Immunomodulatory Properties: The Accelerant of Hydroxyapatite-Based Materials for Bone Regeneration

The immunoinflammatory response is the prerequisite step for wound healing and tissue regeneration, and the immunomodulatory effects of biomaterials have attracted increasing attention. Hydroxyapatite [Ca₁₀(PO₄)₆(OH)₂] (HAp), a common calcium phosphate ceramic, due to its structural and functional similarity to the inorganic constituent of natural bones, has been developed for different application purposes such as bone substitutes, tissue engineering scaffolds, and implant coatings. Recently, the interaction between HAp-based materials and the immune system (various immune cells), and the immunomodulatory effects of HAp-based materials on bone tissue regeneration have been explored extensively. Macrophages-mediated regenerative effect by HAp stimulation occupies the mainstream status of immunomodulatory strategies. The immunomodulation of HAp can be manipulated by tuning the physical, chemical, and biological cues such as surface functionalization (physical or chemical modifications), structural and textural characteristics (size, shape, and surface topography), and the incorporation of bioactive substances (cytokines, rare-earth elements, and bioactive ions). Therefore, HAp ceramic materials can contribute to bone regeneration by creating a favorable osteoimmune microenvironment, which would provide a more comprehensive theoretical basis for their further clinical applications. Considering the rapidly developed HAp-based materials as well as their excellent biological performances in the field of regenerative medicine, this review discusses the recent advances concerning the immunomodulatory methods for HAp-based biomaterials and their roles in bone tissue regeneration. Impact statement This review summarized the immunomodulatory methods for hydroxyapatite-based biomaterials in bone tissue regeneration, and further discussed the affecting factors of immunomodulation as well as the challenges for the immunomodulatory strategies. The comprehensive understanding of immunomodulatory strategies for tissue regeneration would provide more guidance for the development of novel hydroxyapatite composite biomaterials.