Unraveling the mechanisms behind porous calcium phosphate ceramics-instructed osteoinduction: a systematic review.

Calcium phosphate (CaP) ceramics are widely used in bone defect repair due to their osteoconductivity. However, conventional CaP ceramics lack intrinsic osteoinductivity. In contrast, some newly developed osteoinductive CaP ceramics with specific physicochemical properties have shown great potential as a synthetic alternative to autologous bone grafting. However, the limited understanding of the mechanisms of osteoinductive CaP ceramics has hindered the rational design and clinical translation. In this review, we systematically summarized the importance of pore architecture, grain size, surface features, and chemical composition of osteoinductive CaP ceramics, and emphasized the series of cellular and physiological events triggered by this special material. In particular, we highlighted macrophage-osteoclast coupling as a potential central regulatory axis that integrates immune responses with bone remodeling. The polarized macrophages not only orchestrate stem cell recruitment and osteogenic differentiation, but also directly modulate osteoclastogenesis, which in turn shapes the osteoinductive microenvironment. Overall, this review synthesizes recent advances, challenges, and hypotheses in the mechanisms of osteoinductive CaP ceramics, while the in-depth discussion on immune-bone crosstalk provides a conceptual framework for predicting osteoinductive outcomes and offers new inspiration for optimizing advanced CaP ceramics with superior osteoinductive potential.