Biomaterials and Processes for Tissue Engineering

生物材料和基于这些材料的设备（例如，组织工程结构）产生生物反应，并且由生物材料（或移植细胞）介导的对该反应的控制决定了设备的成功实施。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尺寸限制。在某种程度上，我们的努力集中在模块化组织工程上，这是一种新颖的方法，可以产生统一的、可扩展的和血管化的结构。它基于通常由胶原凝胶制成的小（~400微米）模块，该模块含有嵌入的细胞（例如肝细胞或胰岛），这些细胞被内皮细胞覆盖，以实现血液和营养物质的灌注。在目标1中，我们将准备包含和显示指导性线索的模块组件（使用基于脱细胞基质的水凝胶），以增强血管化以及控制细胞行为。我们还将使用微流体制造更小的模块，使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，将推进含有共聚物的甲基丙烯酸（MAA）（45%的MAA，其余的甲基丙烯酸甲酯），诱导新血管的形成。值得注意的是，这在没有额外生长因子或细胞的情况下发生。在目标2中，我们将合成新的MAA共聚物，用于涂料或注射凝胶。

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.