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Novel metformin-containing resin promotes odontogenic differentiation and mineral synthesis of dental pulp stem cells

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Abstract

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.

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Acknowledgments

We are grateful to Drs. Bing Song, Wei Qin, and Laurence C. Chow for discussions and experimental help.

Funding

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).

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Authors and Affiliations

  1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral, Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China

    Suping Wang & Lei Cheng

  2. Department of Advanced Oral Sciences and Therapeutics, University of Maryland School of Dentistry, Baltimore, MD, 21201, USA

    Suping Wang, Yang Xia, Michael D. Weir, Mark A. Reynolds, Lei Cheng & Hockin H. K. Xu

  3. Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China

    Yang Xia

  4. Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD, 21201, USA

    Tao Ma & Abraham Schneider

  5. Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD, 21201, USA

    Ke Ren

  6. Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD, 21201, USA

    Yan Shu

  7. Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, 21201, USA

    Yan Shu, Abraham Schneider & Hockin H. K. Xu

  8. Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA

    Hockin H. K. Xu

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  1. Suping Wang
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  2. Yang Xia
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  3. Tao Ma
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  7. Yan Shu
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  9. Abraham Schneider
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  10. Hockin H. K. Xu
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Correspondence to Lei Cheng, Abraham Schneider or Hockin H. K. Xu.

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Wang, S., Xia, Y., Ma, T. et al. Novel metformin-containing resin promotes odontogenic differentiation and mineral synthesis of dental pulp stem cells. Drug Deliv. and Transl. Res. 9, 85–96 (2019). https://doi.org/10.1007/s13346-018-00600-3

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