EClinicalMedicine. 2025 Nov 28;90:103665. doi: 10.1016/j.eclinm.2025.103665. eCollection 2025 Dec.
ABSTRACT
BACKGROUND: For burn surgery, major therapeutic challenges are shortage of autologous donor sites for split-thickness skin, and massive devastating scarring. We investigated the therapeutic role of denovoSkin™, a bio-engineered autologous skin, in a prospective, randomized, controlled phase IIb clinical trial compared to the gold standard the split thickness skin graft (STSG).
METHODS: Patients, ≥12 years, with deep partial and/or full-thickness burns requiring surgical wound coverage were enrolled at four sites in Switzerland, the Netherlands, and Italy. Two comparable skin defects (max. 98 cm2 each) per patient were intra-patient randomized to denovoSkin™ (experimental) or autologous STSG (control) treatment. Safety assessments were performed in all patients. Primary efficacy endpoint was the ratio of biopsy size to grafted area with take 4 weeks post-grafting. The analyses of the primary efficacy variable were performed on the modified Full Analysis Set (mFAS) and the per protocol set (PPS) with the analysis on the mFAS as the primary analysis. Other efficacy endpoints included wound closure and scar quality. Efficacy and safety follow-ups were conducted up to 12 months post-grafting. The trial started in March 2018 and completed recruitment in July 2022 and is registered at clinicaltrials.gov (NCT03227146).
FINDINGS: 21 patients were enrolled between March 26, 2018, and July 26 2022. 13 patients were included in the PPS. There were no significant safety differences between denovoSkin™ and STSG. 164 serious adverse events were observed (81%). Only two (hematoma and partial skin necrosis) could be related to denovoSkin™. They rapidly healed spontaneously. The expansion ratio for denovoSkin™ versus STSG was 7·0 times larger for denovoSkin™ (p < 0·001). In the mFAS the mean expansion ratio for denovoSkin™ was 10·76 (SD 6·03), and for STSG it was 1·70 (SD 0·68). The mean ratio of the two expansion ratios (denovoSkin™/STSG) was 7·41 (SD 4·87). By month 3, experimental and control areas were fully epithelialized. Scar evaluation up to 12 months post-grafting revealed no clinically relevant scarring for denovoSkin™, but mostly hypertrophic scarring for STSG.
INTERPRETATION: DenovoSkin™ is a novel and safe treatment option for deep burns. It lessens the need for conventional grafting and so spares donor sites. In sharp contrast to STSG, denovoSkin™ grafting showed minimal scarring, a finding never evidenced before in a randomized trial.
FUNDING: This study was financed by Wyss Zurich Translational Center (project "denovoSkin") and CUTISS AG.
PMID:41399471 | PMC:PMC12702297 | DOI:10.1016/j.eclinm.2025.103665