Metformin-loaded β-TCP/CTS/SBA-15 composite scaffolds promote alveolar bone regeneration in a rat model of periodontitis

Abstract

Periodontitis is a progressive infectious inflammatory disease, which leads to alveolar bone resorption and loss of periodontal attachment. It is imperative for us to develop a therapeutic scaffold to repair the alveolar bone defect of periodontitis. In this study, we designed a new composite scaffold loading metformin (MET) by using the freeze-drying method, which was composed of β-tricalcium phosphate (β-TCP), chitosan (CTS) and the mesoporous silica (SBA-15). The scaffolds were expected to combine the excellent biocompatibility of CTS, the good bioactivity of β-TCP, and the anti-inflammatory properties of MET. The MET-loaded β-TCP/CTS/SBA-15 scaffolds showed improved cell adhesion, appropriate porosity and good biocompatibility in vitro. This MET composite scaffold was implanted in the alveolar bone defects area of rats with periodontitis. After 12 weeks, Micro-CT and histological analysis were performed to evaluate different degrees of healing and mineralization. Results showed that the MET-loaded β-TCP/CTS/SBA-15 scaffolds promoted alveolar bone regeneration in a rat model of periodontitis. To our knowledge, this is the first report that MET-loaded β-TCP/CTS/SBA-15 scaffolds have a positive effect on alveolar bone regeneration in periodontitis. Our findings might provide a new and promising strategy for repairing alveolar bone defects under the condition of periodontitis.

In Vivo Bone Tissue Engineering Strategies: Advances and Prospects

“…Tricalcium phosphate (TCP) is a tertiary calcium phosphate, and it is widely used in scaffold-based BTE [ 115 , 116 , 117 ]. TCP is a biodegradable material rich with phosphorus and calcium, and it is commonly used in combination with polymers as a composite scaffold [ 118 ], or drug-loaded material [ 119 ]. However, low biodegradability rate is considered as a drawback of TCP scaffolds.…”

The Potential Therapeutic Role of Metformin in Diabetic and Non-Diabetic Bone Impairment

“…In a periodontitis rat model, local administration of chitosan-metformin based intra pocket dental film led to the reduction of alveolar bone destruction and displayed good antibacterial activity [ 78 ]. Additionally, the metformin-loaded b-tricalcium phosphate/Chitosan/mesoporous silica scaffolds implanted in the region of alveolar bone malformations in rats suffering from periodontitis promoted alveolar bone regeneration [ 79 ]. In another bone tissue engineering study, the group with metformin plus osteogenic had three- to four-fold increases over those of the osteogenic alone group in osteogenic gene expressions, ALP activity, and mineral synthesis, which demonstrated that human periodontal ligament stem cell (hPDLSCs) was a potent cell source for bone engineering and the calcium phosphate cement (CPC)-metformin scaffold with hPDLSCs was a highly promising construct to promote bone repair and regeneration effectively in craniofacial, dental, and orthopedic applications [ 80 ].…”

Research Progress of Metformin in Tissue Regeneration

“…Met is a potent drug that promotes the differentiation of bone marrow mesenchymal stem cells towards osteogenesis. Studies have shown that a β-TCP/CTS/SBA-15 scaffold loaded with Met promotes alveolar bone regeneration in a rat model of periodontitis without cytotoxic effects [4]. The chitosan (CTS) in the scaffold acts as a wound healing agent and the β-tricalcium phosphate (β-TCP) has osteoconductive properties.…”