Abstract
Production of a 3D bone construct with high-yield differentiated cells using an appropriate cell source provides a reliable strategy for different purposes such as therapeutic screening of the drugs. Although adult stem cells can be a good source, their application is limited due to invasive procedure of their isolation and low yield of differentiation. Patient-specific human-induced pluripotent stem cells (hiPSCs) can be an alternative due to their long-term self-renewal capacity and pluripotency after several passages, resolving the requirement of a large number of progenitor cells. In this study, a new biphasic 3D-printed collagen-coated HA/β-TCP scaffold was fabricated to provide a 3D environment for the cells. The fabricated scaffolds were characterized by the 3D laser scanning digital microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and mechanical test. Then, the osteogenesis potential of the hiPSC-seeded scaffolds was investigated compared to the buccal fat pad stem cell (BFPSC)-seeded scaffolds through in vitro and in vivo studies. In vitro results demonstrated up-regulated expressions of osteogenesis-related genes of RUNX2, ALP, BMP2, and COL1 compared to the BFPSC-seeded scaffolds. In vivo results on calvarial defects in the rats confirmed a higher bone formation in the hiPSC-seeded scaffolds compared to the BFPSC-seeded groups. The immunofluorescence assay also showed higher expression levels of collagen I and osteocalcin proteins in the hiPSC-seeded scaffolds. It can be concluded that using the hiPSC-seeded scaffolds can lead to a high yield of osteogenesis, and the hiPSCs can be used as a superior stem cell source compared to BFPSCs for bone-like construct bioengineering.
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The authors would like to thank the staff and officials in the Research Institute for Dental Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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This study was financially supported by the School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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All the procedures performed in the studies involving the animals and human were in accordance with the ethical standards of the Iran’s National Committee for Ethics in Biomedical Research. The animal experiments conducted in this study were approved by the Animal Research and Care Committee, the Faculty of Veterinary Medicine, University of Tehran (IBR-UT139615). Ethical approval for obtaining the samples from the humans was given by the Ethics Committee of the Shahid Beheshti University of Medical Sciences (IR.SBMU.RETECH.REC.1396.1301).
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In this study, the BFPSCs were harvested from the healthy donors presenting to the Clinic of Oral and Maxillofacial Surgery, Dental School of Shahid Beheshti University of Medical Sciences in Tehran, Iran. An informed written consent was obtained from all the donors.
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Hashemi, S., Mohammadi Amirabad, L., Farzad-Mohajeri, S. et al. Comparison of osteogenic differentiation potential of induced pluripotent stem cells and buccal fat pad stem cells on 3D-printed HA/β-TCP collagen-coated scaffolds. Cell Tissue Res 384, 403–421 (2021). https://doi.org/10.1007/s00441-020-03374-8
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DOI: https://doi.org/10.1007/s00441-020-03374-8