Over the last five years, several structurally new polymers derived from amino acids and dipeptides [pseudopoly(amino acids)] were synthesized. Among those polymers, the tyrosine-derived polycarbonates were identified as promising candidates for biomaterials development since they have favorable engineering properties, degrade under physiological conditions, and produce a mild foreign body response upon implantation in several animal models. However, detailed information about physicomechanical properties, correlations between chemical structure and polymer properties, cell-polymer interactions, surface properties, degradation mechanism and the toxicological properties of the degradation products is still missing. As a bridge between the previous synthetic phase of our studies and the possible development of specific medical implants, a three-year, detailed investigation of tyrosine-derived polycarbonates is proposed. This investigation has five main goals: l. Determination of the physicomechanical and thermal properties, including the engineering properties relevant to potential biomedical applications. 2. Exploration of the feasibility of performing controlled surface modifications. The existing pendent chains of tyrosine-derived polycarbonates will be used for the generation of controlled amounts of free carboxylic acid groups and amino groups on the polymer surface. 3. Study of the cell-polymer interactions in an attempt to elucidate possible correlations between polymer structure and surface chemistry, and the biological response. Devices with carefully characterized surface and bulk properties will be used in in vitro cell attachment and growth studies and in vivo investigations of the inflammatory response using the air-pouch technique. 4. Elucidation of the rate and mechanism of polymer degradation. Based on the currently proposed degradation mechanism, four likely degradation products have been identified. These compounds will be synthesized in pure form and will serve as model compounds in the further investigation of the degradation mechanism. These studies will also explore possible autocatalytic effects and the possible use of excipients to modify the polymer degradation rate. 5. Biomaterials screening assays. Using ASTM protocols, the polymer and its degradation products will be evaluated. Biomaterials screening tests include evaluations of hard and soft tissue compatibility, cytotoxicity of polymer and polymer degradation products, and an evaluation of sterilizability. Upon successful completion of this research program, it will be possible to better assess the potential utility of tyrosine-derived polycarbonates as medical implant materials. Considering the urgent need to provide the medical device community with new alternatives to the ubiquitous poky(lactic acid) and poly(glycolic acid), the development of new, degradable implant materials has been recognized as an important research challenge.
