Development of mcl-PHA as a bioactive scaffold for tissue engineering

在人体内降解成无害产品的塑料在生物医学工程中的应用越来越广泛。这些应用包括组织替换或修复、药物输送和手术缝合。组织工程涉及聚合物支架的构建。这些本质上是海绵，可以用所需组织的细胞播种，并植入人体以取代受损的组织。理想情况下，塑料应该具有生物相容性（即不会产生炎症），与被替换的组织具有相似的机械性能，允许组织细胞快速增殖，并以允许细胞生长的速度降解。人们相信，某些中链长聚3-羟基烷酸酯（mcl- pha）可以通过化学修饰来满足所有这些要求。如果生长条件得到适当控制，这些弹性体塑料在某些细菌体内大量生产。此外，它们可能能够满足目前尚未解决的组织支架的另一种要求。将异物植入人体可能引发凝血或导致微生物感染。如果塑料可以缓慢释放抗凝血因子和抗生素，这些问题就可以得到缓解。本项目建议开发一种在生物反应器中有效生产合适的mcl-PHA的方法。将对其进行加工，使其在人体内可降解（以可控的速率），并能够接受抗生素和抗凝血因子的附着，以及允许组织细胞更快地定植支架的材料。

Plastics that degrade into harmless products in the human body are finding increasing applications in biomedical engineering. These applications include tissue replacement or repair, drug delivery and surgical sutures. Tissue engineering involves the construction of polymer scaffolds. These are essentially sponges that can be seeded throughout with cells of the desired tissue and implanted in the human body to replace damaged tissue. Ideally the plastic should be biocompatible (i.e. does not generate inflammation), have similar mechanical properties to the tissue that it is replacing, allow the tissue cells to proliferate rapidly, and degrade at a rate that allows the cells room to grow. It is believed that certain medium-chain-length poly-3-hydroxyalkanoates (mcl-PHAs) can be chemically modified to fulfill all of these demanding requirements. These elastomeric plastics are produced in large qualities inside certain bacteria if the growth conditions are properly controlled. In addition they may be able to satisfy another requirement of tissue scaffolds that is not currently being addressed. Implantation of foreign objects into the human body may trigger clotting or lead to microbial infection. These problems can be  alleviated if the plastic can slowly release anti-clotting factors and antibiotics. This project proposes to develop a methodology for the efficient production of suitable mcl-PHA in a bioreactor. It will be processed to render it degradable (at a controlled rate) in the human body and able to accept the attachment of antibiotics and anti-clotting factors, as well as materials that allow the more rapid colonization of the scaffold by tissue cells.