Regulation of smooth muscle cell adhesion, proliferation, and motility on biomaterials is critical to the performance of blood-contacting implants and vascular tissue engineering scaffolds. The goal of this study was to examine the underlying substrate-smooth muscle cell response relations, using a selection of polymers representative of an expansive library of multifunctional, tyrosine-derived polycarbonates. Three chemical components within the polymer structure were selectively varied through copolymerization: (1) the content of iodinated tyrosine to achieve X-ray visibility; (2) the content of poly(ethylene glycol) (PEG) to decrease protein adsorption and cell adhesivity; and (3) the content of desaminotyrosyl-tyrosine (DT), which regulates the rate of polymer degradation. Using quartz crystal microbalance with dissipation, we quantified differential serum protein adsorption behavior because of the chemical components DT, iodinated tyrosine, and PEG: increased PEG content within the polymer structure progressively decreased protein adsorption but the simultaneous presence of both DT and iodinated tyrosine reversed the effects of PEG. The complex interplay of these components was next tested on the adhesion, proliferation, and motility behavior cultured human aortic smooth muscle cells. The incorporation of PEG into the polymer reduced cell attachment, which was reversed in the presence of iodinated tyrosine. Further, we found that as little as 10% DT content was sufficient to negate the PEG effect in polymers containing iodinated tyrosine, whereas in non-iodinated polymers, the PEG effect on cell attachment was reversed. Cross-functional analysis of motility and proliferation revealed divergent substrate chemistry related cell response regimes. For instance, within the series of polymers containing both iodinated tyrosine and 10% of DT, increasing PEG levels lowered smooth muscle cell motility without a change in the rate of cell proliferation. In contrast, for non-iodinated tyrosine and 10% of DT, increasing PEG levels increased cell proliferation significantly while reducing cell motility. Clearly, the polycarbonate polymer library offers a sensitive platform to modulate cell adhesion, proliferation, and motility responses, which, in turn, may have implications for controlling vascular remodeling in vivo. Additionally, our data suggests unique biorelevant properties following the incorporation of iodinated subunits in a polymeric biomaterial as a potential platform for X-ray visible devices.

Intro: We have developed the novel concept of using ePTFE vascular graft material as an underlying form for development of a scaffold. This scaffold is created by coating ePTFE with bioresorbable tyrosine-derived polycarbonates while maintaining porosity, but limiting exposure of the ePTFE to blood. We have developed a poly(ethylene glycol) (PEG)-containing, tyrosine-derived polycarbonate by copolymerizing DTE with 2.5% PEG (Mw= 2000) to obtain poly(DTE-co-2.5%PEG2k carbonate). The inhibitory effect of PEG on protein adsorption and cell adhesion has been established. This study was done to develop a porous scaffold for use in vascular applications and test the ability of this polymer to decrease thrombogenicity in a rat model. Methods: ePTFE was coated in a solution containing a specific concentration (0, 2, 4, 7, 10 and 15%) of polymer. The completeness of the coating was determined by SEM, and confocal microscopy of samples coated with fluorescent dye doped polymer. XPS spectra were acquired to observe changes in coating completeness as a function of polymer concentration. The ratio of % atomic concentrations of Fl to C were obtained, since the DTE contains no fluorine. Evaluation of thrombosis using an in vivo rat model was performed. Elliptical shaped patches (5 mm x 3 mm) of ePTFE were coated in 7% solutions of DTE, DTE-PEG, or uncoated ePTFE. An arteriotomy was made in the abdominal aorta of heparinized Sprague Dawley rats and a patch was sutured to the aorta. The rats were observed under anesthesia after restoration of blood flow and patency confirmed by Doppler. After 30 min, the segment of aorta containing the patch was removed. The aorta was opened longitudinally on the opposite side from the patch for imaging. A thrombosis score (0-5) was used to determine amount of clot present on the patch. Statistical differences among groups were determined by ANOVA with post-hoc comparison. Results: Increasing concentration of polymer used to coat the ePTFE resulted in visible changes by SEM with the nodes and fibrils appearing thicker with porosity maintained.