Vascular Assembly on Micropatterned Biomaterials

微图案生物材料上的血管组装

• 批准号: 7095368
• 负责人: CHIA-CHI HO
• 金额: $ 18.61万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-15 至 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7095368
• 关键词: biodegradable product; bioengineering /biomedical engineering; biomaterial development /preparation; biomimetics; biotechnology; blood vessel prosthesis; capillary bed; cell adhesion; cell cell interaction; cell line; electrolytes; liver cells; medical implant science; molecular assembly /self assembly; tissue engineering; vascular endothelium

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.

描述（由申请人提供）：在体外设计的组织可用于恢复和修复人体器官，有可能挽救一些等待器官捐赠的患者的生命。在体外工程组织中，细胞附着在可生物降解支架上的粘合蛋白网络，细胞外基质。开发可行组织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养分。先前在开发血管组织的工作仅在形成血管化皮肤方面才成功。尚未实现具有更复杂结构的工程血管化组织。这个问题的关键在于技术的发展，以精确组织各种细胞类型的空间排列以模仿生物组织的结构。拟议的研究是通过控制表面形貌，细胞粘合剂/抗性分子的空间和时间分布以及在可植入的生物材料上的微观细胞 - 细胞相互作用来诱导和空间引导内皮细胞组装成血管网络的新策略。这项研究的直接重点是建立用于创建毛细管网络的知识和技术，这些毛细血管网络可用于以商业和临床相关的规模设计和制造血管化组织的未来努力。这项研究的关键创新在于形成微观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形成肝细胞旁边的功能毛细血管网络。我们对这些微观加工技术的初步研究使我们相信了这些工具的实用性，以精确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特定目标，这些目标完全使我们朝着在肝细胞旁边创建血管网络的项目目标：1。探索使用新颖的聚电解质图案方法，以在可生物降解的可生物降解架上创建毛细血管网络。 2。使用新型的“细胞光刻”方法结构多种细胞类型，并确定微观内皮细胞相互作用对内皮表型的影响。