Four-Dimensional Perspective on Biomimetic Design and Fabrication of Bone Scaffolds for Comprehensive Bone Regeneration

Bone tissue engineering considers bone scaffolds as a key method for repairing critical-sized bone defects. Bone's unique combination of organic and inorganic elements, porous structure, and mechanical strength is crucial. However, many artificial scaffolds overlook the potential disruption to the natural bone repair process, hindering clinical translation. We propose a biomimetic perspective to design scaffolds that closely replicate natural bone's composition, structure, strength, and physiological process of bone repair. The biomimetic design of bone scaffolds across four dimensions significantly extends the concept of bone tissue engineering. In this review, the evolution of the bone repair concept is first briefly summarized. Then, we analyze the characteristics of bone composition, structure, mechanics, and bone repair in the physiological state based on the biomimetic concept. Comprehensive strategies for biomimetic scaffold fabrication are discussed, and future development perspectives are offered, advocating the biomimetic concept as a guiding principle for future scaffold design and fabrication.