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LONG TERM BIODEGRADATION OF ELASTOMERS MATERIALS

弹性体材料的长期生物降解

基本信息

批准号：
6662524
负责人：
P ANNE HILTNER
金额：
$ 26.09万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1979
资助国家：
美国
起止时间：
1979-12-01 至 2005-08-31
项目状态：
已结题

项目摘要

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（PU）优异的化学和物理性能与其生物相容性相结合，使其在广泛的生物医学应用中得到应用。最近的研究已经证明聚醚PU的体内生物稳定性相对缺乏。为了改善生物稳定性，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，针对PU弹性体的生物相容性和生物稳定性的基本理解，导致了体内生物降解的细胞/聚合物反馈控制机制的假设。为了证实和/或修改这一假设，将对已知组成的PU进行研究，这些PU具有和不具有特定的修改和添加剂，这些修改和添加剂已被开发用于增加PU的生物稳定性。本研究的具体目的是：1.阐明细胞降解剂（自由基、HOCl、酸）导致聚醚醚酮、聚碳酸酯聚醚醚酮和其他具有非聚醚软链段或表面改性端基的PU（SME）水解和/或氧化链断裂的化学机制，其中生物降解机制可能不同。将在模拟体内环境的体外条件下进行相关研究。2.表征PU在体内和体外暴露后的表面降解，并将结果与对性能特性的影响相关联。材料表征方法包括接触角、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）、凝胶渗透色谱法和扫描电子显微镜（SEM）。3.探讨应力应变状态对PU生物降解速率的影响及其机理。将检查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，并将结果与氧化和水解条件下体外测定的蠕变相关。4.确定PU表面化学、SME和添加剂（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））对体外静态和循环应变条件下单核细胞/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，以检查抗氧化剂和巨噬细胞抑制剂对生物降解的影响。