Cytocompatibility of Potential Bioactive Cerium-Doped Glasses based on 45S5

Abstract

The cytocompatibility of potential bioactive cerium-containing (Ce3+/Ce4+) glasses is here investigated by preparing three different glasses with increasing amount of doping CeO2 (1.2, 3.6 and 5.3 mol% of CeO2, called BG_1.2, BG_3.6 and BG_5.3, respectively) based on 45S5 Bioglass® (called BG). These materials were characterized by Environmental Scanning Electron Microscopy (ESEM) and infrared spectroscopy (FTIR) after performing bioactivity tests in Dulbecco’s Modified Eagle Medium (DMEM) solution, and the ions released in solution were determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and Optical Emission Spectrometry (ICP-OES). The data obtained clearly show that the glass surfaces of BG, BG_1.2 and BG_3.6 were covered by hydroxyapatite (HA), while BG_5.3 favored the formation of a cerium phosphate crystal phase. The cytotoxicity tests were performed using both murine long bone osteocyte-like (MLO-Y4) and mouse embryonic fibroblast (NIH/3T3) cell lines. The cerium-containing bioactive glasses show an increment in cell viability with respect to BG, and at long times, no cell aggregation and deformation were observed. The proliferation of NIH/3T3 cells increased with the cerium content in the glasses; in particular, BG_3.6 and BG_5.3 showed a higher proliferation of cells than the negative control. These results highlight and enforce the proposal of cerium-doped bioactive glasses as a new class of biomaterials for hard-tissue applications.

Cell Proliferation to Evaluate Preliminarily the Presence of Enduring Self-Regenerative Antioxidant Activity in Cerium Doped Bioactive Glasses

“…In the first use, the optical density (O.D.) expressed as a percentage respect to BG (100.00%) is higher for BG_5.3 (91.43%) after 24 h, while a greater cell expansion is detected for BG_1.2 (104.66%) after 72 h. The best performance of BG_5.3 is detected after 24 h; we actually confirmed the lower NR cell uptake at a longer time (72 h) as observed in our previous paper [48]. In the second use, BG_5.3 reveals a cell viability higher than BG, both at 24 and 72 h (102.27% and 103.12%, respectively) suggesting a higher uptake and a positive effect of cerium.…”

“…The results of MTT tests are reported in Figure 2a-e. All cerium-doped glasses, at the first use, favor the viability of MLO-Y4 cells both after 24 h (112.98%, 125.43%, 137.36%) and 72 h (111.02%, 107.41%, 105,23%) respectively for BG_1.2, BG_3.6 and BG_5.3, as observed previously [48]. After 24 h, the results of the second use are consistent with those of the first use; on the contrary, at 72h we detected an unequivocal decrease in cell viability (55.67%, 59.06%, 61.74% respectively for BG_1.2, BG_3.6 and BG_5.3).…”

“…After 24 h, the results of the second use are consistent with those of the first use; on the contrary, at 72h we detected an unequivocal decrease in cell viability (55.67%, 59.06%, 61.74% respectively for BG_1.2, BG_3.6 and BG_5.3). In summary, we can assert that in the first use, the cerium-containing glasses, in comparison with BG, positively influenced the proliferation of MLOY4 cells after 24 h in MTT (112.99%-137.36%) and BrdU (106.64%-130.08%) assays; the latter was also proved in our previous study [48]. These results changed significantly in the second use; in fact, after 24 h, all doped glasses (BG_1.2, BG_3.6 and BG_5.3) gave rise to a lower cell viability (61.60%-89.85%) in comparison with BG by means of BrdU assay.…”

“…Recently, we have studied the biocompatibility of 45S5Bioglass ® doped with an increasing amount of CeO 2 (1.2 mol%, 3.6 mol% and 5.3 mol%), soaked in (Dulbecco's Modified Eagle Medium) DMEM for different times and tested in a cell culture medium with osteocyte-like murine long bone (MLO-Y4) and mouse embryonic fibroblast (NIH/3T3) cell lines [48]; these cellular types are particularly informative for investigation on bone substitutes [49].…”

Comparison of the Influence of 45S5 and Cu-Containing 45S5 Bioactive Glass (BG) on the Biological Properties of Novel Polyhydroxyalkanoate (PHA)/BG Composites

“…The 45S5 BG is in general bioactive, biocompatible, biodegradable, osteoconductive, osteoinductive, angiogenic, nontoxic and noninflammatory because of its ability to form a hydroxycarbonate apatite surface layer in a biological medium and exploiting the release of ionic dissolution products that stimulate specific cellular pathways [24][25][26][27][28][29]. Since the release of ionic dissolution products, after exposure to a physiological environment, is believed to improve the bioactivity of materials, new approaches for enhancing BG bioactivity are being investigated by introducing therapeutic ions in BG compositions [30][31][32]. In this work, Cu-doped BG was used as an example of the use of inorganic ions to further enhance the bioactivity of PHAs.…”