Fabrication and Characterization of a PDLSCs/BMP-2-PLGA-NP/RADA Peptide Hydrogel Composite for Bone Repair

It is of great interest to develop implantable biomaterial with controlled BMP-2 release. This study aimed to construct a composite (BMP-2/PLGA-NP/RADA) containing periodontal ligament stem cells (PDLSCs), rhBMP-2-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (BMP-2/PLGANP), and self-assembling RADA-16 peptide hydrogel and characterize its osteogenic capacity. PLGA nanoparticles were produced by double-emulsionmethod, which were then incorporated into RADA16 peptide hydrogel with or without PDLSCs. The time course of rhBMP-2 release was measured by ELISA after incubating BMP-2/PLGA-NP and BMP-2/PLGA-NP/RADA in PBS. The osteoinductivity of BMP-2/PLGA-NP and BMP-2/PLGA-NP/RADA in vitro was analyzed by measuring alkaline phosphotase activity and ossification. The in vivo osteogenesis of BMP-2/PLGA-NP/RADA composite was examined by HE and Alizarin Red staining as well as the expression of ALP and OCN genes. The incorporation of PDLSCs and BMP-2/PLGA-NP did not change the appearance of RADA hydrogel whereas BMP-2/PLGA-NP/RADA improved rhBMP-2 release pattern and enhanced osteoinductive ability compared to BMP-2/PLGA-NP. Implantation of BMP-2/PLGA-NP/RADA composite resulted in significant osteogenesis in 4 weeks. These results indicated that stem cells, rhBMP-2loaded PLGA microparticles, and RADA-16 hydrogel composite would be a promising biomaterial for bone repair and regeneration.