Design, printing, and engineering of regenerative biomaterials for personalized bone healthcare

Trauma- and disease-related skeletal defects and illnesses are plaguing millions of people especially in an ageing globe. Recently, the convergence of additive manufacturing (AM) and bone tissue engineering (BTE) has opened up an era of "Personalized Bone Healthcare", wherein "design", "printing", and "engineering" inputs are judiciously orchestrated to yield custom 3D architected (bio)scaffolds, per relevant AM paradigms, to address biological/pathological complexities of host tissues. In this review, a systematic overview of fundamental theories, recent advances, and future trends in this domain is provided. It starts with a general introduction to BTE and AM, followed by emergent topics, including: (i) the design and choices of biomaterials or bioinks for AM paradigms including acellular 3D printing, 3D bioprinting, 4D (bio)printing, and hierarchical printing; (ii) the utilization of computational tools, design-property relationships, and emerging metamaterial strategies to afford predictive, bionic or smart scaffold geometries; and (iii) the engineering of AM systems, processes, and printed parts, by hardware modification, technology fusion, or material functionalization. The ultimate goal is to produce (bio)scaffolds with customized/biomimetic form (geometry, hierarchy, heterogeneity, cellular microenvironments, etc.) and function. Subsequently, the state"of"the"art orthopedic applications are summarized, covering interweaved frontiers of therapy and repair/regeneration. The convergence of AM and BTE as well as clinical translation are also discussed. Finally, current challenges and foreseeable opportunities are outlined to foster future growth. This panoramic review could provide helpful guidance for the design, development, and adoption of AM-based biomaterials for next-generation bone healthcare.