Localized and sustained release of Puerarin from a calcium phosphate hydrogel enhances immunomodulatory bone repair by modulating pro-healing macrophage phenotype transitions

Manipulating the immune microenvironment is crucial for bone repair, with macrophages serving as key regulators. Their polarization state significantly influences bone healing. In this study, we examined the immunoregulatory effects of Puerarin, particularly its ability to modulate macrophage activity. Our findings reveal that Puerarin promotes macrophage polarization toward the M2 (anti-inflammatory, pro-healing) phenotype, while suppressing the M1 (pro-inflammatory) phenotype. This shift enhanced the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. To harness these effects, we incorporated Puerarin into β-tricalcium phosphate/collagen type I (β-TCP/Col I) scaffolds, creating a sustained-release system. In a rat cranial defect model, Puerarin-loaded scaffolds fostered a pro-healing immune microenvironment and accelerated endogenous osteogenesis at the defect site. In conclusion, Puerarin-loaded scaffolds show significant potential for bone tissue engineering due to their combined osteoinductive and immunomodulatory properties. This herbal-based approach offers promising prospects for developing safer, more effective strategies for bone repair.