Methacrylic anhydride-assisted one-step in-situ extrusion 3D bioprinting of collagen hydrogels for enhanced full-thickness skin regeneration

Abstract

Full-thickness skin injuries cause extended inflammation, compromised angiogenesis, and protracted wound healing, presenting considerable health risks. Herein, we introduce an innovative technique utilizing methacrylic anhydride (MA)-enhanced, one-step in-situ extrusion 3D bioprinting of collagen hydrogels, specifically engineered for the effective repair of full-thickness skin injuries. This method capitalizes on the inherent bioactivity of collagen, surmounting its mechanical constraints via a streamlined, one-step extrusion process enabled by MA. The resultant biomaterial ink, an optimized mix of collagen, MA, and photoinitiator, demonstrates superior printability, mechanical robustness, and stability, making it an ideal candidate for direct application onto wound sites. The bioprinted collagen scaffolds exhibit improved mechanical strength, reduced swelling, and enhanced resistance to enzymatic degradation, providing a durable matrix for cell proliferation and tissue in-growth. In vitro assessments reveal that the scaffolds support human foreskin fibroblast adhesion, proliferation, and migration, creating a conducive environment for skin regeneration. In vivo evaluations, conducted using a rat full-thickness skin injury model, further validate the scaffold's efficacy in promoting rapid and orderly tissue repair, characterized by accelerated re-epithelialization and organized collagen deposition. This MA-enhanced, in-situ extrusion 3D bioprinting technique generates collagen hydrogel scaffolds that significantly accelerate wound healing, offering promising advancements in tissue engineering and regenerative medicine.