Osteoimmunology uncovered: How macrophages and biomaterials revolutionize bone healing

With an increasingly aging society, bone defects and fractures have become significant threats to human health and quality of life. Currently, in situ bone repair represents a burgeoning niche within the realm of regenerative materials, achieving notable advancements in bone restoration. Numerous studies have successfully demonstrated the osteogenic potential of various biomaterials. Yet, discrepancies often emerge between in vitro and in vivo outcomes in bone healing, with the intricate in vivo microenvironment frequently failing to replicate the favorable osteogenic effects observed in vitro. The reasons behind these inconsistencies have seldom been explored in previous research. In recent years, advancements in bone microenvironment have revealed that osteoimmunology, of which macrophages are critical components, plays an essential regulatory role in bone regeneration. In this review, the role of macrophages in bone healing is explored and recent developments in biomaterials that promote bone regeneration by modulating osteo-microenvironment from the perspectives of physical and chemical signals are explored. Therefore, this article delves into the impact of macrophages on osteogenesis and provides insights of the mechanism behand it. Understanding how bone immune microenvironment regulate osteogenic outcomes under physical and chemical response can facilitate the design of bone repair materials that better adapt to the complex in vivo bone microenvironment, thereby enhancing their clinical translation.