Light-assisted 3D bioprinting of tough hydrogels in biomedical applications

Light-assisted 3D-bioprinted hydrogels are at the forefront of tissue engineering and biomedical manufacturing due to their precise spatiotemporal controllability and tunable physicochemical properties. However, the mechanical requirements of target organ tissue pose challenges to 3D-bioprinted bio-functional tissue, which must balances biocompatibility, printability, and mechanical strength to replicate the native regenerative microenvironments for functional restoration. This review explores photosensitive polymers with bond chemistry for strengthening hydrogel-based tissue constructs, offering an examination of their potential for facilitating tissue reconstruction through light-assisted 3D bioprinting techniques. We compare the cross-linking chemistry, bond energetics, and resulting mechanics of natural and synthetic hydrogels. Additionally, various light-assisted 3D bioprinting methods for tough hydrogels and engineered living systems are summarized and compared in terms of their practical applications. Importantly, we highlight the critical challenge of enhancing mechanical toughness while balancing the printability, toughness, and biocompatibility of hydrogels via the use of covalent bonds, dynamic covalent bonds, reversible non-covalent interactions, and hybrid bond networks. Furthermore, we discuss emerging applications of light-printed tough hydrogel scaffolds in regenerative medicine and in cartilage, bone, tendon, skull, musculoskeletal, and dental applications. Future prospects and challenges associated with methods of toughing 3D-bioprinted hydrogels are also discussed for guiding future biomedical engineering efforts.