Photocurable Allyl-Succinylated Collagen Bioink for High-Resolution 3D Bioprinting and Regenerative Diabetic Wound Healing

Abstract

Three-dimensional (3D) bioprinting of collagen-based hydrogels remains limited by poor solubility, weak mechanics, and slow photocrosslinking, which hinder print fidelity and restrict clinical translation. Here, we report a photocurable allyl-succinylated collagen (CAA) bioink that overcomes these long-standing challenges by integrating enhanced molecular solubility, rapid photocrosslinkability, and intrinsic bioactivity. The allyl-succinyl modification markedly improved collagen solubility and enabled efficient radical-mediated polymerization, yielding hydrogels with excellent structural integrity, tunable stiffness, and high-resolution DLP printing performance. In vitro, CAA demonstrates excellent cytocompatibility, promoting cell adhesion, proliferation, migration, and 3D encapsulation with high postprinting viability. In a full-thickness diabetic wound model, bioprinted CAA constructs, especially when combined with fibroblasts and keratinocytes, significantly accelerated wound closure, enhanced collagen I/III regeneration, restored elastic fiber integrity, stimulated angiogenesis, and reduced oxidative stress, collectively restoring ECM homeostasis and tissue architecture. Furthermore, the upregulation of regenerative markers, such as Ki67 and EGF, highlights the material’s ability to modulate the wound microenvironment and activate endogenous repair pathways. This work establishes CAA as a highly soluble, bioactive, and photoprintable collagen platform with strong potential for precision 3D bioprinting and regenerative therapy of chronic diabetic wounds.