(627f) Polymer Chemistry and Device Geometry Control in Vitro Activation of Dendritic Cells

Polyanhydrides are biodegradable polymers with excellent biocompatibility and have shown much promise as drug/vaccine delivery vehicles. In vaccine delivery applications, a heightened immune response is desirable whereas low immune reactions are preferred for multi-component implants. To investigate the adjuvant effect of polyanhydrides we employed a combinatorial approach to rapidly assess activation of murine dendritic cells (DCs) by polyanhydrides composed of sebacic acid (SA) and 1,6-bis(p-carboxyphenoxy)hexane (CPH). Libraries of films and nanospheres of six varying CPH:SA chemistries were incubated with the DCs for 48 h, after which supernatants were collected to assess cytokine production and the cells were stained for evaluation of cell surface marker expression. This data was analyzed by principal component analysis, which rapidly uncovered underlying trends and activation ?hot spots'. The copolymer chemistry was demonstrated to control the expression of MHC II, CD86, CD40, and CD209, with SA-rich chemistries best promoting up-regulation of these markers. On the other hand the CPH-rich chemistries were the most successful at promoting the production of the cytokines, IL-6 and IL-12p40, from the DCs. Although chemistry-related trends were observed for both device geometries, the nanosphere libraries demonstrated a higher level of DC activation than the film libraries with greater expression of all cell surface markers tested and higher production of IL-12p40. However, IL-6 was produced at higher levels with the polymer film libraries. Cellular internalization is known to occur with particles less than 10 μm in diameter. Thus, the activation of DCs treated with the CPH:SA nanospheres is most likely a direct result of particle internalization. However, it is known that IL-6 production occurs independent of phagocytosis, which may explain the increased IL-6 production by cells treated with the film libraries. The adjuvant effect demonstrated by the CPH:SA nanosphere library makes it a promising platform for vaccine delivery. On the other hand, the extracellular surface-surface interaction between the DCs and the polymer films is likely insufficient for production of a heightened immune response, which is a desirable attribute for tissue engineered implants. This rapid investigation of cell-material interactions paves the way for rational design and optimization of biomaterials for drug/vaccine delivery and tissue engineering.