a web-based survey platform. Fourteen panelists (93.3%) completed both rounds. In Round 2, consensus, defined as ≥70% agreement, was achieved for five of the seven consensus statements. All panelists agreed that a clinically meaningful reduction in the amount of donor skin required would facilitate wound management and decrease donor site morbidity experienced by patients. Furthermore, based on three treatment scenarios, consensus was achieved for a clinically meaningful reduction in the amount of donor skin required for autograft for the adult population in deep partial-thickness and full-thickness burns. Findings from this DCP indicate that an innovative cellular and/or tissue product that would reduce the needed amount of donor skin, by the identified thresholds, has the potential to improve the outcomes for patients with severe burn injuries in a meaningful way., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Early mechanisms underlying the progressive tissue death and the regenerative capability of burn wounds are understudied in human skin. A clinically relevant, reproducible model for human burn wound healing is needed to elucidate the early changes in the human burn wound environment. This study reports a reproducible contact burn model on human skin that explores the extent of tissue injury and healing over time, and defines the inter-individual variability in human skin to enable use in mechanistic studies on burn wound progression and healing., Methods: Using a customized burn device, contact burns of various depths were created on human skin by two operators and were evaluated for histologic depth by three raters to determine reproducibility. Early burn wound progression and wound healing were also evaluated histologically after the thermally injured human skin was cultured ex vivo for up to 14 days., Results: Burn depths were reproducibly generated on human skin in a temperature- or time-dependent manner. No significant difference in operator-created or rater-determined depth was observed within each patient sample. However, significant inter-individual variation was identified in burn depth in ten patient samples. Burn-injured ex vivo human skin placed into culture demonstrated differential progression of cell death and collagen denaturation for high and low temperature contact burns, while re-epithelialization was observed in superficial burn wounds over a period of 14 days., Conclusion: This model represents an invaluable tool to evaluate the inter-individual variability in early burn wound progression and wound healing to complement current animal models and enhance the translation of preclinical research to improvements in patient care., (Copyright © 2020 Elsevier Ltd and ISBI. All rights reserved.)

Objective: This open-label, controlled, randomized study assessed the safety, tolerability, and efficacy of StrataGraft tissue compared to autograft in the treatment of deep partial-thickness (DPT) burns., Methods: Thirty subjects with DPT thermal burns (3%-43% total body surface area) were treated with StrataGraft tissue as follows: cohort 1, ≤220 cm 2 refrigerated tissue; cohort 2, ≤440 cm 2 refrigerated tissue; and cohort 3, ≤440 cm 2 cryopreserved tissue. On each subject, two comparable areas of DPT burn were randomized to receive StrataGraft tissue or autograft. Coprimary end points were the percent area of the StrataGraft tissue treatment site undergoing salvage autografting by Day 28 and wound closure of treatment sites by 3 months., Results: By Day 28, no StrataGraft tissue treatment sites underwent autografting. By 3 months, 93% and 100% of the StrataGraft tissue and autograft treatment sites achieved complete wound closure, respectively. No significant differences in observer total and overall opinion POSAS scores between StrataGraft tissue and autograft treatment sites were observed at any timepoint. The most common adverse event was pruritus (17%)., Conclusions: StrataGraft tissue treatment of DPT thermal burns reduced the need for autograft, resulted in wound closure and treatment-site cosmesis comparable to that of autograft, and was well tolerated., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)