Development of crosslinkable, thermoplastic polyurethanes for cardiovascular prostheses

[摘要] Existing thermoplastic polyurethanes (TPUs), used in the manufacturing ofcardiovascular devices, still have unproven long-term biostability and may be prone toexcessive plastic deformation when subjected to cyclic loading. These negative aspectscan be attributed to, among other factors, the weak nature of virtual crosslinking throughmicrophase separation. The modification and covalent crosslinking of existing medical gradepolyurethanes with unsaturated acyl chlorides are thus proposed to improve theseproperties.A model compound study was used to find a suitable acyl chloride (4-pentenoylchloride), confirm the intended carbamate nitrogen as successful reaction site and tooptimize the chemistry of the reaction. Two medical grade polyurethanes, Pellethane® 2363-80AE (Pellethane) and PurSil 35-80A (PurSil), were subsequently successfully modifiedwith 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 respectivepolyurethanes.The degree of modification and method of crosslinking were then optimized to obtainthe required mechanical properties (i.e. minimum hysteresis). The hysteresis and creep ofthe 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. Thehysteresis of the crosslinked polymer was at least 27.5% better when compared toPellethane, and showed a significant resistance to surface degradation (as studied withscanning electron microscopy). Although the soft phases in both polyurethanes arevulnerable toward degradation, it was not as pronounced in Pell15.0, mainly due to therestriction of chain movement resulting from the crosslinking.Small-diameter tubular constructs, with similar fiber and wall thicknesses, wereelectrospun from Pellethane and the 15% modified Pellethane. A standard electrospinningtechnique 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 novelmaterial, while simultaneously forming the tubular constructs.It is suggested that the manufacturing of Pell15.0 be scaled up to produce adequateamounts 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 andfurther optimize the electrospun tubular constructs.

[发布机构] Stellenbosch University