Immunomodulation in Bone Tissue Engineering: Recent Advancements in Scaffold Design and Biological Modifications for Enhanced Regeneration

Bone defects, whether caused by trauma, cancer, infectious diseases, or surgery, can significantly impair people's quality of life. Although autografts are the gold standard for treating bone defects, they often fall short in adequately forming bone tissue. The field of bone tissue engineering has made strides in using scaffolds with various biomaterials, stem cells, and growth factors to enhance bone healing. However, some biological structures do not yield satisfactory therapeutic outcomes for new bone formation. Recent studies have shed light on the crucial role of immunomodulation, specifically the interaction between the implanted scaffold and host immune systems, in bone regeneration. Immune cells, particularly macrophages, are pivotal in the inflammatory response, angiogenesis, and osteogenesis. This review delves into the immune system's mechanism toward foreign bodies and the recent advancements in scaffolds' physical and biological properties that foster bone regeneration by modulating macrophage polarization to an anti-inflammatory phenotype and enhancing the osteoimmune microenvironment.