DLP Bioprinting of Bilayer Recombinant Collagen Scaffolds for Immunoangiogenic Microenvironment Remodeling and Diabetic Wound Regeneration.

Abstract

Chronic diabetic wounds remain difficult to heal because of persistent oxidative stress, chronic inflammation, impaired angiogenesis, and dysfunctional extracellular matrix remodeling. Developing biofabricated living scaffolds that combine structural support with active microenvironment regulation remains challenging. Herein, we engineered a photocrosslinkable methacrylated recombinant type I collagen bioink (RCIMA) and fabricated a biomimetic bilayer cell-laden scaffold (RCIMA-Cell) using digital light processing (DLP) bioprinting. Owing to the excellent physiological processability of recombinant collagen, RCIMA exhibited rapid photocuring, enhanced swelling behavior, improved enzymatic stability, and superior mechanical performance. The bilayer scaffold spatially integrated keratinocytes (HaCaT) and fibroblasts (HFF-1) to mimic the hierarchical architecture of native skin. In vitro, RCIMA promoted the migration, proliferation, and differentiation of both cell types while maintaining high post-printing viability. In diabetic wounds, RCIMA-Cell accelerated wound closure, promoted collagen remodeling, reduced ROS accumulation, induced M2 macrophage polarization, and enhanced angiogenesis and vascular maturation, offering a versatile strategy for regenerative wound repair.