Scaffolds of bioactive glass (Bioglass®) combined with recombinant human bone morphogenetic protein -9 (rhBMP-9) for tooth extraction site preservation

Objective: The study aimed to investigate the osteogenic ability of bioactive glass (bioglass) combined with recombinant human bone morphogenetic protein-9 (rhBMP-9) on rat bone marrow mesenchymal stem cells (BMSCs) in vitro. The study also compares bone regeneration using rhBMP9 soaked with different carrier systems, including bioglass or collagen membranes (BioGide, BG) in a rat alveolar bone site preservation model in vivo.

Methods: Scanning electron microscopy was employed to analyze bioglass surface. The absorption and release potential of rhBMP9 from bioglass were researched by ELISA.The cell viability, adhesion, proliferation, and differentiation were assessed for rhBMP9 soaked on bioglass by cck-8 kit, alkaline phosphatase (ALP) activity assay, alizarin red staining, and real-time PCR. Furthermore, prepared grafts (bioglass + BG, bioglass/rhBMP9+BG, and bioglass + BG/rhBMP9) were implanted into the maxillary right first incisor sockets of Sprague Dawley rats for 8 weeks, and new bone formation was quantified by micro-CT and histological analysis.

Results: Bioglass absorbed rhBMP9 dramatically and released it with a slow and stable speed within ten days by ELISA. When used with cck-8 kit detection, cell viability at 24 h, cell adhesion rate at 8 h, and cell proliferation at 1, 3, and 5 days were decreased in the bioglass alone group versus the control group but slightly increased with the addition of rhBMP9. Similarly, the effect of osteogenic differentiation on bioglass increased significantly when combined with rhBMP9 by upregulating the expression of ALP, mineralized matrix, and osteogenic related genes. Furthermore, both bioglass/rhBMP9+BG samples and bioglass + BG/rhBMP9 samples significantly improved several bone formation parameters compared with bioglass + BG samples. Interestingly, bioglass + BG/rhBMP9 samples demonstrated more bone regeneration in rat site preservation models.

Conclusions: Both bioglass and BG can be applied in GBR surgery as effective carriers of rhBMP9. However, BG may be more suitable than bioglass for investigating site preservation effect after tooth extraction when associated with rhBMP9 and provides a practical clinical solution to the problem of bone deficiency caused by alveolar bone atrophy.