Zhicheng Hu, Hao Yang, Peng Wang, Xiaoling Cao, Peng Wang, Bing Tang, Hailin Xu, Zhiyong Wang, Shaobin Huang, Jian Zhang, Chunli Xue, Qiang Zhou, Xiaohui Li, Honglin Wu, Yi Zhang, Julin Xie, Jiayuan Zhu
Full-thickness wounds remain a major clinical challenge, and tissue-engineered skin using epidermal stem cells (EpiSCs) offers a promising strategy for bio-inspired reconstruction. In this randomized controlled trial, 232 patients with full-thickness defects (≥ 9 cm2) received either standard treatment (acellular dermal matrix [ADM] + split-thickness skin graft [STSG], n = 112) or cell therapy (ADM + STSG + EpiSC suspension, n = 120). Autologous EpiSCs were prepared intraoperatively in a single step, avoiding prolonged in vitro expansion. The primary outcome was 6-month scar quality assessed by the Vancouver Scar Scale (VSS), while secondary outcomes included 2-week healing and 3-month recurrence. Compared with standard treatment, cell therapy produced significantly lower total VSS scores (median 3.0 vs. 6.0, p < 0.001) and improved complete wound healing at 2 weeks (80/120 [66.7%] vs. 61/112 [54.5%]; adjusted odds ratios [OR] = 1.87, 95% confidence interval [CI] 1.06-3.28, p = 0.029). Complete healing at 2 weeks was associated with reduced 3-month recurrence (adjusted OR = 0.26, 95% CI 0.09-0.75, p = 0.012). These findings support intraoperative EpiSC-enhanced composite grafting as an effective and clinically translatable approach for rapid closure and improved long-term scar outcomes.