Abstract
Metformin is an old and widely accepted first-line drug for treating type 2 diabetes. Our previous studies demonstrate that metformin can stimulate the osteo/odontogenic differentiation of human-induced pluripotent stem cell-derived mesenchymal stem cells and human dental pulp cells (DPCs). Due to the rapid dilution of metformin from the defect area, the aim of this study was to develop a drug delivery system with controlled release of metformin to promote cell viability and odontogenic differentiation of DPCs favoring dentin regeneration. Calcium phosphate cement (CPC) containing chitosan and metformin as a scaffold was synthesized. DPCs were seeded onto the scaffold, and the viability and proliferation were evaluated at several time points. For osteogenic differentiation analysis, alkaline phosphatase (ALP) activity was tested, cells were stained with Alizarin Red, and the expression of odontogenic markers was evaluated by real-time polymerase chain reaction. DPCs remained viable and attached well to the CPC-chitosan composite scaffold. Moreover, the addition of metformin to the CPC-chitosan composite did not adversely affect cell proliferation, compared to that of CPC control. Our data further revealed that the novel CPC-chitosan-metformin composite enhanced the odontogenic differentiation of DPCs, as evidenced by higher ALP activity, elevated expression of odontoblastic markers, and strong mineral deposition. These results suggest that the new CPC-chitosan-metformin composite is a highly promising scaffold with the potential for tissue engineering applications including dentin regeneration.
Highlights
Dental pulp is often damaged by cariogenic infection, mechanical trauma, and clinical operative procedures
Metformin is important for the differentiation of dental pulp cells (DPCs) with its ability to enhance odontogenic differentiation, the application of metformin was limited in dentin regeneration because of its rapid dilution from the defect area leading to inefficient tissue formation [11]
Based on the initial burst release of metformin and followed by continuous release, the 50 μg metformin was selected in all further experiments. These results showed that metformin release from Calcium phosphate cement (CPC)-chitosan scaffold was sustained and relatively long lasting, to meet the requirement of a drug carrier to last for 2–3 weeks in order to stimulate the odontogenic differentiation of DPCs
Summary
Dental pulp is often damaged by cariogenic infection, mechanical trauma, and clinical operative procedures. Dental pulp regeneration is one of the most promising therapeutic strategies, which would promote the repair of the pulp-dentin complex and improve the patient’s life quality [2]. Stem Cells International endodontic treatment procedures using tissue engineering strategies [3]. Human dental pulp cells (DPCs) as progenitor cells are an excellent cell source for dentin regeneration. DPCs are capable of odontogenic differentiation to form the dentin-pulp complex in dental pulp tissues [7, 8]. Biochemical factors are critical signalling molecules that instruct the DPCs to achieve pulp regeneration. Our previous studies demonstrated that the small molecule compound metformin has osteo/odontogenic effects by promoting the differentiation of human-induced pluripotent stem cell- (hiPSC-) derived mesenchymal stem cells (MSCs) and DPCs [9, 10]. It is important to achieve sustained local release of metformin to the dental pulp exposure site
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
