Injectable β -TCP/MCPM cement associated with mesoporous silica for bone regeneration: characterization and toxicity evaluation

Abstract

Calcium phosphate cement has been widely investigated as a bone graft substitute due to its excellent self-setting ability, biocompatibility, osteoconductivity and moldability. In addition, mesoporous materials have been studied as potential materials for application in medical devices due to their large surface area, which is capable of loading numerous biological molecules, besides being bioactive. In this study, bone β-TCP-MCPM-based injectable cement with mesoporous silica particles was synthesized and characterized in terms of its mechanical properties, microstructure, porosity, injectability, in vitro bioactivity and degradability; together with toxicity effects in CHO-K1 cell culture. The results showed that the β-TCP-MCPM cement is bioactive after soaking in simulated body fluid solution, and mesoporous silica particles provided better physicochemical properties compared with silica-free cement. Toxicity assays showed low CHO-K1 cell viability after treatment with more concentrated extracts (200 mg ml). However, this behavior did not compromise the reproductive capacity and did not promote significant DNA damage in those cells. In conclusion, the β-TCP-MCPM cement associated with mesoporous silica might be considered as a potential bone substitute for the repair and regeneration of bone defects.

Effects of Silicon Compounds on Biomineralization, Osteogenesis, and Hard Tissue Formation

“…Mesoporous silica particles provided better physicochemical properties compared to silica-free cements. For example, toxicity assays showed low Chinese hamster ovary (CHO)-K1 cell viability after treatment with more concentrated extracts (200 mg mL −1 ) [133].…”

Injectable bone cements: What benefits the combination of calcium phosphates and bioactive glasses could bring?

“…In the end, incorporation of BG within CaP/PLGA composites modulated the pH at physiological level during the composite degradation process. Summarizing the findings above, it should be considered that for BG incorporated CPC composites higher degradation rates will be observed, if compared with pure CPC, mainly due to the relatively high BG solubility [ 116 , 117 , [121] , [122] , [123] , [124] , [125] , 129 , 130 ]. It can be also inferred that the degradation rate can be effectively controlled by the weight fraction and composition of BG incorporated in the CPC.…”

“…El-Fiqi et al [ 119 ] pointed out that the higher surface area of mesoporous BG particles, which also contributes to an increased overall surface area of the BG incorporated CPC, leads to the formation of microspherical apatite islands on the surface of BG incorporated CPC composites, that facilitates protein adsorption (Cytochrome C (Cyto.c) was used as model protein), if compared to pure CPC [ 119 ]. Mendes et al [ 122 ] incorporated mesoporous particles into brushitic cement and a needle-like crystal morphology after 7 days of incubation in SBF solution at 37 °C was observed. After 14 days of incubation, the presence of the particles was no longer detected by using energy-dispersive spectroscopy (EDS) analysis.…”

“…Besides the close relationship between the ion release and pH changes, also the degradation of the composites is strongly affected by the pH variations and these two parameters have a reciprocal relationship as well. For example, the degradation of β-TCP from the mesoporous silica incorporated CPC composites of Mendes et al [ 122 ] reduced the pH of the surrounding medium from pH 7.4 to pH 6.0, and then the pH was stabilized when the DCPD crystals and the remaining β-TCP equilibrated. BG incorporated CaP/PLGA composites reported by Renno et al [ 116 ] revealed a pH decrease during the 9 weeks of incubation in PBS at 37 °C.…”

“…The formed hydroxyapatite (HAp)-like layer following the (partial) dissolution of BG incorporated CPC has a leading role in creating a strong bond to bone, stimulating osteoblast cell proliferation and differentiation, inducing angiogenesis and presenting antibacterial effects [ 123 , 137 , 138 ]. Indirect cell culture techniques in which the cells are exposed to the extracted medium of the incubated samples revealed that the dissolution products of BG incorporated injectable CaP cement composites are responsible for changes in cellular activity [ 121 , 122 , 125 ]. A cytotoxic effect of high concentration extracts (200 mg/ml) of both CaP cements and BG incorporated CaP cements was determined in the study of Mendes et al [ 122 ] by using Chinese hamster ovary cells (CHO–K1).…”