Strategies for fabricating multi-material bone tissue constructs

Bone is a complex hierarchical tissue with diverse functions that presents numerous challenges for engineering replacements due to its need for structural support and interaction with surrounding tissue for healing. The complexity of its architecture, composition, and biological signaling presents formidable challenges in engineering functional replacements. Traditional bone grafts often suffer from limitations such as donor site morbidity and limited availability, driving the pursuit of advanced biomaterials for bone tissue engineering (BTE). This review highlights the potential of multi-material design as a strategic approach to overcome these limitations by recapitulating the native bone microenvironment. It begins by establishing a foundational understanding of bone's complex structure, current clinical treatment modalities, and the fundamental principles of multi-material design within the context of BTE. Specifically, it delves into the diverse landscape of biomaterials employed, including ceramics for osteoconductivity, polymers for tunable mechanical properties, and metals for load-bearing applications. It then comprehensively explores recent advancements in multi-material scaffolds, highlighting innovative fabrication techniques like 3D printing, electrospinning, and bioprinting, as well as the synergistic combinations of materials that enhance osteogenesis and vascularization. Finally, it addresses this promising approach's current limitations and future perspectives, emphasizing the need for improved in vivo performance and translation to clinical applications.