Biomimetic Fabrication and Osteogenic Effects of E7BMP-2 Peptide Coassembly Microspheres Based α-Tricalcium Phosphate with Silk Fibroin.

Abstract

The repair and reconstruction of bone defects remain a challenge in orthopedics. Inadequate mechanical qualities, poor biocompatibility, and insufficient osteoconductivity are some of the issues facing current bone healing materials. Better materials that can replicate the composition and functionality of natural bone, promote quick and full healing, and reduce the likelihood of rejection and infection are desperately needed. Bone tissue engineering, combining biomaterial scaffolds and pro-osteogenic drugs, provides support in the repair and regeneration of bone defects. The development of an effective scaffold for bone defect repair is an urgent clinical need. The present study investigates the feasibility of using microspheres based on α-tricalcium phosphate and fibroin as an osteoconductive matrix and a carrier for controlled local delivery of the E7BMP-2 peptide, in which the E7 domain confers a calcium chelation property, while the BMP-2 mimicking peptide induces bone formation. We prepared α-tricalcium phosphate/silk fibroin (α-TCP/SF) microspheres through a high voltage electric field based on the protocol of α-TCP/SF bone cement slurry. This α-TCP/SF microspheres-based system was designed for delivery vehicles of the modified BMP-2 peptide by the E7 domain to realize sustainable and steady release of the peptide. In vitro cell tests and the experimental model of cranial bone defects in rats were used to investigate the pro-osteogenic benefits. The results demonstrated that the E7BMP-2 peptide-bound microspheres functioned as a sustained release system for the peptide and enhanced osteogenic differentiation of bone marrow mesenchymal stem cells in rat calvarial defects. Additionally, toxicity studies showed that microspheres have good biocompatibility and safety. Thus, these E7BMP-2 peptide-bound α-TCP/SF microspheres provide a promising therapeutic strategy for the treatment of bone defects.