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The use of dense CO2 in polymer processing can provide a response to the need for more environmentally-friendly industrial processes. Products with high-purity, sterility, and porosity can be achieved using dense gas technology (DGT). Currently, DGT has been used in different aspects of polymer processing including polymerization, micronization, and impregnation. Due to its solubility in polymers, CO2 can penetrate and plasticize polymers, while impregnating them with low-molecular weight CO2 -soluble compounds. Biodegradable polymers and other medical-grade polymers have benefited from the application of DGT. Dense CO2 processing properties of inertness, non-toxicity, and affinity for various therapeutic compounds are specifically advantageous to the medical and biomedical industries. In this work, the different applications of DGT in polymer processing are revised, then implemented. The polymerization of polycarbonate (PC) and polycaprolactone (PCL) in dense CO2 are presented. The syntheses of both polymers were successful and were aided by the use of dense CO2 . A multi-stage approach using dense CO2 as a sweep fluid to extract the PC polymerization by-product phenol is reported. Polycaprolactone was synthesized with varying temperatures and dense CO pressures, then impregnated with a CO2 -soluble therapeutic agent. The impregnated PCL acted as a drug reservoir with a drug-loading of 27wt% and a sustained drug release profile was observed for all samples over several days. Polymer blends of PC/PCL have potential industrial and biomedical applications both in vivo and in vitro. The applicability of PCL can be extended by enhancing its mechanical properties by creating a bio-blend with a stronger polymer such as PC. In this work, PC/PCL nonporous and porous blends were produced. Three novel dense CO2 blending techniques were used. The macroporous PC/PCL blend was impregnated with a therapeutic agent using CO2 as the carrier. A drug loading of 20wt% was achieved and sustained drug release was observed over 3 days. The applicability of dense CO2 in polymer processing was further demonstrated by sterilizing macroporous PC/PCL blends and soft hydrogels with dense CO2 . The PC/PCL blends and hydrogels were inoculated with vegetative bacteria and bacterial endospores. Industrial standard sterilization levels were achieved.

Cellular interactions which occur at tissue implant interfaces may determine the biocompatibility of implanted devices. These studies investigate the macrophage and its products, which are hypothesized to be partially responsible for the long term biocompatibility of implanted materials. Alterations in the production of cytokines and growth factors IL-1-B, IL-1-A, TNF-A, TGF-A, TGF-B and IL-6 by activated monocytes in response to biomedical polymers were evaluated. The polymers were studied with or without preadsorbed human blood proteins IgG, fibrinogen, fibronectin, hemoglobin and albumin due to the initial protein adsorption event upon implantation of foreign materials in vivo. The biomedical polymers Biomer, Polyethylene, Polydimethylsiloxane, expanded Polytetrafluoroethylene and Dacron were selected due to their current medical application. These studies utilized two different controls to evaluate the data: nonprotein preadsorbed polymers and tissue culture treated polystyrene due to the nature of the in vitro assay system. The results of these studies show that there was a polymer and protein dependent alteration in the activity of activated monocytes/macrophages at the surface of bio medical polymers determined by alterations in monocyte secretion of IL-1-B, TGF-A and IL-6. The production of TNF-A, TGFB and IL-1-A was similar for all polymer and protein combinations. Down regulation of functional IL-1 activity was observed when protein preadsorbed polymers were compared to the protein preadsorbed polystyrene. Enhancement in functional IL-1 activity was observed when the polymers were compared to their respective nonprotein preadsorbed polymer controls. The monocyte culture supernatants stimulated fibroblast proliferation in a protein and polymer dependent manner. This suggests that certain polymers and adsorbed proteins may result in decreased fibroblast proliferation which may be important when considering fibroplasia, wound healing and tissue encapsulation of implanted materials. These studies showed that activated monocytes/macrophages are altered by protein preadsorbed biomedical polymers. Alterations in monocyte activity appeared to be dependent on the polymer, adsorbed protein and cytokine evaluated. These studies support the proposed multidimensional events which occur at tissue implant interfaces in vivo

Cellular, humoral, and bacterial interactions with biomedical polymers were studied under static and flow conditions using in vitro techniques. Static studies quantified in vitro endothelial cell attachment and proliferation as well as protein adsorption on polymethacrylate additive modified poly(ether urethane urea) (PEUU) films. Electron spectroscopy for chemical analysis showed additives to be surface active in the unhydrated state. Contact angle analysis suggested that, in water, hydrophilic additives at the interface rapidly reorient to expose hydrophilic moieties. Hydrophobic additives at the PEUU interface were displaced by the more hydrophilic PEUU chains and these films behaved similarly to unloaded films. Increased interfacial hydrophilicity caused by some of the additives correlated with enhanced protein adsorption and endothelial cell behavior on PEUU films. New additives were designed to increase interfacial hydrophilicity, and these additives often exhibited significantly better protein and endothelial cell behavior than did the polymethacrylate additives. Whole human blood, injected or preseeded with Staphyloccocus epidermidis, and cardiovascular materials were used in a recirculating system to address the questions of bacterial adhesion and persistence on biomater ials under flow conditions. Slime and non-slime forming S. epidermidis adhered avidly to nonsmooth materials. Protein adsorption levels in the presence of injected S. epidermidis correlated inversely to S. epidermidis adherence, implying that adherent bacteria block adsorbed proteins. Protein adsorption levels were highest on preseeded materials which adhered the highest numbers of bacteria. At least 70% of the bacteria on preseeded materials embolized during recirculation with human blood, implying that adsorption of proteins occurred to a remaining bacterial biofilm on the material. Whole blood white cell depletion and plasma C3a and fibrinopeptide A elevation in recirculated blood were largely independent of test conditions in the presence of bacteria. Conversely, whole blood platelet depletions and plasma thrombospondin concentrations were often significantly higher for respective materials in the presence of injected, slime forming S. epidermidis than for other bacterial conditions. Preseeded and injected slime and non-slime forming S. epidermidis activated humoral and cellular defense mechanisms, albeit to different degrees. These studies indicate that S. epidermidis meet two criteria of infection, bacterial adhesion and persistence, under all bacterial test conditions and for all materials tested.