LONG TERM BIODEGRADATION OF ELASTOMERIC BIOMATERIALS

拟议的研究计划是目前研究的延伸 旨在从根本上理解生物相容性， 生物医学弹性体的生物稳定性，特别是聚氨酯。 的 总体目标是检验所提出的假设， 生物降解植入聚（醚）（PEU），其中涉及 细胞/聚合物反馈机制。 蛋白质的初始吸附 影响随后的细胞粘附和活化。 后者可能 随后是呼吸爆发，其产生氧物质， 最有可能导致聚合物链的氧化降解。 改变的表面性质和降解产物可进一步 影响蛋白质吸附和/或细胞粘附的过程， 通过反馈机制激活。 与此同时， 溶酶体酶和其他介质可能导致其他细胞变得 激活 为了证实和/或修改假设， 建立运行机制，开展试点工作 已知组成的PEU，有和没有特定的添加剂， 增强生物稳定性。 实验程序建议：1） 测定人血浆蛋白对候选PEU的吸附 使用放射免疫测定（RIA）或免疫金蛋白A标记， 扫描电子显微镜（SEM）; 2）定量测量细胞 使用椎间融合器植入系统进行粘附和活化; 3）表征 使用光学显微镜（OM）观察植入PEU的表面“腐蚀”， SEM，通过提取物的ATR-FTIR和GPC分析确定化学变化， 并确定对性能特性的影响，包括疲劳 4）评估单核细胞呼吸爆发介导的PEU降解 在体外用单核细胞/巨噬细胞培养系统;和5）建立 PEU在体外使用金属氧化降解的化学， 催化过氧化物处理和加速条件。

The proposed research program is an extension of current studies directed toward a fundamental understanding of biocompatibility and biostability of biomedical elastomers, specifically polyurethanes. The overall objective is to test the proposed hypothesis for the biodegradation of implanted poly(etherurethanes) (PEUs) which involves cell/polymer feedback mechanism. The Initial adsorption of proteins affects the subsequent cellular adhesion and activation. The latter may be followed by a respiratory burst which produces oxygen species that are most likely responsible for oxidative degradation of the polymer chain. The altered surface properties and degradation products may further affect the process of protein adsorption and/or cell adhesion and activation via feedback mechanisms. Simultaneously, the exocytosis of lysosomal enzymes and other mediators may cause other cells to become activated. In order to confirm and/or modify the hypothesis and to establish operative mechanisms, experimental procedures will be carried out on PEUs of known composition, with and without specific additives to enhance biostability. Experimental procedures are proposed to: 1) Determine the adsorption of human blood plasma proteins to candidate PEUs using radioimmunoassay (RIA) or immunogold protein A labelling with scanning electron microscopy (SEM); 2) Quantitatively measure cell adhesion and activation using the cage implant system; 3) Characterize surface 'corrosion' of implanted PEUs using optical microscopy (OM) and SEM, identify chemical changes by ATR-FTIR and GPC analysis of extracts, and determine the effects on performance properties including fatigue resistance; 4) Assess monocyte respiratory burst mediated PEU degradation in vitro with the monocyte/macrophage culture system; and 5) Establish the chemistry of oxidative degradation of PEUs in vitro using metal- catalyzed peroxide treatment and accelerated conditions.