Hydrogel-based bioinks for 3D bioprinting articular cartilage: A comprehensive review with focus on mechanical reinforcement

Articular cartilage defects always progress to degenerative osteoarthritis (OA) and negatively affect the quality of life for millions of people globally. Biofabrication technologies have provided strategies for personalized regenerative therapies. Specifically, three-dimensional (3D) printing enables the manufacturing of biomimetic and functional microarchitectures of native tissues, which has become a promising approach for cartilage tissue engineering. Regarding 3D bioprinting, bioinks with excellent biocompatibility, printability, and tunable me-chanical strength play a crucial role in constructing 3D-printed cartilage scaffolds. Hydrogel-based bioinks with crosslinked polymer networks can mimic the native tissue extracellular matrix, and can be designed to print anatomically shaped native tissue, which have been recommended as advanced bioinks to bioprint numerous composite materials to fulfil patient-specific demands. In this review, we summarized the current trends for articular cartilage tissue engineering, and the requirements of bioinks and 3D printing for bioprinting applica-tions. An overview of bioink materials, including the natural polymers and synthetic polymers used for 3D printing articular cartilage, is discussed elaborately. Furthermore, this review also focuses on the current stra-tegies adopted to enhance the mechanical properties of bioinks, including polymer functionalization, formation of interpenetrating polymer networks (IPNs), combination with thermoplastic scaffolds and incorporation of nanomaterials. Finally, it also outlines the future perspectives of bioink reinforcement for 3D bioprinting articular cartilage.