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，组织工程构建体）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目的的哺乳动物细胞的微囊化中。现在，我们的努力是针对（1）血管化的组织工程结构，以规避菲克扩散定律的大小限制和（2）理解和控制主机响应生物材料。大部分的努力集中在模块化组织工程上，这是一种组织工程的新方法，可以产生均匀，可缩放和血管化的结构。它基于由胶原凝胶或胶原-泊洛沙胺互穿网络制成的小（目前为圆柱形）模块，包含嵌入的细胞（例如，肝细胞或胰岛）。然后用内皮细胞覆盖模块。当填充空间（例如，体内的管或组织腔）创建填充床生物反应器，其中内皮细胞使血液（以及营养物质）能够灌注。我们目前正在（i）利用这种方法的效用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心肌细胞均匀收缩片或增加移植胰岛的植入，以及（ii）理解和控制当内皮化模块植入组织腔中并受到宿主反应时发生的重塑针对与推进这一概念相关的几个挑战：例如，（a）进一步描述和验证支持模块化方法的标量的设计规则（包括Ergun方程、Thiele模量和毕奥数），以及（B）评价填充床隐含的复杂流动布置中内皮细胞的表型。NSERC的支持用于提供基本的工程基础设施，使应用或生物医学研究或作为种子资金，以开始新的项目。

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.