Vascular Assembly on Micropatterned Biomaterials

描述（由申请人提供）：体外工程组织可用于恢复和修复人体器官，可能挽救一些等待器官捐赠的患者的生命。为了在体外工程化组织，细胞被附着在可生物降解支架上的粘附蛋白网络（细胞外基质）上。在开发可行的组织中的一个主要挑战是需要控制血管的空间分布以提供足够的氧气和营养。以前在发展血管化组织方面的工作只在形成血管化皮肤方面取得了成功。尚未实现具有更复杂结构的工程血管化组织。解决这个问题的关键在于开发技术，精确组织各种细胞类型的空间排列，以模仿活组织的结构。拟议的研究是一种新的策略，诱导和空间引导内皮细胞组装成血管网络，通过控制表面形貌，空间和时间分布的细胞粘附/耐药分子，和微尺度的细胞-细胞相互作用的植入式生物材料。本研究的直接重点是建立用于创建毛细血管网络的知识和技术，这些毛细血管网络可用于未来在商业和临床相关规模上设计和制造血管化组织的努力。该研究的关键创新在于形成微尺度拓扑和化学模式，以控制细胞-细胞相互作用，并诱导内皮细胞在肝细胞旁形成功能性毛细血管网络。我们对这些微加工技术的初步研究使我们相信这些工具可以精确地定义细胞微环境和控制细胞行为。我们将使用这些工具来实现以下具体目标，这些目标共同引导我们实现在肝细胞旁创建血管网络的项目目标：1.探索使用一种新的生物可降解支架上创建毛细血管网络的方法。2.使用新的“细胞光刻”方法构建多种细胞类型，并确定微尺度内皮细胞-肝细胞相互作用对内皮细胞表型的影响。

DESCRIPTION (provided by applicant): Tissues engineered in vitro can be used to restore and repair human organs, potentially saving the lives of some patients waiting for organ donation. To engineer tissues in vitro, cells are attached to a network of adhesive proteins, the extracellular matrix, on biodegradable scaffolds. One major challenge in developing viable tissues is the need to control the spatial distribution of blood vessels to supply adequate oxygen and nutrients. Previous work in developing vascularized tissues has only been successful in forming vascularized skin. Engineering vascularized tissues that have more complex structures has not been achieved. The key to this problem lies in the development of technologies to precisely organize the spatial arrangement of various cell types to mimic the structure of living tissues. The proposed research is a venture into new strategies for inducing and spatially guiding endothelial cells to assemble into vascular networks through control of surface topography, spatial and temporal distribution of cell adhesive/resistant molecules, and microscale cell-cell interactions on implantable biomaterials. The immediate focus of this research is to establish the knowledge and technology for creating capillary networks that can be used for future effort for designing and fabricating vascularized tissues at a commercially and clinically relevant scale. The key innovation of this research lies in the formation of microscale topological and chemical patterns to control cell-cell interactions and induce endothelial cells to form functional capillary networks next to liver cells. Our preliminary investigations with these microfabrication techniques have convinced us of the utility of these tools for precisely defining cellular microenvironments and controlling cell behaviors. We will use these tools to achieve the following specific objectives that altogether lead us towards our project goal of creating vascular networks next to liver cells: 1. Explore the use of a novel polyelectrolyte patterning method for creating a network of capillaries on biodegradable scaffolds. 2. Structure multiple cell types using a novel "Cell Photolithography" method and ascertain the effects of microscale endothelium-hepatocyte interactions on the endothelial phenotype.