Immunomodulation Pathogenesis and Treatment of Bone Nonunion

Fractures and bone nonunion commonly require surgical intervention. Serious outcomes of non-healing in the late stages of fracture place a significant financial burden on society and families. Bone nonunion occurs when a fracture stops healing, for many reasons, and leads to a variety of bad outcomes. Numerous factors, including biomechanics and immunology, are involved in the complicated mechanisms of bone nonunion. The immune-inflammatory response plays a significant part in the emergence of bone nonunion, and the occurrence, control, and remission of inflammation in the bone healing process have a significant influence on the ultimate success of bone tissue repair. In the bone microenvironment, immune cells and associated cytokines control bone repair, which is significantly influenced by macrophages, T cells, and fibroblast growth factor. To limit acute inflammation and balance osteogenesis and osteoblastogenesis for tissue repair and regeneration, immune cells and various cytokines in the local microenvironment must be precisely regulated. As a bad complication of late-stage fractures, bone nonunion has a significant effect on patients' quality of life and socioeconomic development. Therefore, in-depth research on its pathogenesis and treatment methods has important clinical value. To provide more precise, focused therapeutic options for the treatment of bone nonunion, we discuss the regulatory roles of the key immune cells engaged in bone healing within the microenvironment during bone healing and their effect on osteogenesis. General stages of fracture healing: healing after fracture is broadly divided into three stages. In the inflammatory phase, platelets release vasoactive mediators and inflammatory factors after the formation of a local hematoma. Macrophages phagocytose necrotic tissues and release signaling factors to promote the recruitment, migration, and proliferation of mesenchymal stem cells. In the proliferation stage, bone scabs are formed, and osteoblasts begin to synthesize woven bone tissue; in the remodeling stage, further bone scabs are formed, and mineralization and structural remodeling occur. image