A modified bacterial nanocellulose-based advanced therapy product accelerates third-degree burn healing in murine models

Severe burn injuries represent a major global healthcare burden, with high costs and prolonged hospitalizations. Current treatments, including autologous skin grafting, are limited by donor availability, while allografts carry risks of immune rejection. Advanced Therapy Medicinal Products (ATMPs) offer a promising alternative for skin substitution. We evaluated the efficacy of ARTSkin, an alginate-modified bacterial nanocellulose-based ATMP, in a murine model of third-degree burns. ARTSkin was manufactured under good manufacturing practice (GMP) conditions in two formulations: an acellular scaffold and a cellular construct containing human dermal fibroblasts. The acellular formulation was first assessed in vitro for cytotoxicity and wound-healing capacity using a scratch assay. In vivo, acellular and cellular ARTSkin were evaluated in immunocompetent and immunosuppressed mice, respectively. Acellular ARTSkin was non-cytotoxic and enhanced fibroblast migration and proliferation in vitro. Both formulations significantly improved wound healing in vivo, with accelerated closure and reduced bleeding, hyperemia, edema, and crust formation. Transcriptomic analysis showed that cellular ARTSkin modulated genes involved in the proliferative phase of healing by preventing burn-induced dysregulation of Rac1, Vegfa, and Itga4, and downregulating the profibrotic gene Ctgf. These findings support ARTSkin as a promising skin substitute for burn therapy.