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

塑料在人体内降解成无害的产品，在生物医学工程中得到越来越多的应用。这些应用包括组织替换或修复、药物输送和外科缝合。组织工程涉及聚合物支架的构建。这些海绵基本上都是海绵，可以与所需组织的细胞一起种植，然后植入人体内，以取代受损的组织。理想情况下，塑料应该是生物相容的(即不会产生炎症)，具有与其所取代的组织相似的机械性能，允许组织细胞快速增殖，并以允许细胞生长的速度降解。人们认为，某些中链长度的聚-3-羟基烷酸酯(MCL-PHAs)可以进行化学修饰，以满足所有这些苛刻的要求。如果适当控制生长条件，这些弹性塑料可以在某些细菌内大量生产。此外，它们还可能满足目前尚未解决的组织支架的另一项要求。异物植入人体内可能引发凝血或导致微生物感染。如果塑料能够缓慢释放抗凝血因子和抗生素，这些问题就可以得到很好的缓解。该项目建议开发一种在生物反应器中高效生产合适的MCL-PHA的方法。它将被处理，使其在人体内可降解(以受控的速度)，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在支架上定植的材料。

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.