Interaction of Macrophages with Bone Healing Microenvironment: Mechanism and Biomaterials

Extensive bone fractures, which can seriously impact both health and quality of life, cannot easily heal naturally, especially if the patient has an underlying medical condition or is aging. The most promising approach to addressing such fractures is bone regeneration through bone tissue engineering. Bone regeneration is a complex process that consists of three distinct phases: inflammation, repair, and remodeling. Macrophages play a bridging role between the various cells involved in each stage of bone regeneration, interacting with different microenvironments and advancing the bone healing process. Although the origin and function of macrophages have been extensively studied, the mechanisms underlying their interaction with the bone healing microenvironment remain unexplored, including the association of microenvironmental changes with macrophage reprogramming and the role of macrophages in cells in the microenvironment. This review summarizes the bone regeneration process and recent advances in research on interactions between macrophages and the bone healing microenvironment and discusses novel biological strategies to promote bone regeneration by modulating macrophages for the treatment of bone injury and loss. In this review, we focus on the relationship between the bone healing microenvironment and cells during the three stages of bone healing. We focused on the metabolic reprogramming of macrophages by the microenvironment, which in turn leads to alterations in their phenotype, as well as macrophages influencing components of the microenvironment through paracrine secretion. In addition, we present recent advances in the improvement of bone regeneration materials through macrophage modulation, which will be useful for subsequent research and clinical translation.