Double-edged effects caused by magnesium ions and alkaline environment regulate bioactivities of magnesium-incorporated silicocarnotite in vitro

Abstract

Magnesium (Mg) is an important element for its enhanced osteogenic and angiogenic properties in vitro and in vivo, however, the inherent alkalinity is the adverse factor that needs further attention. In order to study the role of alkalinity in regulating osteogenesis and angiogenesis in vitro, magnesium-silicocarnotite [Mg-Ca5(PO4)2SiO4, Mg-CPS] was designed and fabricated. In this study, Mg-CPS showed better osteogenic and angiogenic properties than CPS within 10 wt.% magnesium oxide (MgO), since the adversity of alkaline condition was covered by the benefits of improved Mg ion concentrations through activating Smad2/3-Runx2 signaling pathway in MC3T3-E1 cells and PI3K-AKT signaling pathway in human umbilical vein endothelial cells in vitro. Besides, provided that MgO was incorporated with 15 wt.% in CPS, the bioactivities had declined due to the environment consisting of higher-concentrated Mg ions, stronger alkalinity and lower Ca/P/Si ions caused. According to the results, it indicated that bioactivities of Mg-CPS in vitro were regulated by the double-edged effects, which were the consequence of Mg ions and alkaline environment combined. Therefore, if MgO is properly incorporated in CPS, the improved bioactivities could cover alkaline adversity, making Mg-CPS bioceramics promising in orthopedic clinical application for its enhancement of osteogenesis and angiogenesis in vitro.

Deciphering the role of faujasite-type zeolites as a cation delivery platform to sustain the functions of MC3T3-E1 pre-osteoblastic cells

“…The slow release kinetics described herein may also avoid a Mg burst release, known to affect the pH value. Indeed, Wu et al 51 showed that progressive exposure to Mg 2+ ions released from bioceramic substrates enhanced osteogenesis of MC3T3-E1 cells without pH-related damage to the cell integrity. After 7 days, the Ca 2+ cation concentrations were fairly proportional to the mass of zeolites i.e.…”

“…4(b)), a range for which the Ca-dependence of the mode and the strength of adhesion is significant. As previously emphasized, it is likely that such a Ca-dependence of cell morphology and proliferation is related either to surface receptors (CaSR) 51 or to G-coupled proteins such as calmodulin, which is sensitive to extracellular Ca, responsible for the Ca influx in the osteoblast cytoplasm, and in turn governs numerous cellular processes. 66,69…”

Recent advances in regenerative biomaterials

“…While the released ions from metallic biomaterials might be helpful for human body to biological functions, the excessive release of metallic ions is harmful. For example, Mg-related biomaterials can cause side effects such as cytotoxicity [ 56 ]. In addition, it was found that Mg alloy could, by significantly affecting adhesion and migration of endothelial cells (ECs), inhibit the process of re-endothelialization of Mg stents [ 57 ].…”

Chondrogenic primed extracellular vesicles activate miR-455/SOX11/FOXO axis for cartilage regeneration and osteoarthritis treatment

“…Specifically, under the modification of miRNA, BMSCs are able to stably differentiate into chondrocytes and preserve relevant phenotypes, thus having gained much attention in regenerative research recently. Based on previous studies, BMSC-derived EVs have biological functions similar to BMSCs, and play an indispensable role in suppressing inflammation, regulating immune responses, and repairing tissue damage 6 , 16 – 18 . In this way, bioactive molecules contained within EVs could be modified by modulating the state of the donor cells, which makes it possible to engineer EVs derived from preconditioned BMSCs for targeted tissue regeneration in vivo 4 , 19 .…”