SURFACE STRUCTURE & BLOOD COMPATIBILITY OF POLYURETHANES

表面结构

• 批准号: 2215938
• 负责人: Buddy D Ratner
• 金额: $ 12.04万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2215938
• 关键词: adsorption; albumins; atomic force microscopy; biomaterial development /preparation; biomaterial evaluation; biomaterial interface interaction; biotransformation; calcification; chemical structure; fibrinogen; fluorocarbon polymers; human tissue; hydrocarbons; infrared spectrometry; interferometry; phosphorus; platelet activation; polyurethanes; scanning electron microscopy; surface property

The applications of polyurethanes in medicine continue to increase. Advantages cited for polyurethanes include excellent mechanical properties, blood compatibility, and biostability. While these advantages are extolled by some researchers, serious shortcomings in both blood compatibility and biostability have been identified for conventional segmented block copolyurethanes (PEUs). This credibility gap can, we believe, be largely attributed to non-standardized or poorly designed test methods. We have recently found a high platelet reactivity for conventional PEUs and found that many surface chemical functionalities of conventional PEUs are susceptible to degradation by agents similar to those found in the inflammatory sequence. We have recently synthesized PEUs with surface structures dominated by hydrocarbon moieties that show extremely low platelet reactivity, and may be resistant to biodegradation and calcification. This proposal is directed towards the development and evaluation of PEUs with improved blood compatibility under arterial, flow conditions, and enhanced resistance to biodegradation and calcification compared with conventional PEUs. Therefore, five research components are necessary. Synthesis: New PEUs with high, stable surface concentrations of hydrocarbon and fluorocarbon groups will be synthesized. We hypothesize that these surface layers protect the polymer from degradation, reduce calcification sites, and impart low platelet reactivity. Characterization: PEUs will be extensively characterized using the resources of the National ESCA and Surface Analysis Center for Biomedical Problems. Biodegradation: The susceptibility of the PEUs to oxidative and enzymatic attack will be assessed in vitro and in rat implant studies. Blood Compatibility: The good performance of hydrocarbon surface-enriched PEUs is believed to be associated with high albumin affinity. Protein adsorption studies will evaluate the ability of the PEUs to selectively adsorb albumin from plasma and measure the surface albumin retention strength. The adsorption, retention, and immunologic recognizability of fibrinogen to these polyurethanes will also be explored since these factors have been associated with platelet reactivity. A new circulating loop blood compatibility model that can measure four classes of interactions between platelets and surfaces will be used to assess blood compatibility. Results will be compared to chronic in vivo canine studies (AV shunt). Calcification: The susceptibility of the PEUs to calcification in an unstrained and strained state will be assessed in vitro. Given the high blood reactivity and biostability problems often observed for the conventional, commercial PEUs (Biomer, Biolon, Pellethane) that have dominated blood contact device development, the demise of commercial sources for these polymers may be beneficial to progress. This research points the way to a new generation of PEUs that might exhibit excellent blood compatibility in the arterial tree.

聚氨酯在医学上的应用不断增加。 聚氨酯的优点包括优异的机械性能， 性能、血液相容性和生物稳定性。虽然这些优势 被一些研究人员颂扬，这两种血液的严重缺陷 已经确定了常规的生物相容性和生物稳定性， 嵌段共聚物（PEU）。这种信任的差距，我们 我认为，这主要归因于非标准化或设计不良的测试 方法.我们最近发现， 传统的PEU，并发现许多表面化学功能的 传统的PEU容易被类似于 那些在炎症序列中发现的。 我们最近合成了具有以下表面结构的PEU： 显示极低血小板反应性的烃部分，并且可以 抗生物降解和钙化。这项建议是 旨在发展和评价PEU， 动脉、流动条件下的血液相容性，以及增强的 与传统的抗生物降解和抗钙化性相比， PEU。因此，需要五个研究组成部分。合成：新 具有高的、稳定的碳氢化合物表面浓度的PEU， 将合成氟碳基团。我们假设这些表面 层保护聚合物免于降解，减少钙化部位， 并赋予低血小板反应性。表征：PEU将 利用国家ESCA的资源， 生物医学问题表面分析中心。生物降解： PEU对氧化和酶攻击的敏感性将是 在体外和大鼠植入研究中进行评估。血液相容性： 烃表面富集的PEU的良好性能被认为是 与高白蛋白亲和力相关。蛋白质吸附研究将 评价PEU从血浆中选择性吸附白蛋白的能力 并测量表面白蛋白保留强度。吸附， 保留，以及纤维蛋白原对这些 聚氨酯也将被探索，因为这些因素已经被 与血小板反应性有关。一种新的循环回路血液 兼容性模型，可以衡量四类之间的相互作用 血小板和表面将用于评估血液相容性。结果 将与慢性体内犬研究（AV分流）进行比较。 钙化：PEU对钙化的敏感性， 将在体外评估未应变和应变状态。 鉴于经常观察到的高血液反应性和生物稳定性问题， 对于常规的商业PEU（Biomer、Biolon、Pellethane）， 已经主导了血液接触设备的发展，商业的消亡， 这些聚合物的来源可能有利于进步。本研究 指出了新一代PEU的发展方向， 动脉树的血液相容性。