Bone microenvironments-regulated biomaterials boost osteonecrosis therapy.

Abstract

Several pathological mechanisms, including vascular endothelial cell injury, osteocyte apoptosis, and excessive osteoclast activation, drive osteonecrosis. The disease progression is further exacerbated by disrupted bone remodeling, immune system dysregulation, and impaired regeneration capacity of blood vessel and bone. In weight-bearing joints, progressive subchondral bone deterioration often leads to joint collapse, resulting in chronic pain, stiffness, and disability. Early intervention, typically involving core decompression combined with bone grafting, is essential to prevent irreversible joint damage. Due to the limited availability of autologous bone, research has increasingly focused on developing advanced artificial bone substitutes. This review systematically summarizes current biomaterial-based strategies for treating osteonecrosis, emphasizing innovative approaches that enhance vascular regeneration and osteogenesis while simultaneously suppressing osteoclast activity and modulating immune responses. It also provides an overview of osteogenic biomaterial fabrication and the mechanisms by which biomaterials mediate tissue regeneration, emerging trends in bioactive material development, and potential strategies for advancing next-generation biomaterials.