Highly printable and multifunctional cell-laden collagen-based bioinks for precise DLP bioprinting and rapid diabetic wound regeneration

Digital light processing (DLP) bioprinting has revolutionized tissue engineering by offering unprecedented speed and precision. However, its full biomedical potential is hindered by the scarcity of cell-laden bioinks that combine excellent printability with superior bioactivity. In this study, we introduce a novel cell-laden collagen-based bioink optimized for precise DLP bioprinting and diabetic wound regeneration. This bioink integrates methacrylated collagen (CMA) with dihydromyricetin (DHM) and selected additives, achieving a combination of low concentration, high printability, and superior cell bioactivity, along with antioxidant and anti-inflammatory effects. By employing a multi-crosslinking strategy that integrates free radical polymerization, Michael addition, Schiff base formation, and hydrogen bonding, the bioink achieves an ultra-fast gelation speed (375 % increase), a 161 % increase in stiffness, a 231 % improvement in mechanical resilience, and a 208 % enhancement in anti-biodegradation. These properties allow for the fabrication of intricate, cell-laden constructs with micron-scale precision, high cell viability, minimal swelling, and enhanced structural stability. The CMA-DHM system synergistically enhances 3D cell proliferation, mitigates oxidative stress, and modulates macrophage polarization, significantly outperforming conventional CMA hydrogels. Leveraging these properties, we developed biomimetic skin substitutes encapsulating human dermal fibroblasts (HDFs), which effectively facilitate diabetic wound progression through critical healing phases. These skin substitutes provide potent antioxidant and anti-inflammatory effects, accelerate re-epithelialization and collagen deposition, and enhance angiogenesis, thereby preventing chronic wound formation and facilitating efficient tissue regeneration. This study establishes a versatile, scalable DLP bioprinting platform, offering a rapid and effective solution for chronic wound treatment, representing a significant advancement in regenerative medicine.