Polyurethane Biomaterials with Heparin Binding Sites

描述（由申请人提供）：众所周知，高分子生物材料的抗血栓性可以通过肝素的表面端点固定来改善。目前的肝素化方法是复杂和昂贵的，并可能降低基础聚合物的机械性能。拟议的研究将确定合成具有“内置”肝素结合位点的坚韧热塑性聚氨酯生物材料的可行性。肝素化将通过简单地将由主题聚合物制成的设备/组件浸泡在水肝素溶液中来实现。二胺-二胺-二醇（PIME）具有与肝素结合的既定能力，将在已建立的生物医学聚碳酸酯-聚氨酯中取代一些正常的二醇“扩链剂”。所得到的含pime聚氨酯的表面将通过和频率产生光谱（SFG），接触角测量学和原子力显微镜进行表征。肝素活性将通过激活部分血栓形成时间（APTT）对新合成和灭菌的器械类似物进行测定。初步结果表明，用SFG可以很容易地将表面聚丙烯酸甲酯与基体聚氨酯区分开来。此外，非无菌含PIME的肝素化聚氨酯的APTT为bb50 500秒，而不含PIME的聚氨酯的APTT <55秒。对肝素具有内在亲和力的生物材料将降低表面肝素化的成本，因此适用于广泛的血液接触医疗设备和假体。

DESCRIPTION (provided by applicant):It is well known that the thrombo-resistance of polymeric biomaterials can be improved by surface endpoint immobilization of heparin. Current heparinization methods are complex and costly, and may degrade the mechanical properties of the base polymer. The proposed study will determine the feasibility of synthesizing tough, thermoplastic polyurethane biomaterials with 'built-in' binding sites for heparin. Heparinization will be achieved by simply soaking the device/component made from the subject polymer, in an aqueous heparin solution. A diamine-diamide-diol (PIME), which has an established ability to bind heparin, will replace some of the normal diol 'chain extender' in a well-established biomedical polycarbonate-urethane. Surfaces of the resulting PIME-containing polyurethanes will be characterized by Sum Frequency Generation Spectroscopy (SFG), Contact Angle Goniometry, and Atomic Force Microscopy. Heparin activity will be determined by Activated Partial Thromboplastic Time (APTT) on freshly synthesized and sterilized device analogues. Preliminary results indicate surface PIME can be easily distinguished from the base polyurethane by SFG. Also, non-sterile heparinized PIME-containing polyurethanes exhibit an APTT of >500 seconds compared to <55 seconds for polyurethanes without PIME. Biomaterials with inherent affinity for heparin will reduce the cost of surface heparinization and are therefore applicable to a wide range of blood-contact medical devices and prostheses.