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Cell Shape Control of Migration on Biomaterials

生物材料上迁移的细胞形状控制

基本信息

批准号：
7038349
负责人：
CHIA-CHI HO
金额：
$ 18.24万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-04-01 至 2008-03-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Tissues engineered in vitro can be used to restore and repair human tissues, potentially saving the lives of some patients waiting for organ donation. One major challenge in engineering complex tissues is directional control of cell movement. For example, different cell types assemble in specific patterns to form functional organs, capillaries sprout in the direction of new tissues or wounds, and neural cells migrate in specific directions during formation or regeneration of nervous systems. This proposed Exploratory/Development research investigates the feasibility of a completely novel approach for controlling the directional migration of cells using biodegradable scaffolds with micron-size patterns of asymmetrically shaped cell-adhesive islands. These specially shaped adhesive islands are designed to resemble combs having multiple sharp corners on one side and a smooth curved edge on the other. The basis of this design comes from previous studies with micropatterned cells, which demonstrated that single cells patterned on adhesive islands initiate lamellipodia extension - the first step of cell migration - preferentially at sharp corners of the cell periphery furthest from the cell nucleus. Cells patterned on these comb shaped islands are thus expected to extend lamellipodia preferentially from the side with multiple sharp corners. To demonstrate continuous coordination of cell migration, multiple comb-shaped islands are arranged in a circular pattern such that the sharp tips of the islands point towards the smoothly curved side of a neighboring island. The gaps between islands and between the pointed tips of the combs are set below the typical length of extended lamellipodia to allow cells to escape confinement and "hop" from one island to another in a predetermined counter-clockwise direction. A successful proof-of-principle demonstration of how cell shape, defined by the geometry of micropatterns, can be used to control the directional migration of cells on biomaterials will open many new avenues in the design of scaffolds for tissue engineering. These principles may be applied, for example, to control simultaneously the directional migration of endothelial (capillary) and hepatocyte (liver) cells into complex scaffold patterns similar to that found in liver tissues. This methodology can also be directly extended to form three-dimensional scaffolds either by cutting and twisting sheets of biomaterials or stacking multiple layers of these micropatterned sheets.

描述（由申请人提供）：体外工程组织可用于恢复和修复人体组织，可能挽救一些等待器官捐赠的患者的生命。工程复杂组织的一个主要挑战是细胞运动的方向控制。例如，不同的细胞类型以特定的模式组装以形成功能器官，毛细血管在新组织或伤口的方向上发芽，神经细胞在神经系统的形成或再生过程中以特定的方向迁移。这项拟议的探索性/开发研究调查了一种全新方法的可行性，该方法用于使用可生物降解的支架控制细胞的定向迁移，该支架具有不对称形状的细胞粘附岛的微米尺寸图案。这些特殊形状的粘合剂岛被设计成类似于在一侧上具有多个尖角并且在另一侧上具有光滑弯曲边缘的梳子。这种设计的基础来自于先前对微图案化细胞的研究，该研究表明，在粘附岛上图案化的单个细胞启动了板状伪足延伸-细胞迁移的第一步-优先在离细胞核最远的细胞周边的尖角处。因此，预期在这些梳形岛上图案化的细胞优先从具有多个尖角的一侧延伸板状伪足。为了证明细胞迁移的连续协调，多个梳状岛以圆形图案排列，使得岛的尖锐尖端指向相邻岛的平滑弯曲侧。岛之间和梳尖之间的间隙设置在延伸板状伪足的典型长度以下，以允许细胞摆脱限制并以预定的逆时针方向从一个岛“跳”到另一个岛。一个成功的原理证明的示范，细胞形状，定义的几何形状的微图案，可以用来控制细胞的定向迁移的生物材料将开辟许多新的途径，在设计支架的组织工程。这些原理可以应用于例如同时控制内皮（毛细血管）和肝细胞（肝）细胞定向迁移到类似于肝组织中发现的复杂支架模式中。这种方法也可以直接扩展到形成三维支架，通过切割和扭曲生物材料片或堆叠多层这些微图案片。