Impact of Zinc- or Copper-Doped Mesoporous Bioactive Glass Nanoparticles on the Osteogenic Differentiation and Matrix Formation of Mesenchymal Stromal Cells.

Fabian Westhauser,Simon Decker,Felix Rehder,Qaisar Nawaz,Aldo R Boccaccini,Arash Moghaddam,Elke Kunisch,Sebastian Wilkesmann

doi:10.3390/ma14081864

Abstract

Mesoporous bioactive glass nanoparticles (MBGNs) have gained relevance in bone tissue engineering, especially since they can be used as vectors for therapeutically active ions like zinc (Zn) or copper (Cu). In this study, the osteogenic properties of the ionic dissolution products (IDPs) of undoped MBGNs (composition in mol%: 70 SiO2, 30 CaO) and MBGNs doped with 5 mol% of either Zn (5Zn-MBGNs) or Cu (5Cu-MBGNs; compositions in mol%: 70 SiO2, 25 CaO, 5 ZnO/CuO) on human bone marrow-derived mesenchymal stromal cells were evaluated. Extracellular matrix (ECM) formation and calcification were assessed, as well as the IDPs’ influence on viability, cellular osteogenic differentiation and the expression of genes encoding for relevant members of the ECM. The IDPs of undoped MBGNs and 5Zn-MBGNs had a comparable influence on cell viability, while it was enhanced by IDPs of 5Cu-MBGNs compared to the other MBGNs. IDPs of 5Cu-MBGNs had slightly positive effects on ECM formation and calcification. 5Zn-MBGNs provided the most favorable pro-osteogenic properties since they increased not only cellular osteogenic differentiation and ECM-related gene expression but also ECM formation and calcification significantly. Future studies should analyze other relevant properties of MBGNs, such as their impact on angiogenesis.

Highlights

Mesoporous bioactive glasses have gained relevance in bone tissue engineering (BTE) applications, especially since they can be used as vectors for therapeutically active agents that enhance or modify their intrinsic pro-osteogenic properties [1,2,3]
Cu has pro-angiogenic properties and influences cellular osteogenic differentiation as well as Extracellular matrix (ECM) mineralization in a positive manner [5,6,11,12]. Due to their known beneficial properties, our group recently analyzed the osteogenic properties of sol–gel-derived mesoporous bioactive glass nanoparticles (MBGNs) with a composition of 70 mol% SiO2 and 30 mol% CaO doped with, inter alia, Zn or Cu when cultured in direct contact to human bone marrow-derived mesenchymal stromal cells (BMSCs) [13]
While 5Cu-Mesoporous bioactive glass nanoparticles (MBGNs) showed significantly higher viability than the other MBGNs, ionic dissolution products (IDPs) of the undoped MBGNs and the Zn-doped MBGNs had a comparable influence on the BMSC viability

Summary

Introduction

Mesoporous bioactive glasses have gained relevance in bone tissue engineering (BTE) applications, especially since they can be used as vectors for therapeutically active agents (ions, growth factors, etc.) that enhance or modify their intrinsic pro-osteogenic properties [1,2,3]. The impact of biomaterials, such as MBGNs, on ECM formation and maturation, can be analyzed in cell culture settings using indirect cultivation approaches in which cells are cultivated in the presence of their ionic dissolution products (IDPs) These studies are necessary since direct cultivation settings complicate the assessment of the ECM, especially due to interactions with commonly used assay methods [16,17,18] caused by the intrinsic ability of bioactive glasses (BGs) to develop a carbonate-substituted hydroxyapatite layer on their surface and because BGs stick to their surroundings, to the primitive ECM, in in vitro settings [2,16,19,20]. These surrounding but not directly adjacent cells commit to matrix formation to a relevant extent making analyzing the IDPs’ impact in indirect in vitro settings relevant [22]

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