Michael DiCicco, Ryan Compton, Susan A Jansen-Varnum

Abstract. Hydroxyl radical (^-OH)-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 (Fe²⁺)-mediated production of ^-OH. 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 ^-OH in the presence of two composites: Simplex P, and the novel, hybrid, CORTOSS^TM. Cytotoxicity is evaluated based on the composites competitively chelating catalytic Fe²⁺ or readily reducing ferric ions (Fe³⁺), in facilitating the Fenton reaction (FR). ^-OH 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 ^-OH, yielding 25.6 and 48.7% greater spin adduct peak areas when chelated and non-chelated Fe²⁺ are used, respectively. Moreover, the rate of FR accelerated when chelated Fe²⁺ was used, leading to the formation of a ternary complex with the composites. This was more prominent in Simplex P, as coordination of chelated Fe²⁺ occurs on its surface via an electrostatic attraction to allow a seventh coordination site for ligand exchange in the ternary complex, stabilized by Ba²⁺. Conversely, the silica found in CORTOSS possesses radical quenching abilities that deactivate generated ^-OH in impeding the efficiency of FR. Neither composite demonstrated a capacity to readily reduce Fe³⁺ to the relevant Fe²⁺, as validated by a non-radical pathway. Instead, the artificial spin adduct signal attained when employing chelated Fe³⁺ 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 Fe³⁺. 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..