3D-printed biomimetic scaffold with liposome-encapsulated SB431542 promotes scarless wound healing

Abnormal wound scarring often leads to functional impairments and cosmetic deformities, primarily driven by the prolonged activation of the TGF-β/Smad signaling pathway. Addressing this challenge, we developed a biomimetic scaffold aimed at facilitating rapid and scarless wound healing. This highly integrated 3D-printed dermal scaffold comprised modified recombinant human type III collagen (rhCOLIII-MA), gelatin methacrylate (GelMA), and liposomes encapsulating SB431542 to target TGF-β1 (Lip@SB). The rhCOLIII-MA/GelMA (CG) scaffold retained inherent biomaterial characteristics, exhibited tailored physicochemical properties, and demonstrated favorable biocompatibility. Moreover, the Lip@SB-loaded CG scaffold (CGL) effectively promoted in vitro wound healing, while enabling controlled release of SB431542 to inhibit pathological collagen deposition. In a full-thickness skin defect rat model, the CGL dermal scaffold combined with split-thickness skin graft (STSG) minimized scar contraction, stimulated functional neovascularization, and enhanced graft aesthetics comparable to normal skin. Remarkably, the performance of the CGL scaffold surpassed that of commercially available anti-scarring alternatives. This innovative strategy presents a straightforward approach toward scarless skin regeneration and holds promise in alleviating the prolonged, painful postoperative rehabilitation.