Macrophage-mediated immunomodulation in biomaterial-assisted bone repair: Molecular insights and therapeutic prospects

The skeletal system is essential for preserving body structure and facilitating mobility; however, bone diseases frequently result in significant disabilities, necessitating the investigation into biomaterials for bone restoration. Nevertheless, these biomaterials may elicit immune reactions that obstruct the healing process. Macrophages assume a pivotal role in modulating inflammation and sustaining immune homeostasis essential for bone regeneration. A comprehensive understanding of the molecular interactions between biomaterials and macrophages is imperative for the development of sophisticated biomaterials designed to regulate the bone immune environment and promote bone remodeling. This review delves into the generation, polarization, and interaction of macrophages with principal cell types implicated in osteogenesis, detailing the molecular mechanisms by which macrophages influence bone repair and their response to biomaterials. Additionally, it discusses strategies for the precise modulation of macrophage functionality via intelligent mechanisms, and outlines the challenges and constraints in designing biomaterials that integrate bone immune functions. By elucidating these mechanisms and challenges, the review lays the groundwork for the creation of advanced biomaterials endowed with smart bone immunomodulatory capabilities, heralding novel approaches for the treatment of bone defects and the advancement of bone regeneration therapies.