Toward design of magnetic nanoparticle clusters stabilized by biocompatible diblock copolymers for T2-weighted MRI contrast.

We report the fabrication of magnetic particles comprised of clusters of iron oxide nanoparticles, 7.4 nm mean diameter, stabilized by a biocompatible, amphiphilic diblock copolymer, poly(ethylene oxide-b-D,L-lactide). Particles with quantitative incorporation of up to 40 wt % iron oxide and hydrodynamic sizes in the range of 80-170 nm were prepared. The particles consist of hydrophobically modified iron oxide nanoparticles within the core-forming polylactide block with the poly(ethylene oxide) forming a corona to afford aqueous dispersibility. The transverse relaxivities (r2) increased with average particle size and exceeded 200 s(-1) mM Fe(-1) at 1.4 T and 37 °C for iron oxide loadings above 30 wt %. These experimental relaxivities typically agreed to within 15% with the values predicted using analytical models of transverse relaxivity and cluster (particle core) size distributions derived from cryo-TEM measurements. Our results show that the theoretical models can be used for the rational design of biocompatible MRI contrast agents with tailored compositions and size distributions.

Improved microchip design and application for in situ transmission electron microscopy of macromolecules.

Understanding the fundamental properties of macromolecules has enhanced the development of emerging technologies used to improve biomedical research. Currently, there is a critical need for innovative platforms that can illuminate the function of biomedical reagents in a native environment. To address this need, we have developed an in situ approach to visualize the dynamic behavior of biomedically relevant macromolecules at the nanoscale. Newly designed silicon nitride devices containing integrated "microwells" were used to enclose active macromolecular specimens in liquid for transmission electron microscopy imaging purposes.We were able to successfully examine novel magnetic resonance imaging contrast reagents, micelle suspensions, liposome carrier vehicles, and transcribing viral assemblies. With each specimen tested, the integrated microwells adequately maintained macromolecules in discrete local environments while enabling thin liquid layers to be produced.

Surface cross-linked ultra high molecular weight polyethylene by emulsified diffusion of dicumyl peroxide.

Cross-linking improves the wear resistance of ultrahigh molecular weight polyethylene (UHMWPE) used in hip and knee implants. Free radicals, generated by ionizing radiation or chemically, react to form cross-links. Limiting cross-linking to the articulating surface of the implant is desirable to enable high wear resistance on the surface and higher strength and toughness in the bulk. We investigated the diffusion of emulsified dicumyl peroxide (DCP) into vitamin E-blended UHMWPE (0.1 and 0.3 wt. % vitamin-E) with subsequent thermal decomposition in situ to obtain surface cross-linking with the objective of achieving surface wear rate equivalent or lower than that of current clinically available materials. We diffused emulsified DCP at 100°C followed by in situ decomposition at 150°C. We also assessed the effect of having vitamin-E in the DCP emulsion. The oxidative stability of the treated samples increased with increasing vitamin E concentration in the blend and by incorporating vitamin E into the peroxide emulsion. The impact strength of a surface cross-linked, 0.3 wt% vitamin E blended UHMWPE prepared using this method was superior to a clinically available irradiated and melted highly cross-linked UHMWPE while the wear resistance was comparable. These results showed the feasibility of surface cross-linking using emulsified peroxide diffusion as a method of making tough and wear resistant joint implant bearing surfaces. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1517-1523, 2018.

Peroxide cross-linked UHMWPE blended with vitamin E.

Radiation crosslinked ultrahigh molecular weight polyethylene (UHMWPE) is the bearing surface material most commonly used in total joint arthroplasty because of its excellent wear resistance. Crosslinking agents such as peroxides can also effectively increase wear resistance but peroxide crosslinked UHMWPE has low oxidative stability. We hypothesized that the addition of an antioxidant to peroxide crosslinked UHMWPE could improve its oxidation resistance and result in mechanical, tribological, and oxidative properties equivalent to currently utilized radiation crosslinked UHMWPEs. Various vitamin E (0.1-1.0 wt % and peroxide concentration (0.5-1.5 wt %) combinations were studied to investigate changes in crosslink density, wear rate, mechanical properties, and oxidative stability in comparison to radiation crosslinked UHMWPE. Peroxide crosslinking was more efficient as compared to radiation crosslinking in the presence of vitamin E with the former resulting in lower wear rate with vitamin E concentrations above 0.3 wt %. The tensile mechanical properties were comparable to and the impact strength was higher than those of the clinically relevant radiation crosslinked controls. We also determined that gamma sterilization of peroxide crosslinked vitamin E blends improved wear resistance further. In summary, peroxide crosslinking of vitamin E-blended UHMWPE may provide a feasible and economical alternative to radiation for achieving clinically relevant properties for total joint implants using UHMWPE. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1379-1389, 2017.