LONG TERM BIODEGRADATION OF ELASTOMERS MATERIALS

聚氨酯(PU‘s)优异的化学和物理性能与其生物相容性相结合，使其在生物医学领域得到了广泛的应用。最近的研究表明，聚醚PU的体内生物稳定性相对较差。为了提高生物稳定性，人们提出了替代PU的生物医学应用。我们实验室目前的研究旨在从根本上了解PU弹性体的生物相容性和生物稳定性，从而产生了体内生物降解的细胞/聚合物反馈控制机制的假说。为了证实和/或修正这一假设，将对已知组成的PU进行研究，其中包括已开发的用于提高PU生物稳定性的特定修饰和添加剂。1.阐明细胞降解剂(自由基、高氯酸、酸)引起含非聚醚软段或表面修饰端基的聚醚、聚碳酸酯和其他PU的水解链和/或氧化链断裂的化学机理(S)可能是不同的生物降解机理。相关研究将在模拟体内环境的体外条件下进行。2.表征PU在体内和体外暴露后的表面降解情况，并将结果与其对性能的影响进行关联。材料表征的方法包括接触角、X射线光电子能谱(XPS)、原子力显微镜(AFM)、傅立叶变换红外光谱(FTIR)光谱(衰减全反射(ATR)、显微全反射(ATR)、光声光谱)、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PU生物降解速率的影响及其机理。将检验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，结果将与体外在氧化和水解条件下测定的蠕变相关联。4.测定PU表面化学成分、SME及添加剂(超氧化物歧化酶模拟物、N-乙酰半胱氨酸和修饰脱氢表雄酮)在体外静态和周期性应变条件下对单核/巨噬细胞黏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。

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.