Block co-polymers combining synthetic aqnd biologically based blocks

分段聚氨酯是一种经常用于生物医学应用的“塑料”，由软段和硬段交替不相容的“块”组成。在以前由NSERC支持的工作中，我们已经生产了一系列聚氨酯，专门设计用于包含聚合物中的敏感位点，这些位点对软组织中自然发生的分子和酶的分解敏感。我们把这些位点放在聚氨酯的硬块上，这是独一无二的，因为分段聚氨酯的降解通常是通过软块来控制的。在本应用中，我们建议将注意力转向软段，并结合通过重组DNA技术产生的天然蛋白质“片段”（多肽）。具体来说，我们将使用一种基于弹性蛋白的多肽。弹性蛋白存在于动脉等弹性、可扩展的组织中，具有自发自组装成非常小的颗粒和纤维的特性。利用弹性蛋白作为软段或“塑料”，我们将能够控制聚氨酯的机械性能，降解率和生物影响。在第二部分中，我们提出通过设计和表征一系列新型弹性蛋白多肽/聚乙二醇嵌段共聚物体系来扩展弹性蛋白样多肽技术，以生产可用于各种药物输送应用的不同结构。嵌段共聚物形成不同的结构取决于亲水性（亲水）和疏水性（憎水）嵌段的比例。聚乙二醇是亲水的，而弹性肽是憎水的。有限数量的研究着眼于使用生物基共聚物系统。重组技术可用于生产具有不同结构的嵌段共聚物，其特征对药物释放应用具有重要意义。此外，这些聚合物系统可能具有生物相容性，可能对温度有潜在的反应，并且可以进行修饰以靶向药物递送到特定部位。研究生3名，博士2名，硕士1名，本科毕业论文数名。

Segmented polyurethanes, "plastics" frequently used in biomedical applications, are composed of alternating incompatible "blocks" of soft and hard segments. In work previously supported by NSERC,we have produced a family of these polyurethanes specifically designed to contain sites within the polymer that are sensitive to breakdown by molecules that occur naturally in soft tissue, enzymes. We put these sites in the hard block of the polyurethane, unique because the degradation of segmented polyurethanes is typically controlled via the soft block. In this application we propose to turn our attention to the soft segment and incorporate a naturally based protein "fragment" (polypeptide) produced via recombinant DNA technology. Specifically we will use a polypeptide based on the protein elastin. Elastin is found in elastic, extensible tissues such as arteries and has the quality of spontaneous self assembly into very small particles and fibers. In utilising the elastin as the soft segment or the "plastic", we will be able to control the mechanical properties, degradation rate and biological impact of the polyurethane. In part 2, we propose to expand the elastin-like polypeptide technology by designing and characterising a family of novel elastin polypeptide/polyethylene glycol block copolymer systems to produce different structures that can be used in a wide variety of drug delivery applications. Block copolymers form different structures depending on the proportion of hydrophilic (water loving)to hydrophobic(water hating)blocks. Polyethylene glycol is water loving and the elastin-peptide is water hating. A limited number of studies have looked at using biologically based copolymer systems. Recombinant techniques could be used to produce block copolymers that form different structures with characteristics important to in drug release applications. In addition, these polymer system would likely be biocompatible, could potentially respond to temperature and be modified to target the drug delivery to a specific site. Three graduate students, two Ph.D's and one masters as well as several undergraduate thesis students will be supported by this work.