Injectable calcium phosphate scaffold with iron oxide nanoparticles to enhance osteogenesis via dental pulp stem cells

Abstract

Literature search revealed no systematic report on iron oxide nanoparticle-incorporating calcium phosphate cement scaffolds (IONP-CPC). The objectives of this study were to: (1) use γFe₂O₃ nanoparticles (γIONPs) and αFe₂O₃ nanoparticles (αIONPs) to develop novel IONP-CPC scaffolds, and (2) investigate human dental pulp stem cells (hDPSCs) seeding on IONP-CPC for bone tissue engineering for the first time. IONP-CPC scaffolds were fabricated. Physiochemical properties of IONP-CPC scaffolds were characterized. hDPSC seeding on scaffolds, cell proliferation, osteogenic differentiation and bone matrix mineral synthesis by cells were measured. Our data demonstrated that the osteogenic differentiation of hDPSCs was markedly enhanced via IONP incorporation into CPC. Substantial increases (about three folds) in ALP activity and osteogenic gene expressions were achieved over those without IONPs. Bone matrix mineral synthesis by the cells was increased by two- to three folds over that without IONPs. The enhanced cellular osteogenesis was attributed to: (1) the surface nanotopography of IONP-CPC scaffold, and (2) the cell internalization of IONPs released from IONP-CPC scaffold. Our results demonstrate that the novel CPC functionalized with IONPs is promising to promote osteoinduction and bone regeneration. In conclusion, it is highly promising to incorporate γIONPs and αIONPs into CPC scaffold for bone tissue engineering, yielding substantially better stem cell attachment, spreading and osteogenic differentiation, and much greater bone mineral synthesis by the seeded cells. Therefore, novel CPC scaffolds containing γIONPs and αIONPs are promising for dental, craniofacial and orthopaedic applications to substantially enhance bone regeneration.

Keywords:

• Iron oxide nanoparticles
• nanotopography
• cell internalization
• calcium phosphate cement
• human dental pulp stem cells
• osteogenesis

Acknowledgements

We thank Dr Ashraf F. Fouad for providing the hDPSCs, Peng Wang for discussions, and Zhichao Lou for AFM experiment.

Disclosure statement

The authors declare no conflict of interests.

Additional information

Funding

This study was supported by National Institutes of Health [R01 DE14190] and [R21 DE22625] (HX), National Natural Science Foundation of China [81771044] (YX), Jiangsu Medical Youth Talent [QNRC2016853] (YX), China Postdoctoral Science Foundation [2015M571647] (YX), Postdoctoral Foundation of Jiangsu [1402044B] (YX), National Key Research Project [2016YFA0201704/2016YFA0201700] (FZ), Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions [2014–37] (FZ), and University of Maryland School of Dentistry bridge fund (HX).