Recent advances in immunomodulatory hydrogels biomaterials for bone tissue regeneration

There is a high incidence of fractures in clinical practice and therapy. The repairment of critical size defects in the skeletal system remains a huge challenge for surgeons and researchers, which can be overcame by the application of bone tissue-engineered biomaterials. An increasing number of investigations have revealed that the immune system plays a vital role in the repair of bone defects, especially macrophages, which can modulate the integration of biomaterials and bone regeneration in multiple ways. Therefore, it has become increasingly important in regenerative medicine to regulate macrophage polarization to prevent inflammation caused by biomaterial implantation. Recent studies have stressed the importance of hydrogel-based modifications and the incorporation of various cellular and molecular signals for regulating immune responses to promote bone tissue regeneration and integrate biomaterials. In this review, we first elaborate briefly on the described the general physiological mechanism and process of bone tissue regeneration. Then, we summarized the immunomodulatory role macrophages play in bone repair. In addition, the role of hydrogel-based immune modification targeting macrophage modulation in accelerating and enhancing bone tissue regeneration was also discussed. Finally, we highlighted future directions and research strategies related to hydrogel optimization for the regulation of the immune response during bone regeneration and healing.