Novel Biodegradable Electrically Conducting Polymers for Nerve Regeneration

9702882施密特拟议的研究重点是合成一种新型的生物可降解聚合物，这种聚合物将具有固有的导电性。这项研究是由过去的工作推动的，这些工作表明电场和电荷可以促进几种组织的愈合，包括骨骼和神经。目前可用的方法存在缺陷。外部电磁场无法准确地将电效应定位到所需的组织，使用不可生物降解的导电或带电材料可能会带来与任何永久性材料相关的长期风险。因此，有充分的动机开发一种可生物降解的聚合物，这种聚合物具有理想的导电性能，可以定位于所选的组织，并且不会构成长期的健康风险。目前还不存在这样的聚合物。除了可能用于周围神经再生外，这种聚合物还可以应用于组织工程的其他领域，如脊髓再生和肌肉组织。为了合成可生物降解的导电聚合物，导电吡咯齐聚物将通过可水解(可降解)的氨基甲酸酯键相互偶联。选择吡咯是基于PI之前广泛的研究表明，聚吡咯具有生物相容性，可以显著地用于S神经细胞的轴突延伸。PI也表明，以引导通道形式存在的聚(吡咯)比硅胶等惰性材料更能引导周围神经再生。不幸的是，目前形式的聚(吡咯)不能生物降解，也不容易加工成不同的形状。因此，吡咯低聚物将与氨基甲酸酯连接起来，使其可生物降解，更容易加工。选择氨基甲酸酯键的原因有很多，包括氨基甲酸酯先前在心脏瓣膜等临床应用中的应用，以及未交联型的氨基甲酸乙酯是可生物降解和柔韧的。在聚合物产品被证明对活组织有害的不太可能的情况下，将使用其他交联剂(例如，酯键)。综上所述，这些研究将集中在合成一种新型的可生物降解的导电聚合物，基于先前的工作，表明电荷有利于伤口愈合，特别是有利于神经再生。因此，合成的聚合物不仅将是一种有用的材料，不仅可以用于辅助周围神经再生的设备(例如神经引导通道)，而且还可以用于其他组织工程应用。***

9702882 Schmidt The proposed research focuses on the synthesis of a novel biodegradable polymer that will be inherently electrically conductive. This research is motivated by past work which demonstrates that electric fields and electrical charges improve the healing of several tissues, including bone and nerve. There are drawbacks to the presently available approaches. External electromagnetic fields suffer from the inability to accurately localize the electrical effect to the desired tissue, and the use of non-biodegradable electrically-conducting or electrically - charged materials can pose long-term risks that are associated with any permanent material. Thus, there is ample motivation to develop a biodegradable polymer, which has desirable electrically conductive properties that can be localized to the tissue of choice, and which will not pose long-term health risks. Such a polymer does not currently exist. In addition to its possible utility for peripheral nerve regeneration, the polymer could also be applied to other areas of tissue engineering as well, such as spinal cord regeneration and muscle tissue. To synthesize a biodegradable electrically conducting polymer, electrically conducting pyrrole oligomers will be coupled to one another via hydrolyzable (degradable) urethane linkages. Pyrrole was selected based on extensive previous research by the PI showing that poly(pyrrole) is biocompatible and can be used to significantly s the extension of axons from nerve cells. Poly(pyrrole), in the form of guidance channels, has also been shown by the PI to guide peripheral nerve regeneration better than inert materials such as silicone. Unfortunately, poly(pyrrole) in its present form is not biodegradable and not easily processed into different shapes. Thus, pyrrole oligomers will be coupled with urethane linkages to render it biodegradable an d more easily processed. The urethane linkage was selected for many reasons, including urethane's prior use in clinical applications such as heart valves and the fact that urethane, in its uncrosslinked form, is biodegradable and pliable. Other cross linking chemistries (e.g., an ester linkage) will be utilized in the unlikely event that the polymer product proves to be deleterious to living tissue. In summary, the proposed studies will focus on the synthesis of a novel biodegradable electrically conducting polymer, based on previous work showing that electrical charges are beneficial to wound healing, and in particular, to nerve regeneration. Thus, the resultant polymer will be a useful material not only for devices to aid peripheral nerve regeneration (e.g., nerve guidance channels), but for other tissue engineering applications as well. ***