Controlled Release of BMP-2 from a Heparin-Conjugated Strontium-Substituted Nanohydroxyapatite/Silk Fibroin Scaffold for Bone Regeneration

The objective of this study was to develop heparin-conjugated strontium-substituted hydroxyapatite/silk fibroin (Sr-nHAp/SF-Hep) scaffold loaded bone morphogenetic proteins-2 (BMP-2) with sustained release to improve bone regeneration. The average pore diameters and porosity of Sr-nHAp/SF scaffolds were respectively approximately 150 urn and 90%. The mechanical properties and thermostability of the Sr-nHAp/SF scaffolds were significantly stronger than those of the SF scaffold. The weight of composite scaffolds is higher than that of the SF scaffold in simulated body fluids. The Sr-nHAp/SF scaffold exhibited excellent biological function of bone marrow mesenchymal stem cell (BMSC) proliferation and adhesion. The expression of related osteogenic genes, including osteocalcin, osteopontion, and alkaline phosphatase activity was elevated by Sr-nHAp/SF-Hep-BMP-2 scaffold, which promoted the differentiation of BMSCs into osteoblasts. In vivo results showed that Sr-nHAp/SF-Hep-BMP-2 scaffolds enhanced bone mineral density and improved new bone regeneration, which was accomplished through microcomputed tomography (micro-CT) and histological and histochemical staining analysis. These results demonstrated SrnHAp/SF-Hep-BMP-2 scaffolds with favorable biocompatibility and good mechanical properties have great potential to repair bone defects.