Dental resin for periodontal and tooth root regeneration via metformin to enhance osteogenic and cementogenic differentiation of human periodontal ligament stem cells

Objectives: This study developed a novel dental resin incorporating metformin to repair root caries and periodontitis defects. The objectives were to: (1) Develop a novel dental resin with metformin release to fulfill the clinical requirements for mechanical properties; and (2) investigate the metformin release pattern and the effects on osteogenic and cementogenic differentiation of human periodontal ligament stem cells (hPDLSCs). Methods: Resin specimens with different concentrations of metformin were fabricated. Metformin release was measured using high-performance liquid chromatography. Cellular growth and proliferation on resin were assessed. Alizarin red S staining and an alkaline phosphatase (ALP) activity were determined. Quantitative realtime reverse transcription PCR was employed to determine osteogenic and cementogenic differentiation. Results: The resin with 7.5 % metformin had mechanical properties comparable to those of a commercial control, thus satisfying the clinical requirements (mean +/- SD; n = 10). hPDLSCs showed robust growth and proliferation on resin. At 14 days, the number of hPDLSCs increased by four-fold (p > 0.1). ALP activity in the metformin group was 1.8 times higher than that of control (p < 0.05). At 21 days, the metformin group showed a significant increase in mineral synthesis. Metformin group had cementogenic and osteogenic differentiation values that were 2.5 and 2.3 times higher, respectively, than control without metformin (p < 0.05). Significance: A metformin-resin was formulated that greatly promoted both cementogenic and osteogenic differentiation for the first time. This resin was mechanically strong and supported hPDLSC adhesion, growth and proliferation. This resin substantially enhanced hPDLSC osteogenic and cementogenic differentiation, yielding mineral synthesis of hPDLSCs more than 2-fold that of control without metformin. This new metformin-resin shows promise for the restoration of tooth root caries and the regeneration of periodontal tissues including alveolar bone and cementum.