Development of crosslinkable, thermoplastic polyurethanes for cardiovascular prostheses
Thesis (PhD (Process Engineering))--University of Stellenbosch, 2006.
Existing thermoplastic polyurethanes (TPUs), used in the manufacturing of cardiovascular devices, still have unproven long-term biostability and may be prone to excessive plastic deformation when subjected to cyclic loading. These negative aspects can be attributed to, among other factors, the weak nature of virtual crosslinking through microphase separation. The modification and covalent crosslinking of existing medical grade polyurethanes with unsaturated acyl chlorides are thus proposed to improve these properties. A model compound study was used to find a suitable acyl chloride (4-pentenoyl chloride), confirm the intended carbamate nitrogen as successful reaction site and to optimize the chemistry of the reaction. Two medical grade polyurethanes, Pellethane® 2363- 80AE (Pellethane) and PurSil 35-80A (PurSil), were subsequently successfully modified with 4-pentenoyl chloride. The degree of modification could be accurately controlled (R2 = 0.99) to between 4.5% to 20.0% and between 11.5% to 18.5% for the respective polyurethanes. The degree of modification and method of crosslinking were then optimized to obtain the required mechanical properties (i.e. minimum hysteresis). The hysteresis and creep of the modified and crosslinked Pellethane were reduced by 42.5% and 44.0%, respectively, while the hysteresis of the modified and crosslinked PurSil was reduced by 12.9%. The chemical stability of Pellethane (control) modified Pellethane (15% modification) and crosslinked Pellethane (Pell15.0) was evaluated in an in vitro degradation study. The hysteresis of the crosslinked polymer was at least 27.5% better when compared to Pellethane, and showed a significant resistance to surface degradation (as studied with scanning electron microscopy). Although the soft phases in both polyurethanes are vulnerable toward degradation, it was not as pronounced in Pell15.0, mainly due to the restriction of chain movement resulting from the crosslinking. Small-diameter tubular constructs, with similar fiber and wall thicknesses, were electrospun from Pellethane and the 15% modified Pellethane. A standard electrospinning technique was used in the case of the former while in the case of the latter a novel “reactive” electrospinning technique was used for the in situ crosslinking of the novel material, while simultaneously forming the tubular constructs. It is suggested that the manufacturing of Pell15.0 be scaled up to produce adequate amounts of material to enable the extrusion and in vivo evaluation of e.g. pacemaker leads. A circulatory animal model, e.g. a senescent baboon model, could be used to evaluate and further optimize the electrospun tubular constructs.