Bioengineered Skin Grafts from Patient‐Derived Decellularized Extracellular Matrix and Autologous Cells for Personalized Regenerative

The skin, as the body's largest organ, plays vital protective and regulatory roles, making it a key target in regenerative medicine. However, current skin models often lack patient specificity and fail to recapitulate native extracellular matrix (ECM) composition, limiting their clinical relevance. This study presents a 3D-bioprinted skin model using a patient-derived decellularized ECM (pddECM) bioink combined with keratin-alginate (KA) bioink, mimicking native skin architecture and function. The pddECM supports high viability of human dermal fibroblasts (HDFs), promoting collagen I production and robust ECM remodeling, while the KA bioink enhances basal keratinocyte activation and cornification. The construct exhibits improved cell migration and angiogenesis, contributing to effective tissue integration and reduced hypoxic stress. Cytokine profiling reveals upregulation of ICAM-1 and complement C5, which are associated with enhanced keratinocyte motility and rapid matrix remodeling, while downregulation of pro-inflammatory cytokines (IL-4 and IL-8) suggests a favorable, fibrosis-suppressive environment. In vivo, GelMA and GelMA+pddECM scaffolds accelerated wound closure without local or systemic toxicity, preserving dermal thickness and inducing migrating epidermal tongue (MET) expression. This patient-specific, bioactive skin model holds strong potential as a next-generation platform for personalized wound healing, drug screening, and high-fidelity skin grafting in translational tissue engineering.