The immune system and biomaterials exhibit a well-documented synergistic interplay, essential for bone defect healing. Calcium phosphate (CaP) biomaterials, notably hydroxyapatite, β-tricalcium phosphate, and biphasic calcium phosphate, are widely employed as bone substitutes due to their inherent osteoconductivity. A key challenge for synthetic CaPs is augmenting their osteoinductive potential. Indeed, the limited translation of biomaterials into clinical practice may largely stem from insufficient immunomodulatory understanding. Current evidence reveals the complex host immune response to CaPs, which is mediated by physical and biochemical properties. Harnessing immunomodulatory strategies could bridge inflammatory modulation and osteogenesis, thereby enhancing bone regeneration. This review systematically analyzes recent advances in the molecular mechanisms of immune cell responses to CaPs during bone defect healing, deepening our understanding of immunomodulatory strategies for bone regeneration. Furthermore, key knowledge gaps are highlighted to inspire the development of spatiotemporally responsive CaPs for bone tissue engineering.
Impact Statement
A deeper insights of CaPs immunomodulation in bone regeneration will guide the fabrication of osteoinductive biomaterials. This review elucidates how CaPs modulate heterogeneous immune responses, particularly macrophage polarization, which is critical for postimplantation inflammation resolution and osteogenesis. These insights will facilitate the development of immunomodulatory CaPs for future clinical practice.
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