Immunomodulation Using BMP‐7 and IL‐10 to Enhance the Mineralization Capacity of Bone Progenitor Cells in a Fracture Hematoma‐Like Environment

Abstract Following biomaterial implantation, a failure to resolve inflammation during the formation of a fracture hematoma can significantly limit the biomaterial's ability to facilitate bone regeneration. This study aims to combine the immunomodulatory and osteogenic effects of BMP‐7 and IL‐10 with the regenerative capacity of collagen‐hydroxyapatite (CHA) scaffolds to enhance in vitro mineralization in a hematoma‐like environment. Incubation of CHA scaffolds with human whole blood leads to rapid adsorption of fibrinogen, significant stiffening of the scaffold, and the formation of a hematoma‐like environment characterized by a limited capacity to support the infiltration of human bone progenitor cells, a significant upregulation of inflammatory cytokines and acute phase proteins, and significantly reduced osteoconductivity. CHA scaffolds functionalized with BMP‐7 and IL‐10 significantly downregulate the production of key inflammatory cytokines, including IL‐6, IL‐8, and leptin, creating a more permissive environment for mineralization, ultimately enhancing the biomaterial's osteoconductivity. In conclusion, targeting the onset of inflammation in the early phase of bone healing using BMP‐7 and IL‐10 functionalized CHA scaffolds is a promising approach to effectively downregulate inflammatory processes, while fostering a more permissive environment for bone regeneration.