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

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.