Novel metformin-containing resin promotes odontogenic differentiation and mineral synthesis of dental pulp stem cells
This represents the first report on the development of metformin-containing dental resins. The objectives were to use the resin as a carrier to deliver metformin locally to stimulate dental cells for dental tissue regeneration and to investigate the effects on odontogenic differentiation of dental pulp stem cells (DPSCs) and mineral synthesis. Metformin was incorporated into a resin at 20% by mass as a model system. DPSC proliferation attaching on resins was evaluated. Dentin sialophosphoprotein (DSPP), dentin matrix phosphoprotein 1 (DMP-1), alkaline phosphatase (ALP), and runt-related transcription factor 2 (Runx2) genes expressions were measured. ALP activity and alizarin red staining (ARS) of mineral synthesis by the DPSCs on resins were determined. DPSCs on metformin-containing resin proliferated well (mean ± SD; n = 6), and the number of cells increased by 4-fold from 1 to 14 days (p > 0.1). DSPP, ALP, and DMP-1 gene expressions of DPSCs on metformin resin were much higher than DPSCs on control resin without metformin (p < 0.05). ALP activity of metformin group was 70% higher than that without metformin at 14 days (p < 0.05). Mineral synthesis by DPSCs on metformin-containing resin at 21 days was 9-fold that without metformin (p < 0.05). A novel metformin-containing resin was developed, achieving substantial enhancement of odontoblastic differentiation of DPSCs and greater mineral synthesis. The metformin resin is promising for deep cavities and perforated cavities to stimulate DPSCs for tertiary dentin formation, for tooth root coatings with metformin release for periodontal regeneration, and for root canal fillings with apical lesions to stimulate bone regeneration.
KeywordsDental resin Metformin Odontoblastic differentiation Dental pulp stem cells Mineral synthesis Tissue regeneration
We are grateful to Drs. Bing Song, Wei Qin, and Laurence C. Chow for discussions and experimental help.
This work was supported by University of Maryland School of Dentistry Bridging Fund (HX) and University of Maryland Seed Grant (HX), National Institutes of Health/National Institute of Dental and Craniofacial Research Grant R01 DE023578 (AS), National Natural Science Foundation of China (81870759) and International Science and Technology Cooperation Program of Sichuan Province 2017HH0008 (LC).
Compliance with ethical standards
The procedure was approved by the Institutional Review Board of the University of Maryland Baltimore.
Conflict of interest
The authors declare that there is no conflict of interest.
- 16.Murray PE, About I, Lumley PJ, Franquin JC, Remusat M, Smith AJ. Cavity remaining dentin thickness and pulpal activity. Am J Dent. 2002;15(1):41–6.Google Scholar
- 65.Pradeep AR, Patnaik K, Nagpal K, Karvekar S, Ramamurthy BL, Naik SB, et al. Efficacy of locally-delivered 1% metformin gel in the treatment of intrabony defects in patients with chronic periodontitis: a randomized, controlled clinical trial. J Investig Clin Dent. 2016;7(3):239–45.CrossRefGoogle Scholar