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Despite the technological improvements in orthopedic joint replacement implants, wear and corrosion products associated with the metal components of these implants may result in adverse local tissue and perhaps systemic reactions and toxicities. The current review encompasses a literature review of the local and systemic toxicity studies concerning the effect of CoCrMo wear debris released from wear and corrosion of orthopedic implants and prostheses. Release of metallic debris is mainly in the form of micro- and nano-particles, ions of different valences, and oxides composed of Co and Cr. Though these substances alter human biology, their direct effects of these substances on specific tissue types remain poorly understood. This may partially be the consequence of the multivariate research methodologies employed, leading to inconsistent reports. This review proposes the importance of developing new and more appropriate in-vitro methodologies to study the cellular responses and toxicity mediated by joint replacement wear debris in-vivo.

Cellular internalization and trans-barrier transport of nanoparticles can be manipulated on the basis of the physicochemical and mechanical characteristics of nanoparticles. Research has shown that these factors significantly influence the uptake of nanoparticles. Dictating these characteristics allows for the control of the rate and extent of cellular uptake, as well as delivering the drug-loaded nanosystem intra-cellularly, which is imperative for drugs that require a specific cellular level to exert their effects. Additionally, physicochemical characteristics of the nanoparticles should be optimal for the nanosystem to bypass the natural restricting phenomena of the body and act therapeutically at the targeted site. The factors at the focal point of emerging smart nanomedicines include nanoparticle size, surface charge, shape, hydrophobicity, surface chemistry, and even protein and ligand conjugates. Hence, this review discusses the mechanism of internalization of nanoparticles and ideal nanoparticle characteristics that allow them to evade the biological barriers in order to achieve optimal cellular uptake in different organ systems. Identifying these parameters assists with the progression of nanomedicine as an outstanding vector of pharmaceuticals.

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Peripheral nerve regeneration strategies employ the use of polymeric engineered nerve conduits encompassed with components of a delivery system. This allows for the controlled and sustained release of neurotrophic growth factors for the enhancement of the innate regenerative capacity of the injured nerves. This review article focuses on the delivery of neurotrophic factors (NTFs) and the importance of the parameters that control release kinetics in the delivery of optimal quantities of NTFs for improved therapeutic effect and prevention of dose dumping. Studies utilizing various controlled-release strategies, in attempt to obtain ideal release kinetics, have been reviewed in this paper. Release strategies discussed include affinity-based models, crosslinking techniques, and layer-by-layer technologies. Currently available synthetic hollow nerve conduits, an alternative to the nerve autografts, have proven to be successful in the bridging and regeneration of primarily the short transected nerve gaps in several patient cases. However, current research emphasizes on the development of more advanced nerve conduits able to simulate the effectiveness of the autograft which includes, in particular, the ability to deliver growth factors.

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Corrosion at modular junctions of total hip replacement (THR) remains a major concern today. Multiple types of damage modes have been identified at modular junctions, correlated with different corrosion characteristics that may eventually lead to implant failure. Recently, within the head-taper region of the CoCrMo retrieval implants, cell-like features and trails of etching patterns were observed that could potentially be linked to the involvement of cells of the periprosthetic region. However, there is no experimental evidence to corroborate this phenomenon. Therefore, we aimed to study the potential role of periprosthetic cell types on corrosion of CoCrMo alloy under different culture conditions, including the presence of CoCrMo wear debris. Cells were incubated with and without CoCrMo wear debris (obtained from a hip simulator) with an average particle size of 119 ± 138 nm. Electrochemical impedance spectroscopy (EIS) was used to evaluate the corrosion tendency, corrosion rate, and corrosion kinetics using the media after 24 h of cell culture as the electrolyte. Results of the study showed that there was lower corrosion resistance (p < 0.02) and higher capacitance (p < 0.05) within cell media from macrophages challenged with particles when compared with the other media conditions studied. The potentiodynamic results were also in agreement with the EIS values, showing significantly higher corrosion tendency (low E corr ) (p < 0.0001) and high I corr (p < 0.05) in media from challenged macrophages compared with media with H 2 O 2 solution. Overall, the study provides in vitro experimental evidence for the possible role of macrophages in altering the chemical environment within the crevice and thereby accelerating corrosion of CoCrMo alloy.

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