DEVCELOPMENT OF POLYURETHANES WITH ENHANCED BIOSTABILITY

开发具有增强生物稳定性的聚氨酯

• 批准号: 6258300
• 负责人: JOHN V MCLUSKY
• 金额: $ 14.87万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-09-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6258300
• 关键词: biomaterial compatibility; biomaterial development /preparation; biomaterial evaluation; biotransformation; chemical stability; chemical structure function; elastomers; high performance liquid chromatography; infrared spectrometry; laboratory rat; molecular site; nuclear magnetic resonance spectroscopy; physical property; polyurethanes; technology /technique development

Polyurethane (PU) elastomers have excellent mechanical properties and high blood and tissue compatibility. They are widely used in biological implants ranging from catheters to artificial heart valves Their use in long-term implantation is unsatisfactory due to biologically induced hydrolysis and enzymatic and oxidative degradation. Attention has focused on the flexible soft segments and the right hard domains as prime factors in determining a PU's biostability. Ether-based soft segments undergo slow oxidation and subsequent chain cleavage, while some aliphatic soft segments undergo slow oxidation and subsequent chain cleavage, while some aliphatic soft segments become oxidatively crosslinked and brittle. The polymer's hard domains inhibit degradation by shielding the urethane linkages from hydrolysis. Numerous studies have investigated PU biostability, unfortunately both their typically narrow scope and their minimal ability to control hard domain morphology have made it virtually impossible to uncover the complex interrelationships between hard domains, soft segments, and biostability. The objective of this study is to develop polyurethane elastomers with maximal biostability. Three aspects of this study will contribute dramatically to its success. First is the invention by the PI of technology to control the phase separation (and thereby physical properties) of PU elastomers independent to the hydrophobicity of the polyurethane soft segment. Second, the new technology allows the use of statistically designed experimental protocols to model the effect each chemical and morphological change has on polymer biostability. The experiments will also determine the interactions between these variables. The models will enable finer control of hard domain formation and, thereby, polymer physical properties and biostability. Also a very wide range of PU precursors will be used to guarantee that all polymer subtypes are tested. Finally, a solid-state NMR, DMA, and IR spectroscopy (among others) will enable testing of hypotheses concerning the role each chemical change has on the polymer morphology and biostability The Specific Aims are: 1. Use model compounds to confirm the sites which are susceptible to biological attack and identify the degradation products. 2. Investigate how the new technology modifies phase separation within PU polymers, and determine phase characteristics of maximally biostable polymers. 3. Use statistically designed experiments to investigate the interplay between the polymers' chemical functionality, hydrophobicity, morphology, crosslink density on polymer stability in vitro. 4. Develop maximally biostable polyurethane elastomers; measure success using in vitro degradation protocols. 5. Bring the most promising elastomers through small animal in vivo stability studies to test and refine the hypotheses.

聚氨酯（PU）弹性体具有优异的机械性能和较高的血液和组织相容性。它们广泛应用于从导管到人造心脏瓣膜等生物植入物中。由于生物诱导的水解以及酶促和氧化降解，它们在长期植入中的使用并不令人满意。人们的注意力集中在灵活的软链段和正确的硬链段上，它们是决定聚氨酯生物稳定性的主要因素。醚基软链段经历缓慢氧化和随后的链断裂，而一些脂肪族软链段经历缓慢氧化和随后的链断裂，而一些脂肪族软链段变得氧化交联和脆化。该聚合物的硬域通过保护氨基甲酸酯键免于水解来抑制降解。许多研究都调查了 PU 的生物稳定性，不幸的是，它们通常范围狭窄，而且控制硬域形态的能力极低，使得几乎不可能揭示硬域、软链段和生物稳定性之间复杂的相互关系。本研究的目的是开发具有最大生物稳定性的聚氨酯弹性体。这项研究的三个方面将对其成功做出巨大贡献。首先是通过 PI 技术发明来控制 PU 弹性体的相分离（从而控制物理性能），而与聚氨酯软链段的疏水性无关。其次，新技术允许使用统计设计的实验方案来模拟每种化学和形态变化对聚合物生物稳定性的影响。实验还将确定这些变量之间的相互作用。该模型将能够更好地控制硬域的形成，从而控制聚合物的物理性能和生物稳定性。此外，还将使用非常广泛的聚氨酯前体来保证所有聚合物亚型都经过测试。最后，固态 NMR、DMA 和红外光谱（以及其他）将能够测试有关每种化学变化对聚合物形态和生物稳定性的作用的假设。具体目标是： 1. 使用模型化合物来确认发生化学变化的位点。容易受到生物攻击并识别降解产物。 2. 研究新技术如何改变 PU 聚合物内的相分离，并确定最大生物稳定性聚合物的相特征。 3. 使用统计设计的实验来研究聚合物的化学功能、疏水性、形态、交联密度之间的相互作用对聚合物体外稳定性的影响。 4、开发最大生物稳定性聚氨酯弹性体；使用体外降解方案衡量成功程度。 5. 通过小动物体内稳定性研究引入最有前途的弹性体来测试和完善假设。