Hierarchical evolution of bone biomimicry and osteo-coagulo-immunomodulation induced by the size of biological hydroxyapatite.

Biological hydroxyapatite (BHA) is widely used in the treatment of clinical bone defects due to its good biocompatibility and osteoconductivity. The clinical application of mateiral size is based on the principle of bone defect area adaptation, which contributes to diversity of BHA sizes. However, different sizes correspond to different hierarchical levels of bone biomimicry. As the size changes, the bone biomimicry hierarchy evolves accordingly and influences the process of bone repair and regeneration through osteo-coagulo-immunomodulation, leading to unstable bone graft outcomes. Therefore, this paper reviews the size effect of clinical BHA, analyzes the multilevel structure of natural bone, proposes the evolution of bone biomimetic hierarchy triggered by the size of BHA, and further analyzes the size-media-ted osteo-coagulo-immunomodulation. Based on the hierarchical levels of bone and its osteo-coagulo-immunomodulation effect, we provide a new understanding of the biological principle of the size effect of biomaterials and a theoretical basis for the basic research and clinical application of different size BHA materials.