Off-Stoichiometric Reactions at the Cell–Substrate Biomolecular Interface of Biomaterials: In Situ and Ex Situ Monitoring of Cell Proliferation, Differentiation, and Bone Tissue Formation

Abstract

The availability of osteoinductive biomaterials has encouraged new therapies in bone regeneration and has potentially triggered paradigmatic shifts in the development of new implants in orthopedics and dentistry. Among several available synthetic biomaterials, bioceramics have gained attention for their ability to induce mesenchymal cell differentiation and successive bone formation when implanted in the human body. However, there is currently a lack of understanding regarding the fundamental biochemical mechanisms by which these materials can induce bone formation. Phenomenological studies of retrievals have clarified the final effect of bone formation, but have left the chemical interactions at the cell–material interface uncharted. Accordingly, the knowledge of the intrinsic material properties relevant for osteoblastogenesis and osteoinduction remains incomplete. Here, we systematically monitored in vitro the chemistry of mesenchymal cell metabolism and the ionic exchanges during osteoblastogenesis on selected substrates through conventional biological assays as well as via in situ and ex situ spectroscopic techniques. Accordingly, the chemical behavior of different bioceramic substrates during their interactions with mesenchymal cells could be unfolded and compared with that of biomedical titanium alloy. Our goal was to clarify the cascade of chemical equations behind the biological processes that govern osteoblastogenic effects on different biomaterial substrates.

Osteogenic Enhancement of Zirconia-Toughened Alumina with Silicon Nitride and Bioglass®

“…The consequent (exogenous) development of ROS at the biomolecular cell/substrate interface probably irreversibly damages proteins and nucleic acids, and causes peroxidation of membrane lipids, ultimately leading to cell apoptosis [16]. This hypothesized mechanism of action is consistent with previously published data showing no cell proliferation and osteogenesis inhibition on Al 2 O 3 surfaces [35].…”

“…Post-mortem analyses identified Al 3+ ions at the interface between non-mineralized and mineralized bone; these ions reduced osteoblastic activity, induced apoptosis, and discouraged bone remodeling [17,34]. We recently compared in vitro osteoblastogenesis of mesenchymal cells cultured on Al 2 O 3 versus other biomaterial substrates [35]. Raman spectral changes suggested a common apoptotic mechanism in cells exposed to Ti6Al4V alloy and Al 2 O 3 substrates with intracellular biochemical changes consistent with toxicity [36].…”

Mechanisms of instantaneous inactivation of SARS-CoV-2 by silicon nitride bioceramic

“…Si 3 N 4 has been used for more than 15 years in the human body in contact with bone and soft tissue without any adverse effect being so far reported. 86 Moreover, several in vitro studies have shown the compatibility of Si 3 N 4 with different cells lines, including mature osteoblasts, 87 mesenchymal cells, 4 , 88 , 89 and primary odontoblasts. 90 As a fine micrometric powder, Si 3 N 4 can remain suspended in the air for some period, but its effect on human health is comparable to inert dust.…”

Raman Analyses of Laser Irradiation-Induced Microstructural Variations in Synthetic Hydroxyapatite and Human Teeth

“…To quantitatively analyze the effects of laser irradiation on HAp structures, in this study, laser irradiation experiments were carried out on two types of hydroxyapatite ceramics and two human teeth at different powers, and the structural variations of HAp in these samples after laser irradiation were investigated by Raman microprobe spectroscopy. Raman spectroscopy is effective in evaluating and mapping material microstructural and stoichiometric alterations according to the change in the spectral morphology [ 16 , 17 , 18 ], and in this study, the spectral bandwidth of the crystalline phase and the relative intensities associated with defect and amorphous structures of HAp were observed to exhibit clear variations at the irradiated locations as a function of the laser power. The results revealed that the HAp microstructure showed a significant dependence on laser power as well as on the initial degree of the stoichiometry of the materials.…”