Abstract
In this study, we fabricated gelatin/nano-hydroxyapatite/metformin scaffold (GHMS) and compared its effectiveness in bone regeneration with extraction-only, Sinbone, and Bio-Oss Collagen® groups in a critical size rat alveolar bone defect model. GHMS was synthesized by co-precipitating calcium hydroxide and orthophosphoric acid within gelatin solution, incorporating metformin, and cross-linked by microbial transglutaminase. The morphology, characterization, and biocompatibility of scaffold were examined. The in vitro effects of GHMS on osteogenic gene and protein expressions were evaluated. In vivo bone formation was assessed in a critical size rat alveolar bone defect model with micro-computed tomography and histological examination by comparing GHMS with extraction-only, Sinbone, and Bio-Oss Collagen®. The synthesized GHMS had a highly interconnected porous structure with a mean pore size of 81.85 ± 13.8 µm. GHMS exhibited good biocompatibility; promoted ALPL, RUNX2, SP7, BGLAP, SPARC and Col1a1 gene expressions; and upregulated the synthesis of osteogenic proteins, including osteonectin, osteocalcin, and collagen type I. In critical size rat alveolar bone defects, GHMS showed superior bone regeneration compared to extraction-only, Sinbone, and Bio-Oss Collagen® groups as manifested by greater alveolar ridge preservation, while more bone formation with a lower percentage of connective tissue and residual scaffold at the defect sites grafted with GHMS in histological staining. The GHMS presented in this study may be used as a potential bone substitute to regenerate alveolar bone. The good biocompatibility, relatively fast degradation, interconnected pores allowing vascularization, and higher bioactivity properties of the components of the GHMS (gelatin, nHA, and metformin) may contribute to direct osteogenesis.
Highlights
After loss of a natural tooth, the alveolar ridge undergoes resorption as a normal physiological process
Results of the WST-1 assays showed no significant differences in the L929 fibroblast viability when cultured with negative control, 50 μM metformin, gelatin/nano-hydroxyapatite nanocomposite scaffold (GHS), and Gelatin/Nano-Hydroxyapatite/Metformin Scaffold (GHMS) compared with blank control (Figure 2A), indicating the cells were able to grow and proliferate well in the presence of GHMS
In a critical size rat alveolar bone defect, we have demonstrated the superior performance of metformin-loaded gelatin/nHA sponge (GHMS) in bone regeneration compared with extraction-only, calcium phosphate–only (Sinbone), and calcium phosphate plus collagen (Bio-Oss Collagen® ) control groups
Summary
After loss of a natural tooth, the alveolar ridge undergoes resorption as a normal physiological process. To overcome the issue of bone loss, different materials, used in various combinations, have been grafted into the extraction socket to achieve alveolar ridge preservation (ARP). These include autogenous bone grafts, allografts, xenografts, and alloplasts that come in various forms, including particulate granules and sponges [1]. The performance of gelatin/nHA/metformin scaffold (GHMS) in the form of sponge to promote alveolar bone regeneration in a critical size rat alveolar bone defect model was evaluated in comparison with commercially available xenograft (Bio-Oss. Collagen® ) and alloplast (Sinbone granules)
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