Human periodontal ligament stem cell seeding on calcium phosphate cement scaffold delivering metformin for bone tissue engineering

Zeqing Zhao; Jin Liu; Abraham Schneider; Xianling Gao; Ke Ren; Michael D Weir; Ning Zhang; Ke Zhang; Li Zhang; Yuxing Bai; Hockin H K Xu

doi:10.1016/j.jdent.2019.103220

Human periodontal ligament stem cell seeding on calcium phosphate cement scaffold delivering metformin for bone tissue engineering

J Dent. 2019 Dec:91:103220. doi: 10.1016/j.jdent.2019.103220. Epub 2019 Oct 31.

Authors

Zeqing Zhao¹, Jin Liu², Abraham Schneider³, Xianling Gao⁴, Ke Ren⁵, Michael D Weir⁶, Ning Zhang⁷, Ke Zhang⁷, Li Zhang⁷, Yuxing Bai⁸, Hockin H K Xu⁹

Affiliations

¹ Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China; Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA.
² Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA; Key Laboratory of Shanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, China.
³ Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD 21201, USA.
⁴ Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA; Department of Endodontics, Guanghua School and Hospital of Stomatology & Institute of Stomatological Research, Sun Yat-sen University, Guangzhou, China.
⁵ Department of Neural and Pain Sciences, School of Dentistry, & Program in Neuroscience, University of Maryland, Baltimore, MD 21201, USA.
⁶ Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA.
⁷ Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China.
⁸ Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China. Electronic address: [email protected].
⁹ Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA; Member, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: [email protected].

PMID: 31678476
DOI: 10.1016/j.jdent.2019.103220

Abstract

Objectives: (1) develop a CPC-metformin scaffold with hPDLSC seeding for bone tissue engineering; and (2) investigate the effects of CPC-metformin scaffold on hPDLSC proliferation, osteogenic differentiation and bone matrix mineralization for the first time.

Methods: hPDLSCs were harvested from extracted teeth. CPC scaffolds (with or without metformin) were prepared. Three groups were tested: (1) control group (growth medium); (2) osteogenic group (osteogenic medium); (3) metformin + osteogenic group (CPC-metformin scaffold, cultured in osteogenic medium). hPDLSC viability, osteogenic differentiation and mineralization were measured. SEM was used to examine cell morphology.

Results: After culturing for 14 days, all three groups demonstrated excellent hPDLSC attachment and viability, as shown in live-dead staining, CCK-8 assay, and SEM examinations. The osteogenic group had 3-8 folds, 5 folds and 6 folds of increases in osteogenic gene expressions, ALP activity and mineral synthesis, compared to control group. Furthermore, the metformin + osteogenic group had 3-fold to 4-fold increases over those of the osteogenic group in osteogenic gene expressions, ALP activity and mineral synthesis.

Conclusions: hPDLSCs were demonstrated to be a potent cell source for bone engineering. The novel CPC-metformin-hPDLSC construct is highly promising to enhance bone repair and regeneration efficacy in dental, craniofacial and orthopedic applications.

Keywords: Bone tissue engineering; Calcium phosphate cement; Human teeth; Metformin; Osteogenic differentiation; Periodontal ligament stem cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Calcium Phosphates / chemistry*
Cell Differentiation
Cells, Cultured
Humans
Metformin*
Osteogenesis*
Periodontal Ligament*
Stem Cells
Tissue Engineering*
Tissue Scaffolds / chemistry*

Substances

Calcium Phosphates
Metformin