Bioactive Materials-Mediated Regulation of Bone Marrow Microenvironment: Mechanistic Insights and Therapeutic Potentials.

The bone marrow microenvironment(BME) maintains bone homeostasis through multi-cellular cooperation and signal crosstalk, its dysregulation drives pathological bone loss. In recent years, Materiobiology, a scientific discipline studying how biomaterial properties affect biological functions, has opened new avenues for the precise regulation of this complex microenvironment. Biomaterials enable sophisticated regulation of the BME through biomimetic design and functionalization strategies. They not only activate osteoblast signaling pathways to promote bone formation but also inhibit osteoclast differentiation and bone resorption functions. Additionally, they integrate nerve and vascular regeneration processes with immunomodulatory mechanisms to optimize stem cell behavior and improve the tissue repair microenvironment. This review comprehensively summarizes advances in biomaterial-mediated BME regulation, emphasizing interdisciplinary integration and intelligent material development to overcome the limitations of conventional therapies. The innovation of intelligent materials lies in their ability to mimic biological systems. Recent research has leveraged generative design models to engineer new thiol-containing antimicrobial peptides. These approaches achieve spatiotemporal coordination of cellular interactions and functional reconstruction during bone regeneration. Future efforts need to address challenges in material stability, personalized adaptation, and clinical translation, promoting cross-scale therapeutic innovation from molecular intervention to tissue regeneration, providing revolutionary solutions for bone metabolic diseases and complex defect repair.