The calcium channel affect osteogenic differentiation of mesenchymal stem cells on strontium-substituted calcium silicate/poly-ε-caprolactone scaffold

Abstract

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.