The development and characterization of degradable, segmented polyurethanes containing amino acid-based chain extenders

grantor: University of TorontoDegradable segmented polyurethanes were attained through the incorporation of experimental amino acid-based (L-phenylalanine and L-lysine), ester containing chain extenders. The phenylalanine-based chain extender was synthesized and purified to a good final yield (~45%). A protected form of L-lysine (N-[epsilon]-carbobenzoxy-L-lysine) was used to avoid unwanted crosslinking reactions during polymerization. Difficulties with low yield (~1%) and incomplete diesterification of the lysine-based chain extender were mitigated by alteration of the linking diol chemistry. A low toxicity L-lysine-based diisocyanate (2,6-diisocyanato methyl caproate, LDI) was used to synthesize the degradable polyurethanes. The effect of soft segment type (polycaprolactone diol, PCL and polyethylene oxide, PEO) and chain extender type and content on physicochemical properties was evaluated. The polymers ranged from completely amorphous to semicrystalline. Tensile strengths varied from 1.0 to 30.8 MPa. Bulk hydrophilicity ranged from water soluble to 1.3% water uptake, depending primarily on soft segment chemistry and content. Generally, the PEO-containing polyurethanes were weak, hydrophilic materials while the PCL polyurethanes were strong, hydrophobic elastomers. The carbobenzoxy (CBZ) protecting group of the L-lysine ester chain extended polyurethane was removed by hydrogenolysis. Nuclear magnetic resonance spectroscopic analysis indicated that deprotection resulted in a 37 mol% reduction in CBZ content. However, deprotection resulted in backbone urethane cleavage leading to reduced molecular weight and loss of hard segment. The 'in vitro' degradation properties of the polyurethanes were studied in buffer and enzyme solutions to evaluate the susceptibility to passive and enzymatic hydrolysis, respectively. Inclusion of amino acid-based chain extenders conferred enhanced susceptibility towards enzymatic attack by two model enzymes (chymotrypsin and trypsin) and increasing chain extender content led to increasing enzymatic erosion. Enzymatic degradation and erosion proceeded via a surface-limited mechanism, causing little change in bulk properties. The magnitude of erosion was enzyme-dependent, making it possible to tune erosion based on the enzyme profile at the application site. Lastly, the 'in vitro' cytocompatibility of the polyurethane degradation products generated during buffer incubation was evaluated by MTT assay. The polyurethane degradation products were not found to elicit a significant cytotoxic response (