A NOVEL APPROACH TO NONTHROMBOGENIC POLYMER SURFACES

非血栓形成聚合物表面的新方法

• 批准号: 3336089
• 负责人: SUNG WAN KIM
• 金额: $ 13.55万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-12-01 至 1991-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3336089
• 关键词: adenine nucleotides; affinity chromatography; antithrombogenic surface; arteriovenous shunt surgery; biomaterial evaluation; biomaterial interface interaction; bradykinin; cardiovascular prosthesis; cardiovascular surgery; catheterization; cell adhesion; chemical conjugate; coagulation factor X; crosslink; dogs; electron microscopy; heparin; ion exchange chromatography; kallikreins; laboratory rabbit; particle; platelet aggregation inhibitors; platelet factor 4; polyethylenes; polymers; polyurethanes; prostaglandin E; radioimmunoassay; radiotracer; scintillation counter; thrombin; thromboplastin; thrombopoiesis; tissue /cell culture; ultrafiltration

Heparin releasing and immobilized polymers have demonstrated a significant reduction in thrombus formation on the blood/polymer interface. In vitro studies revealed that prevention of fibrin formation using the designed systems were mainly due to heparin activity, in terms of APTT, TT, and anti- Factor Xa tests. In vivo studies of heparin immobilized surfaces displayed minimum fibrin formation, although platelet adhesion was not significantly reduced. In this application, both commercial and fractionated heparin will be immobilized onto a model surface (Sepharose 6B) and a practical surface (polyurethane) using both hydrophilic and polar spacer arm groups. Based on our previous studies it is expected that the hydrophilic environment of the block spacer interface will reduce protein adsorption and subsequent platelet adhesion. Heparin-PGE1 conjugate will also be immobilized on the surface by similar chemistry to achieve the dual pharmacological actions of reducing fibrin formation and inhibiting platelet adhesion. The experimental parameters, hydrophilic environment via hydrophilic spacer groups, heparin activity, and a heparin-PGE1 conjugate, will be investigated by utilizing a design variable of differing spacer group lengths between the surface and immobilized heparin or heparin-PGE1 conjugate. The animal experiments include rabbit ex vivo shunt (short term) catheter implant (short term) and vascular implant in dogs (long term). The results of the experimental data will verify possible mechanisms involved in thrombus formation (role of adsorbed protein, clotting factors, and platelet interaction) and provide a more effective model for the design of a blood compatible polymer surface. This will eliminate the need or systemic administration of anticoagulants in patients using blood contacting medical devices.

肝素释放和固定化聚合物已经证明 血栓的形成显著减少。 血液/聚合物界面。体外研究表明， 使用所设计的系统防止纤维蛋白的形成 主要是由于肝素的活性，在APTT，TT和抗- 因子Xa检验。肝素固定化表面的体内研究 显示最低限度的纤维蛋白形成，尽管血小板粘连 没有明显减少。 在此应用中，商业肝素和分级肝素 将被固定在模型表面(Sepharose6B)上，并且 使用亲水性和极性的实用表面(聚氨酯) 间隔臂组。根据我们之前的研究，预计 嵌段间隔物界面的亲水环境 会减少蛋白质吸附和随后的血小板黏附。 肝素-前列腺素E_1结合物也将被固定在表面 通过相似的化学作用实现药理作用的双重 减少纤维蛋白形成和抑制血小板黏附。 实验参数、亲水环境通过 亲水性间隔基、肝素活性和肝素-PGE1 共轭，将通过利用设计变量 表面和之间的间隔基团长度不同 固定化肝素或肝素-前列腺素E_1结合物。这只动物 实验包括兔体外分流(短期)导管 犬植入(短期)和血管植入(长期)。 实验数据的结果将验证这一可能性 血栓形成的机制(吸附的作用 蛋白质、凝血因子和血小板相互作用)，并提供 设计一种更有效的血液兼容模型 聚合物表面。这将不再需要或系统性 用血患者的抗凝剂应用 接触医疗设备。