The effects of local BMP-2 delivery dose on the systemic immune response following traumatic bone injury 4049

Abstract Description As 5-15% of bone fractures fail to heal, trauma immunology has gained recent interest to better understand local and systemic immune responses following musculoskeletal injury. Notably, dysregulated immune responses early in the healing process strongly correlate with poor outcomes, yet effective immunomodulatory interventions remain underdeveloped. Bone Morphogenetic Protein-2 (BMP-2), a potent osteoinductive agent, has shown promise for treating bone injuries but carries significant risk due to inflammation-associated complications. In this study, we assessed how BMP-2 dose modulates systemic immune responses in a rat femoral defect model, hypothesizing that BMP-2 induces a dose-dependent immune response. Defects were stabilized and treated with 0 µg, 3 µg, or 30 µg BMP-2 (n = 7-8/group), and bone formation was analyzed using x-ray and micro-CT. Longitudinal blood samples were collected to evaluate immune cell populations and cytokines. We found that while both 3 µg and 30 µg doses promoted significant bone healing, the 30 µg dose induced a marked, sustained immunosuppression, evidenced by increased circulating T regulatory and myeloid-derived suppressor cells, alongside upregulated pro-inflammatory cytokines. In contrast, the 3 µg dose enhanced bone formation without significant immune modulation. These results highlight a potential pathway to improve BMP-2 safety by optimizing dosage to balance bone repair and immune effects, advancing therapies for traumatic bone injuries. Funding Sources NIH AR069297 Topic Categories Translational and Interventional Immunology (TI)