Nano-osteoimmunology as an important consideration in the design of future implants

Abstract

The size of wear particles emanating from a prosthesis at interfaces is critical to the interfacial properties of the joint replacement and responses from the biological environment. Nanoscale particles in particular require investigation. This project aimed to evaluate the osteoimmunological response to nanoscale ultrahigh molecular weight polyethylene (UHMWPE) wear particles in vitro, including dendritic cells (DCs), macrophages, osteoclasts (OCs), cytokine secretion, and co-cultured OCs and osteoblasts (OBs). The wear particles generated from a constant-load knee prosthesis actuator were profiled using atomic force microscopy and fractionated into sizes of 0.05-0.2, 0.2-0.8, 0.8-1, 1-5 and 5-10 μm. The fractions were exposed to DCs isolated from mice spleen, human OCs, and co-cultured human OBs and OCs, and the effects of the particles on the cells were determined. Results revealed that exposure to nanoscale UHMWPE wear particles induced significant DC activation (p<0.05) and consequently increased cytokine interleukin (IL)-6 and IL-1β secretion (p<0.05). Exposure to nanoscale particles promoted OC maturation, resulting in the suppression of OB proliferation in OB and OC co-cultures. Therefore, the results of this study could contribute to a more mechanistic understanding of wear-debris-associated prosthesis failure. Furthermore, nanoscale UHMWPE wear particles should be considered as mediators of periprosthetic inflammation in the future development of biomaterials for joint replacement bearing surfaces.