Design and study of materials and bioreactor culture process to fabricate a vascularized bioartificial pancreas device

2000年，世界卫生组织估计，超过1.77亿人患有糖尿病，其中包括200多万加拿大人。糖尿病及其并发症给加拿大医疗系统造成的财政负担是巨大的，估计每年高达132亿美元。治疗I型糖尿病的一大挑战是预防晚期并发症，这通常是通过强化胰岛素治疗来实现的。血管生物人工胰腺的组织工程可能成为治疗糖尿病的重要因素。然而，深埋在工程化组织结构中的细胞的存活因缺乏毛细血管发育而受到影响，导致坏死。由于这一限制，人们对大组织块的培养和生长知之甚少。组织工程学整合了化学和生物技术工程、生物材料、细胞生物学和移植等科学，以创造组织和器官替代品。组织工程产品的开发面临着几个挑战：细胞来源、免疫兼容性、生长过程中无菌和一致性的保持、制造过程的可扩展性等。需要一个培养过程来控制细胞和组织的生长。总体目标是开发和使用共培养过程来指导血运生物人工胰腺在定义的3-D环境中的生长。这里提出的主要概念包括使用生物活性支架和生物反应器系统，其中可以调节操作条件来引导胰腺组织和微血管的形成。因此，这一建议中描述的方法在Vermette的实验室中得到了很好的确立，并得到了初步结果的支持。将创建有影响力的出版物和知识产权(IP)。该项目将为培养高素质的生物技术工程人才做出重大贡献。

In 2000, the World Health Organization estimated that over 177 millions people have diabetes, including more than 2 millions Canadians. The financial burden of diabetes and its complications on the Canadian healthcare system is enormous estimated at $13.2 billion every year. A major challenge in the treatment of Type I diabetes is the prevention of late complications, usually achieved by intensified insulin treatment.   Tissue engineering of a vascularised bioartificial pancreas could become an important element in the treatment of diabetes. However, survival of cells deeply embedded in engineered tissue constructs is compromised by lack of capillary development causing necrosis. Because of this limitation, culture and growth of large tissue mass are poorly understood.   Tissue engineering integrates the sciences of chemical and biotechnological engineering, biomaterials, cell biology, and transplantation to create tissue and organ substitutes. Several challenges face the development of an engineered tissue product: cell sourcing, immuno-compatibility, maintenance of sterility and uniformity during the growth process, "scalability" of the manufacturing process, etc. There is a need for a culture process to control cell and tissue growth.   The general objective is to develop and use a co-culture process to guide the growth of a vascularized bioartificial pancreas within a defined 3-D environment. The main concept proposed here consiststo use bioactive scaffolds and a bioreactor system in which operating conditions can be modulated to guide pancreatic tissue and micro-vessel formation.   The methods described in this proposal are well established in Vermette's laboratory and are supported by preliminary results. High-impact publications and intellectual property (IP) will be created. This project will make a major contribution to the training of highly qualified personnel in biotechnological engineering.