Tackling bioactive glass excessive in vitro bioreactivity: Preconditioning approaches for cell culture tests

Abstract

Bioactive glasses (BGs), since their discovery in 1971 by L.L Hench, have been widely used for bone replacement and repair, and, more recently, they are becoming highly attractive for bone and soft tissue engineering applications. BGs have in fact the ability to form a strong bond with both hard and soft tissues once in contact with biological fluid. The enhanced interaction of BGs with the biological environment is based on their significant surface bioreactivity. This surface effect of BGs is, on the other hand, problematic for cell biology studies by standard (static) cell culture methods: an excessive bioreactivity leads in most cases to a rapid and dramatic increase of the pH of the surrounding medium, which results in cell death and makes cell culture tests on BG samples impossible. The BG research community has been aware of this for many years and numerous pre-treatments have been proposed by different groups worldwide to limit this problem. For the first time, we have reviewed in this paper the variety of surface preconditioning treatments that have been put forward over the years, we provide a summary of such pre-treatments used in laboratory practice, discussing and offering criteria that can be used for the determination of the optimal pre-treatment depending on BG composition and morphology of the sample tested (bulk, particulate, scaffolds). The information and discussion provided in this review should support best research practice when testing bioactive glasses in cell culture.

Primary osteoblasts, osteoblast precursor cells or osteoblast‐like cell lines: Which human cell types are (most) suitable for characterizing 45S5‐bioactive glass?

“…The group of Xynos evaluated the impact of 45S5-BG dissolution products on hOBs and found an upregulation of osteogenic gene expression patterns (Xynos et al, 2001). Notably, although 45S5-BG is known to exhibit cytotoxic properties when used in cell culture settings (Ciraldo et al, 2018), viability of hOBs was not significantly altered by 45S5-BG cocultivation. Notably, although 45S5-BG is known to exhibit cytotoxic properties when used in cell culture settings (Ciraldo et al, 2018), viability of hOBs was not significantly altered by 45S5-BG cocultivation.…”

“…Also, the influence of the BGs on the viability of these cells should be evaluated since BGs show excessive initial bioreactivity leading to alterations of the local pH value that might result in damage to the cells, at least in in-vitro settings (Ciraldo, Boccardi, Melli, Westhauser, & Boccaccini, 2018). Cells that are able to differentiate into osteoblasts or are related to the osteogenic lineage should be used in order to assess the influence of the BGs on osteogenic differentiation.…”

“…Cells that are able to differentiate into osteoblasts or are related to the osteogenic lineage should be used in order to assess the influence of the BGs on osteogenic differentiation. Also, the influence of the BGs on the viability of these cells should be evaluated since BGs show excessive initial bioreactivity leading to alterations of the local pH value that might result in damage to the cells, at least in in-vitro settings (Ciraldo, Boccardi, Melli, Westhauser, & Boccaccini, 2018).…”

Enhanced Physiological Stability and Long‐Term Toxicity/Biodegradation In Vitro/In Vivo of Monodispersed Glycerolphosphate‐Functionalized Bioactive Glass Nanoparticles

“…In the structure of silicate glass, SiO 4 tetrahedra is connected through bridging oxygen bond (SiOSi) and the glass structure is altered by metal ions through the nonbridging oxygen bonds (SiOM + ) . Due to the presence of nonbridging oxygen bonds, BGs show typical biodegradation capacity over the time compared with silica and other inorganic nanocrystals . Therefore, BG has been demonstrated as an excellent candidate in osteoblasts differentiation and molecules delivery because of their gene activation properties and guest molecules loading ability…”

Cell Stress Reduction by a Novel Perfusion-Culture System Using Commercial Culture Dish

“…Technologies for cultivating animal cells in vitro (in an artificial environment) are called cell culture techniques [1]. One of the major advantages of cultivating cells in vitro is that one can control the cell culture environment parameters in the physical environment, such as temperature, pH, and shear stress, as well as those in the physiological environment, including hormone or metabolic waste product concentrations [2][3][4][5][6]. In vitro cell culturing also allows researchers to analyze the phenomena of life in an experimental system, which is easier than analyzing cells in vivo [7].…”