Attenuation of Cellular Inflammation Using Glucocorticoid-Functionalized Copolymers

This work has demonstrated the functionalization of an amphiphilic diblock copolymer, comprised of polyethylene oxide-polymethyl methacrylate (PEO-PMMA), as well as a triblock copolymer comprised of polymethyloxazoline-polydimethylsiloxane-polymethyloxazoline(PMOXA-PDMS-PM OXA) with the dexamethasone (Dex) glucocorticoid anti-inflammatory. Interfacial deposition of the copolymer and the Dex molecules and subsequent transfer of the hybrid materials to solid substrates were characterized to evaluate the potential of utilizing this composite material as a suppressor of cyto-inflammation to enhance implant biocompatibility. Given the extremely thin dimensions of the film (~4nm), this material would have negligible impact upon the size of the coated device to preclude biological stress. The composite films were interfaced with the RAW264.7 murine macrophages which served as a model cell line for the evaluation of nuclear factor-kappaB (NF-KB)-induced production of a host of inflammatory cytokines including interleukin-6, interleukin-12, tumor necrosis factor-alpha (TNFalpha), as well as the inducible nitric oxide synthase signaling factor which is known to be involved with stress-related processes such as neuronal damage. Lipopolysaccharide or LPS is a component of bacterial membranes that elicits cellular stress following application to RAW cell cultures. Following the induced stress response, significant reductions in the expression of genes associated with the aforementioned cytokines and signaling molecules indicated that macrophages in direct contact with the functionalized copolymer were able to collect Dex that was released from within the polymer network to attenuate cyto-inflammation mechanisms. This composite membrane represents a medically-relevant technology to promote chronic implant functionality and preclusion of bio-fouling.