Periodic microstructures on bioactive glass surfaces enhance osteogenic differentiation of human mesenchymal stromal cells and promote osteoclastogenesis in vitro.

Bioactive glasses (BG) are known for their ability to bond to hard and soft tissues. We hypothesized that the stimulation of bone remodeling, including cellular bone forming and bone resorbing processes, can be increased by applying periodic microstructures on the glass surfaces in vitro. To test our hypothesis, two different BG (45S5 and 13-93) were microstructured in a groove-and-ridge pattern of different sizes by a novel casting process and tested in cell culture experiments using human mesenchymal stromal cells (hMSCs) and RAW 264.7 cells. The microstructures induced contact guidance of hMSCs and increased osteogenic marker gene expression of the stem cells, compared to non-structured glass surfaces as verified by ELISA and quantitative real-time PCR (qPCR) analyses. Furthermore, the structures stimulated the differentiation of RAW cells to osteoclast-like cells confirmed by TRAP gene expression and their resorption activity causing visible resorption lacunae. Our results demonstrate that periodically microstructured BG (especially 45S5) might improve the osteogenic differentiation of hMSCs and influence the activity of material resorbing cells in vitro. Hence, microstructuring of BG could enhance the remodeling process of bone substitutes critical for the formation of new bone tissue in vivo and thus be used to trigger bone remodeling kinetics in vivo. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1965-1978, 2018.

Response of umbilical cord mesenchymal stromal cells to varying titanium topographical signals.

A wide variety of titanium implant modifications have been developed to improve tissue- or cell-material interactions including bone bonding, implant failure, and contact osteogenesis. Osteogenesis can be stimulated by mechanobiological signals such as topography though translation of in vivo reactions to in vitro bioactivity and stem cell culture data, and vice versa, is challenging. We hypothesized that a systematic in vitro approach comparing clinically well-accepted implant surface topographical modifications could shed light on potential cell biological mechanisms provoked by submicron-, micron- or macrostructured surfaces. In this study, we investigated the response of umbilical cord derived mesenchymal stromal cells (UC-MSCs) to anodized, particle blasted, and plasma sprayed highly porous Plasmapore surfaces, which is known to promote bony ingrowth in vivo. After 21 days, UC-MSCs undergo a morphological shift from a 2D to 3D behavior on micro- or macrostructures visualized by actin-vinculin fluorescence and are able to fill the porous surfaces completely. Cell viability after 7 days was significantly decreased on the micro- and macrostructured surfaces particle blasted and Plasmapore, compared to polished controls. The analysis of osteogenic differentiation under noninduced conditions revealed a significantly elevated ALP activity on Plasmapore, indicating a beneficial effect of this macrostructured surface toward osteogenic differentiation supported by late elevated gene expression of osteopontin evaluated by qPCR. Mineralization as well as in vitro bioactivity was pronounced on anodized surfaces. Our findings point to synergistic implant modification strategies allowing early contact osteogenesis and bone ingrowth for future implant designs. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 180-191, 2018.

Mimicking physiological flow conditions to study alterations of bioactive glass surfaces in vitro.

Bioactive glasses form a strong bond with surrounding tissue and slowly degrade when implanted in vivo, stimulating the host bone to regenerate itself. We investigated the behaviour of microstructured bioactive glass surfaces (13-93) in an SBF reactor, which mimics physiological flow conditions. The structures were developed to potentially influence cell-biological long term processes such as osteogenic differentiation. It is therefore important that the structures withstand a certain time in SBF or body fluids. The experiments revealed that these structures were preserved up to 30 days. Although macroscopically stable, mass loss under flowing conditions was 2-2.5%, in contrast to <1% under static conditions. Polished samples in flowing medium lost 2.7% up to day 7 and then regained mass, resulting in overall 0.5% mass loss after 30 days. Thicker calcium phosphate rich layers for the samples in flowing medium were detected, demonstrating better bone bonding capacity than predicted conventionally. The hydroxyapatite conversion in the reactor was comparable to published in vivo data. We conclude that surface alterations that occur in vivo can be better mimicked by using the proposed flow bioreactor than by the established SBF method in static medium. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 228-236, 2018.