Local exosomes and Hoxa11 status affect the healing fate during autogenous bone grafting at different sites

The gold standard for the repair of bone defects arising from trauma, infection, resection, or tumors continues to be autogenous bone grafting. The healing of autogenous bone grafts is affected by the following local factors: immunological tolerance, blood supply and biological mechanical stress, which cannot be discussed independently without considering the specific sites of the receptor and donor bones. With respect to bone structure, bone composition, the pattern of osteogenesis or embryonic development origins, the site-related differences in properties between long bone and maxillofacial bone are of great importance among the bones distributed throughout the body. Here, we report that grafting bone blocks from mesoderm-derived femurs has poorer restorative performance than grafting bone blocks from cranial neural crest-derived mandibles. Furthermore, there are disparities in osteogenic repair when the same femur block is transplanted to repair defects in different locations (mandible or femur). Specifically, the femur with mandible as the recipient bed shows advantages in newly formed bone area, bone mineral density, collagen fiber structure and mineralization degree. Mechanistically, exosomes of bone marrow mesenchymal stem cells (BMSCs) from the mandible recipient bed mediate the positive healing influence on femur grafting blocks via the miR-126a-5p/Hoxa11 axis during autogenous transdevelopmental lineage transplantation.