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The Calcium Channel Affect Osteogenic Differentiation of Mesenchymal Stem Cells on Strontium-Substituted Calcium Silicate/Poly-ε-Caprolactone Scaffold

1
Department of Dentistry, Antai Medical Care Cooperation Antai Tian-Sheng Memorial Hospital, Pingtung 928, Taiwan
2
School of Dentistry, Chung Shan Medical University, Taichung City 402, Taiwan
3
Department of Stomatology, Chung Shan Medical University Hospital, Taichung City 402, Taiwan
4
School of Medicine, China Medical University, Taichung City 402, Taiwan
5
Department of Orthopedic Surgery, China Medical University Hospital, Taichung 402, Taiwan
6
3D Printing Medical Research Center, China Medical University Hospital, Taichung City 402, Taiwan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Processes 2020, 8(2), 198; https://doi.org/10.3390/pr8020198
Received: 5 January 2020 / Revised: 30 January 2020 / Accepted: 2 February 2020 / Published: 6 February 2020
(This article belongs to the Special Issue Biofabrication Scaffold in Regenerative Medicine)
There had been a paradigm shift in tissue engineering studies over the past decades. Of which, part of the hype in such studies was based on exploring for novel biomaterials to enhance regeneration. Strontium ions have been reported by others to have a unique effect on osteogenesis. Both in vitro and in vivo studies had demonstrated that strontium ions were able to promote osteoblast growth, and yet at the same time, inhibit the formation of osteoclasts. Strontium is thus considered an important biomaterial in the field of bone tissue engineering. In this study, we developed a Strontium-calcium silicate scaffold using 3D printing technology and evaluated for its cellular proliferation capabilities by assessing for protein quantification and mineralization of Wharton’s Jelly mesenchymal stem cells. In addition, verapamil (an L-type of calcium channel blocker, CCB) was used to determine the mechanism of action of strontium ions. The results found that the relative cell proliferation rate on the scaffold was increased between 20% to 60% within 7 days of culture, while the CCB group only had up to approximately 10% proliferation as compared with the control specimen. Besides, the CCB group had downregulation and down expressions of all downstream cell signaling proteins (ERK and P38) and osteogenic-related protein (Col I, OPN, and OC). Furthermore, CCB was found to have 3–4 times lesser calcium deposition and quantification after 7 and 14 days of culture. These results effectively show that the 3D printed strontium-contained scaffold could effectively stimulate stem cells to undergo bone differentiation via activation of L-type calcium channels. Such results showed that strontium-calcium silicate scaffolds have high development potential for bone tissue engineering. View Full-Text
Keywords: calcium channel blocker; verapamil; strontium; osteogenic; 3D printing calcium channel blocker; verapamil; strontium; osteogenic; 3D printing
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MDPI and ACS Style

Su, T.-R.; Huang, T.-H.; Kao, C.-T.; Ng, H.Y.; Chiu, Y.-C.; Hsu, T.-T. The Calcium Channel Affect Osteogenic Differentiation of Mesenchymal Stem Cells on Strontium-Substituted Calcium Silicate/Poly-ε-Caprolactone Scaffold. Processes 2020, 8, 198.

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