LONG TERM BIODEGRADATION OF ELASTOMERS MATERIALS

弹性体材料的长期生物降解

• 批准号: 6526655
• 负责人: P ANNE HILTNER
• 金额: $ 25.34万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-12-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6526655
• 关键词: adsorption; antioxidants; atomic force microscopy; biodegradable product; biomaterial compatibility; biomaterial development /preparation; biomaterial evaluation; biomaterial interface interaction; biotransformation; cell adhesion; cell adhesion molecules; chemical stability; elastomers; human subject; infrared spectrometry; laboratory rat; macrophage; neutrophil; polyurethanes; protein metabolism; scanning electron microscopy; superoxide dismutase

The combination of outstanding chemical and physical properties of polyurethanes (PU's) coupled with their biocompatibility have led to their use in a wide range of biomedical applications. Recent studies have demonstrated the relative lack of in vivo biostability of polyether PU's. In an attempt to improve biostability, alternative PU's have been proposed for biomedical applications. Current studies in our laboratory, directed toward a fundamental understanding of biocompatibility and biostability of PU elastomers, have led to a hypothesis for the cell/polymer feedback control mechanism of in vivo biodegradation. To confirm and/or modify this hypothesis, studies will be carried out on PU's of known composition with and without specific modifications and additives that have been developed to increase the biostability of the PU. The specific aims of the proposed research are: 1. To elucidate the chemical mechanisms by which cellular degrading agents (radicals, HOCl, acid) cause hydrolytic and/or oxidative chain cleavage of polyetherurethanes, polycarbonate urethanes and other PU's with non-polyether soft segments or surface modifying endgroups, (SME's) where the mechanism(s) of biodegradation may be different. Correlative studies will be made with in vitro conditions that mimic the in vivo environment. 2. To characterize the surface degradation of PU's after in vivo and in vitro exposure, and correlate the results with the effect on performance properties. Methods of material characterization will include contact angle, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), Fourier transform infrared (FTIR) spectroscopy (attenuated total reflectance (ATR), micro-ATR, photoacoustic), gel permeation chromatography, and scanning electron microscopy (SEM). 3. To ascertain the effects of stress and strain state on the rate and mechanisms of PU biodegradation. The effects of in vivo and in vitro static strain (uniaxial and biaxal) as well as in vitro cyclic strain (uniaxial and biaxial) will be examined and the results will be correlated with creep as determined in vitro under oxidative and hydrolytic conditions. 4. To determine the effect of PU surface chemistry, SME's, and the effect of additives (superoxide dismutase (SOD) mimics, N-acetyl-cysteine, and modified dehydroepiandrosterone (DHEA)) on the adhesion of monocytes/macrophages and the formation of foreign body giant cells under static and cyclic strain conditions in vitro. These studies will be correlated with in vivo experiments to examine the effects of antioxidants and macrophage inhibitors on biodegradation.

聚氨酯优异的化学和物理性能与它们的生物相容性相结合，使它们在生物医学应用中得到了广泛的应用。最近的研究表明聚醚聚氨酯相对缺乏体内生物稳定性。为了提高生物稳定性，已经提出了用于生物医学应用的替代PU。我们实验室目前的研究旨在对PU弹性体的生物相容性和生物稳定性有一个基本的了解，并提出了细胞/聚合物反馈控制体内生物降解机制的假设。为了证实和/或修改这一假设，将对已知成分的聚氨酯进行研究，包括是否有特定的改性和添加剂，这些改性和添加剂已被开发出来，以提高聚氨酯的生物稳定性。本课题的具体研究目的是：1。阐明细胞降解剂（自由基、HOCl、酸）对具有非聚醚软段或表面修饰端基（SME's）的聚聚氨酯、聚碳酸酯聚氨酯和其他PU的水解和/或氧化链裂解的化学机制，这些PU的生物降解机制可能不同。相关研究将在体外条件下进行，以模拟体内环境。2. 表征聚氨酯在体内和体外暴露后的表面降解，并将结果与对性能的影响联系起来。材料表征的方法将包括接触角、x射线光电子能谱（XPS）、原子力显微镜（AFM）、傅里叶变换红外（FTIR）光谱（衰减全反射（ATR）、微ATR、光声）、凝胶渗透色谱和扫描电子显微镜（SEM）。3. 探讨应力应变状态对聚氨酯生物降解速率和降解机理的影响。将研究体内和体外静态应变（单轴和双轴）以及体外循环应变（单轴和双轴）的影响，并将结果与体外氧化和水解条件下确定的蠕变相关联。4. 在体外静态和循环应变条件下，测定PU表面化学、SME以及添加剂（超氧化物歧化酶（SOD）模拟物、n -乙酰半胱氨酸和改性脱氢表雄酮（DHEA））对单核/巨噬细胞粘附和异物巨细胞形成的影响。这些研究将与体内实验相关联，以检验抗氧化剂和巨噬细胞抑制剂对生物降解的影响。