Biomaterials and Processes for Tissue Engineering

生物材料和基于这些材料的装置(例如，组织工程构建物)产生生物反应，正是对该反应的控制，由生物材料(或移植细胞)介导，决定了装置的成功实施。我们目前的努力是针对组织工程结构的血管化，以绕过菲克扩散定律施加的大小限制。在某种程度上，我们的努力集中在模块化组织工程上，这是一种新的方法，可以产生统一、可伸缩和血管化的结构。它基于通常由含有嵌入细胞(例如肝细胞或胰岛)的胶原凝胶制成的小型(~400微米)模块，这些细胞被内皮细胞覆盖，以实现血液和营养灌流。在目标1中，我们将准备结合并显示指示信号的模块组件(使用脱细胞基质水凝胶)以增强血管形成以及控制细胞行为。我们还将使用微流体生产更小的模块，以在新形成的血管和移植细胞之间产生更紧密的接触。在第二个领域，将推进一种含有甲基丙烯酸(MAA)的共聚物(45%MAA，剩余的甲基丙烯酸甲酯)，它可以诱导新血管的形成。值得注意的是，这在没有额外的生长因子或细胞的情况下发生。在目标2中，我们将合成新型MAA共聚物，用作涂料或可注射凝胶。**NSERC的支持用于提供基本的工程基础设施，以实现应用或生物医学研究；生物医学研究属于其他机构的任务范围。**加拿大正在迅速老龄化，导致对将提高生产率并降低发病率和死亡率的技术的需求大幅增加。通过提供生长替代组织的手段，组织工程学提出将疾病管理从治疗衰竭器官的症状转变为功能修复。******

Biomaterials and the devices based on these materials (e.g., tissue-engineered constructs) generate a biological response and it is control of that response, mediated by the biomaterial (or the transplanted cells) that dictate the successful implementation of the device. Our current efforts are directed towards vascularization of tissue engineering constructs to circumvent the size limits imposed by Fick's law of diffusion. In part, our effort is centered on modular tissue engineering, a novel approach that results in uniform, scaleable and vascularised constructs. It is based on small (~400 µm) modules made typically from collagen gel containing embedded cells (e.g., liver cells or pancreatic islets) which are covered with endothelial cells to enable blood and nutrient perfusion. In aim 1, we will prepare module components that incorporate and display instructive cues (using decellularized matrix based hydrogels) to enhance vascularization as well as control cell behavior. We will also produce smaller modules using microfluidics to produce more intimate contact between the newly formed vessels and the transplanted cells. In a second area, will advance a methacrylic acid (MAA) containing copolymer (45% MAA, remainder methyl methacrylate) that induces the formation of new blood vessels. Remarkably, this occurs without additional growth factors or cells. In aim 2, we will synthesize novel MAA copolymers, to be used as coatings or as an injectable gel. **NSERC support is used to provide the fundamental engineering infrastructure to enable the applied or biomedical studies; the biomedical studies fall within the mandate of other agencies.**Canada is aging rapidly, leading to a substantial increase in the demand for technologies that will improve productivity and decrease morbidity and mortality. By providing the means to grow replacement tissues, tissue engineering proposes to shift disease management from treatment of symptoms of a failing organ to functional repair. ******