Injectable, regenerative and anti-infective PEGylated polyglycerol sebacate-modified calcium phosphate cements triggered by berberine and rhBMP-2 for oral bone defect repair.

Adequate bone healing around the implant is critical to its clinical success. For decades, biomimetic composites with integrated osteogenic and anti-infective capacities have been a cornerstone of translational research targeting oral bone defect repair. Herein, we report the engineering of a novel composite: functional molecule-loaded, PEGylated polyglycerol sebacate (PEGS)-modified calcium phosphate cement (PCPC) composite. Specifically, calcium phosphate cement (CPC) was functionalized with PEGS, a hydrophilic elastomer, followed by the co-immobilization of berberine (BBR), a clinically approved anti-inflammatory agent, and recombinant human bone morphogenetic protein-2 (rhBMP-2), a potent osteogenic cytokine, to fabricate the PCPC composite.The optimized PCPC formulation-incorporating 250 μg of BBR and 2 μg of rhBMP-2 per gram of composite-exhibited superior cytocompatibility, robust mechanical performance, and desirable biodegradability. Notably, in vitro assays demonstrated that BBR incorporation exerted a synergistic effect with rhBMP-2, enhancing the osteogenic differentiation of MC3T3-E1 and inducing the polarization of anti-inflammatory M2 macrophages. In vivo evaluations further verified that BBR/rhBMP-2-loaded PCPC composites significantly accelerated mandibular bone regeneration and mitigated local inflammatory responses relative to unloaded PCPC controls. Collectively, this injectable, immunomodulatory, and osteoinductive PCPC composite emerges as a promising therapeutic platform for oral bone defect repair, providing novel insights into the rational design of next-generation dual-functional biomaterials.