Do total hip arthroplasty polyethylene liners without free radicals oxidize in vivo or ex vivo?

Crosslinking substantially reduces the wear of ultra-high molecular weight polyethylene (UHMWPE) used in total hip arthroplasty (THA) but some reports have indicated that first generation liners manufactured without antioxidants may be vulnerable to in vivo oxidation. This study evaluated maximum oxidation using Fourier transform infrared spectroscopy per ASTM F2102-06ε1 and linear head penetration using a coordinate measuring machine among 66 revision-retrieved THA components with in vivo durations ranging from 0.02 to 24.6 years. These included 30 liners crosslinked with 5 Mrad of gamma radiation and then melted, 13 non-crosslinked, never-irradiated liners sterilized with gas plasma and 23 non-crosslinked, never-irradiated liners sterilized with ethylene oxide. All liners were vacuum-sealed and stored at -20°C prior to analysis with the exception of three retrievals of each material type that were stored in air for 9.9 to 21.5 years. All 57 vacuum-sealed and frozen retrievals demonstrated good oxidative stability with maximum oxidation indices (OIs) less than 1.0 and 75% (43/57) of these liners had maximum OIs less than 0.1. Linear penetration measurements were lower in the crosslinked liners compared to non-crosslinked retrievals. Although instances of oxidation and embrittlement were found after ex vivo storage in air among liners that did not have free radicals at the time of implantation, in vivo oxidation does not appear to be a clinical concern through the first decade of service for crosslinked liners and at up to 25 years after surgery for non-crosslinked liners.

In Vivo Oxidative Stability Changes of Highly Cross-Linked Polyethylene Bearings: An Ex Vivo Investigation.

The development of highly cross-linked UHMWPEs focused on stabilizing radiation-induced free radicals as the sole precursor to oxidative degradation. However, secondary in vivo oxidation mechanisms have been discovered. After a preliminary post-operative analysis, we subjected highly cross-linked retrievals with 1-4 years in vivo durations and never-implanted controls to accelerated aging to predict the extent to which their oxidative stability was compromised in vivo. Lipid absorption, oxidation, and hydroperoxides were measured using infrared spectroscopy. Gravimetric swelling was used to measure cross-link density. After aging, all retrievals, except vitamin E-stabilized components, regardless of initial lipid levels or oxidation, showed significant oxidative degradation, demonstrated by subsurface oxidative peaks, increased hydroperoxides and decreased cross-link density, compared to their post-operative material properties and never-implanted counterparts, confirming oxidative stability changes.

Thermosensitive liposomes modified with poly(N-isopropylacrylamide-co-propylacrylic acid) copolymers for triggered release of doxorubicin.

A novel polymer-modified thermosensitive liposome (pTSL) was developed for the delivery of Doxorubicin (DOX) for cancer therapy. Copolymers containing temperature-responsive N-isopropylacrylamide (NIPAAm) and pH-responsive propylacrylic acid (PAA) were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, yielding copolymers with dual pH/temperature-dependent phase transition properties. When attached to liposomes, these copolymers were membrane-disruptive in a pH/temperature-dependent manner. pTSL demonstrated enhanced release profile and significantly lower thermal dose threshold when compared to traditional thermosensitive formulations and were stable in serum with minimal drug leakage over time. These liposomes thus have the potential to dramatically reduce the risk of damage to healthy tissues that is normally associated with liposomal cancer therapy.