Advances in 3D-printed and biofabricated scaffolds for bone tissue engineering: materials, fabrication and biological integration.

The worldwide incidence of bone disorders is increasing at an alarming rate, especially among the elderly and those with increased obesity and poor physical activity. Therefore, bone tissue engineering, the process of regenerating diseased or damaged bone, is gaining increasing attention from the scientific community. One of the critical components for tissue engineering is the scaffold, an artificial extracellular matrix that promotes bone formation and regeneration activities. Due to the increasing demands for bone repair, bone tissue scaffolds have been extensively studied in state-of-the-art literature. Nevertheless, many areas related to scaffold manufacturing still offer huge scope for scientific research and development. One such area is the bioprinting of scaffolds, which combines the advantages of three-dimensional printing and biomaterials to create an ideal tissue growth support environment for bone tissue regeneration. This review highlights recent advances in the bioprinting of scaffolds for bone tissue engineering. Taking different biomaterial-based scaffolds as a starting point, the latest research progress and breakthrough points for enhancing the mechanical properties and bioactivities of scaffolds are summarized. Recent scientific breakthroughs related to the tailoring and creative design of scaffolds have been highlighted. New strategies and schemes for subsequent bone scaffold angiogenesis and osteogenesis promotion for new bone tissue regeneration are also discussed. This comprehensive review identifies the shift of research direction, where the biological requirements such as immune response and vascularization is prioritized over fabrication methods. Research gaps on vascularization bottlenecks, methodological and evaluation gaps, fabrication challenges and regulatory hurdles have been identified as well. Future direction of research includes AI assisted design, 4D printing, smart implants, organoid integration and benchmarking standardization of bone tissue implants.