In vitro evaluation of orthopedic composite cytotoxicity: Assessing the potential for postsurgical production of hydroxyl radicals

Abstract

Hydroxyl radical (⅐OH)-induced inflammation is a primary mode for in vivo cytotoxicity. A legitimate concern is whether particulate wear debris from orthopedic composites can stimulate inflammation via ferrous ion (Fe 2؉ )-mediated production of ⅐OH. The purpose of this research was to utilize electron paramagnetic resonance (EPR) spin trapping in investigating and comparing the potential for postsurgical cytotoxicity induced specifically by ⅐OH in the presence of two composites: Simplex P and the novel, hybrid, CORTOSS™. Cytotoxicity is evaluated based on the composites competitively chelating catalytic Fe 2؉ or readily reducing ferric ions (Fe 3؉ ), in facilitating the Fenton reaction (FR). ⅐OH that are produced were then validated by a radical scavenger to confirm a genuine radical signal and mechanism. Spin adduct peak areas decreased in the presence of CORTOSS as opposed to increasing in the presence of Simplex P, evaluated against their respective controls. A plausible theory elucidating this finding is that CORTOSS may sequester the Fe form, by virtue of its monomers. Principally, direct comparison of composites indicated that Simplex P had greater tendency to produce ⅐OH, yielding 25.6 and 48.7% greater spin adduct peak areas when chelated and non-chelated Fe 2؉ are used, respectively. Moreover, the rate of FR accelerated when chelated Fe 2؉ was used, leading to the formation of a ternary complex with the composites. This was more prominent in Simplex P, as coordination of chelated Fe 2؉ occurs on its surface via an electrostatic attraction to allow a seventh coordination site for ligand exchange in the ternary complex, stabilized by Ba 2؉ . Conversely, the silica found in CORTOSS possesses radical quenching abilities that deactivate generated ⅐OH in impeding the efficiency of FR. Neither composite demonstrated a capacity to readily reduce Fe 3؉ to the relevant Fe 2؉ , as validated by a non-radical pathway. Instead, the artificial spin adduct signal attained when employing chelated Fe 3؉ was due to the nucleophilic addition of water onto DMPO. Simplex P may also serve as a template for surface catalysis of the nucleophilic addition of water onto DMPO involving chelated Fe 3؉ . CORTOSS is thought not to induce cytotoxicity, whereas the propensity of Simplex P in promoting Fenton chemistry is a serious issue that must be addressed.

Osteointegration of a Bisphenol-a-Glycidyl-Dimethacrylate Composite and Its Use in Anterior Skull Base Defects

“…Interestingly, Cortoss was found to be like a free radical scavenger, an important feature of this material. 24 We have to underline that bis-GMA-based allograft may not be suitable in cases of very large bone defects. Glass ionomer cement proposed by Helms and Geyer 11 was stated to be available for shaping outside the body before application and hardening, thus allowing to obtain a material to fit exactly to a large bone defect.…”

Acrylic Bone Cements: The Role of Nanotechnology in Improving Osteointegration and Tunable Mechanical Properties

“…They combined a biodegradable polymer (PHB or PHBV) with bioactive glass filler as silicate-based glass or borate-based glass. [42,49,50] Pure PMMA cement and those containing PHB and PHBV, were assayed for cell viability/proliferation (MTT assay) in cells of human bone marrow, under conditions that promoted osteoblastic differentiation, 62 for twenty one days. Results are shown in Figure 2, they indicated that PHBV containing cements had improved performance.…”

Bone substitutes in the Netherlands – A systematic literature review

“…Cortoss Ò has osteoconductive properties [139], but is not resorbed [140]. It does not induce cytotoxicity [141], and offers biocompatibility and reduced risk of thermal necrosis [142].…”