Ionic dissolution products of Cerium-doped bioactive glass nanoparticles promote cellular osteogenic differentiation and extracellular matrix formation of human bone marrow derived mesenchymal stromal cells

Biomed Mater. 2021 Mar 5;16(3). doi: 10.1088/1748-605X/abcf5f.

Abstract

Cerium (Ce) is a promising candidate ion for application in bone tissue engineering (BTE) since it reduces the presence of reactive oxygen species. Ce-doped mesoporous bioactive glass nanoparticles (MBGNs) serving as vectors for the local application of Ce already demonstrated stimulating effects on the expression of pro-osteogenic genes in Saos-2 cells. So far, there is no evidence available about the effects of Ce-doped MBGNs on the viability, osteogenic differentiation and the formation of the osseous extracellular matrix (ECM) of primary human bone marrow-derived mesenchymal stromal cells (BMSCs). Therefore, in this study, the biocompatibility of the ionic dissolution products (IDPs) of MBGNs containing increasing concentrations of CeO2(0.05 MCe-MBGNs, composition in mol%: 86.6SiO2-12.1CaO-1.3CeO2; and 0.2 MCe-MBGNs, composition in mol%: 86.0SiO2-11.8CaO-2.2CeO2) and unmodified MBGNs (composition in mol%: 86SiO2-14CaO) was evaluated using human BMSCs. Eventually, the impact of the MBGNs' IDPs on the cellular osteogenic differentiation and their ability to build and mature a primitive osseous ECM was assessed. The Ce-doped MBGNs had a positive influence on the viability and stimulated the cellular osteogenic differentiation of human BMSCs evaluated by analyzing the activity of alkaline phosphate as a marker enzyme for osteoblasts in the present setting. Furthermore, the formation and calcification of a primitive osseous ECM was significantly stimulated in the presence of Ce-doped MBGNs in a positive concentration-dependent manner as demonstrated by an elevated presence of collagen and increased ECM calcification. The results of thisin-vitrostudy show that Ce-doped MBGNs are attractive candidates for further application in BTE.

Keywords: bone tissue engineering; cerium; extracellular matrix; human mesenchymal stromal cells; mesoporous bioactive glass nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biocompatible Materials* / chemistry
  • Biocompatible Materials* / pharmacology
  • Bone and Bones / cytology
  • Bone and Bones / metabolism
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Cerium* / chemistry
  • Cerium* / metabolism
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Glass / chemistry
  • Humans
  • Male
  • Mesenchymal Stem Cells* / cytology
  • Mesenchymal Stem Cells* / drug effects
  • Nanoparticles* / chemistry
  • Nanoparticles* / metabolism
  • Osteogenesis / drug effects*
  • Tissue Engineering / methods
  • Young Adult

Substances

  • Biocompatible Materials
  • Cerium