Recombinant human bone morphogenetic protein-2 (rhBMP-2) induced macrophage biphasic polarization regulated by dexamethasone in vivo.

Objectives: To evaluate macrophage polarization dynamics in vivo after implantation of recombinant human bone morphogenetic protein-2 (rhBMP-2) incorporated biomaterials, with a focus on dose-dependent effects and polarization modulation strategies.

Methods: A murine dorsal subcutaneous implantation model was utilized to analyze macrophage responses to varying concentrations of rhBMP-2-loaded biomaterials with or without dexamethasone (Dex). Polarization patterns were assessed through phenotypic characterization and cytokine expression profiling.

Results: Elevated rhBMP-2 concentrations amplified macrophage polarization activities, and concurrent activation of M1 and M2 polarization was observed accompanied by enhanced expression of both pro-inflammatory (M1-associated) and anti-inflammatory (M2-associated) cytokines. Dexamethasone co-administration effectively attenuated pro-inflammatory polarization patterns induced by high-dose rhBMP-2 implants while preserving regenerative cytokine expression.

Conclusions: Optimized rhBMP-2 dosage facilitates a balanced macrophage polarization state, creating a pro-regenerative microenvironment through coordinated inflammatory resolution and tissue remodeling signals. For clinical applications requiring high rhBMP-2 doses, concurrent short-term anti-inflammatory therapy (e.g., dexamethasone) is recommended to mitigate excessive M1 polarization without compromising osteoinductive capacity.