Application of 3D-printed tissue-engineered skin substitute using innovative biomaterial loaded with human adipose-derived stem cells in wound healing

Large-scale skin injuries often lead to impaired wound healing with scarring, morbidity, or mortality. This study explores in vivo application of a 3D-printed tissue-engineered skin substitute composed of adipose tissue decellularized extracellular matrix (dECM), methacrylated gelatin (GelMA), and methacrylated hyaluronic acid (HAMA), loaded with human adipose-derived stem cells (hADSCs). Adipose tissue was decellularized, lyophilized, solubilized to obtain a thermo-sensitive dECM pre-gel, and blended with GelMA-HAMA to improve printability. Rheology assessed phase-transition behavior; SEM characterized microstructure. A 3D-printed grid-like scaffold encapsulating hADSCs was fabricated and evaluated in a nude mouse full-thickness wound model against three controls: full-thickness skin graft, microskin graft, and untreated wounds. dECM met decellularization criteria (24.5 ± 7.1 ng DNA/mg). The composite precursor underwent a gel–sol transition at ~17.5°C with G'≈G''≈8 Pa; crosslinked hydrogels exhibited porous 3D networks. In vivo, 3D-printed skin substitutes accelerated wound closure, attenuated inflammation, increased local perfusion, enhanced re-epithelialization, collagen deposition and alignment, and promoted angiogenesis. In summary, 3D-printed dECM–GelMA–HAMA skin substitutes loaded with hADSCs can be rapidly fabricated and improve wound healing quality, with hADSCs and the stable printed scaffold both contributing to therapeutic effects.

Huijuan Fu, Dequan Zhang, Jinshi Zeng, Qiang Fu, Zhaoyang Chen, Xuer Sun, Yi Yang, Shiyi Li, Minliang Chen