Tissue engineering

我的研究项目的基本主题是生物材料和基于这些材料的设备（例如，组织工程结构）是生物反应的激动剂。多年来，这一主题主要表现在心血管生物材料的血液相容性问题和用于细胞移植的哺乳动物细胞的微胶囊化。现在我们的工作方向是：(1)组织工程构建的血管化，以绕过菲克扩散定律施加的尺寸限制；(2)理解和控制宿主对生物材料的反应。大部分的努力都集中在模块化组织工程上，这是一种新颖的组织工程方法，可以产生统一的、可扩展的和血管化的结构。它基于由胶原凝胶或胶原-poloxamine互穿网络制成的小型（目前为圆柱形）模块，包含嵌入细胞（例如肝细胞或胰岛）。然后用内皮细胞覆盖这些模块。当填充一个空间（例如，体内的管道或组织腔）时，会产生一个填充床生物反应器，其中内皮细胞使血液（以及营养物质）得以灌注。我们目前正在(i)利用这种方法的实用价值来创建用于癌症后重建的脂肪组织或用于治疗心力衰竭的均匀收缩的心肌细胞片或增加移植胰岛的植入；（ii）理解和控制当内皮化模块植入组织腔并受到宿主反应时发生的重塑与推进这一概念相关：例如，(a)进一步描述和验证支撑模块化方法可扩展性的设计规则（涉及Ergun方程；Thiele模量和Biot数），以及(b)在复杂的流动安排中评估内皮细胞的表型隐含在填充床中。NSERC的支持用于提供基础工程基础设施，以使应用或生物医学研究或作为启动新项目的种子资金。

The underlying theme of my research program is that biomaterials and the devices based on these materials (e.g., tissue-engineered constructs) are agonists of a biological response. Over the years this theme has manifested itself primarily in the problem of blood compatibility of cardiovascular biomaterials and in the microencapsulation of mammalian cells for the purpose of cell transplantation. Now our efforts are directed towards (1) vascularisation of tissue engineering constructs to circumvent the size limits imposed by Fick's law of diffusion and (2) understanding and controlling the host response to biomaterials. Much of the effort is centered on modular tissue engineering, a novel approach to tissue engineering that results in uniform, scaleable and vascularised constructs. It is based on small (currently cylindrical) modules made from collagen gel or a collagen-poloxamine interpenetrating network, containing embedded cells (e.g., liver cells or pancreatic islets). The modules are then covered with endothelial cells. When filling a space (e.g., a tube or a tissue cavity, in vivo) a packed bed bioreactor is created, in which the endothelial cells enable blood (and hence nutrients) to be perfused. We are currently (i) exploiting the utility of this approach to create fat tissue for post-cancer reconstruction or uniformly contracting sheets of heart muscle cells for the treatment of heart failure or to augment the engraftment of transplanted pancreatic islets and (ii) understanding and controlling the remodelling that occurs when endothelialized modules are implanted in a tissue cavity and subject to the host response The proposed efforts are directed to several of the challenges associated with advancing this concept: for example, (a) further delineation and validation of the design rules (involving Ergun equation; Thiele modulus and Biot number) that underpin the scaleability of the modular approach and (b) evaluation of the phenotype of the endothelial cells in the complex flow arrangements implicit to a packed bed. NSERC support is used to provide the fundamental engineering infrastructure to enable the applied or biomedical studies or as seed money to begin new projects.