Using Block Copolymers to Control Cell Behavior

描述(由申请人提供)：本提案的目标是培养首席研究员成为组织工程领域的独立科学家。该提案的头两年将涉及细胞生物学和生物科学领域的教学培训。接下来的三年将包括执行一个由导师指导的研究项目。该项目包括研究使用嵌段共聚物控制成骨前细胞系的细胞反应。使用活性自由基聚合或可控自由基聚合，可以很容易地从丙烯酸酯和甲基丙烯酸酯系列单体中合成定义良好的嵌段共聚物。众所周知，这些单体可以产生生物相容的聚合物，并在生物材料中得到广泛应用。由相分离的嵌段共聚物得到的形态可以通过嵌段的大小和空间排列来控制。预计这些形态可以控制细胞系的行为。在大多数聚合物体系中，控制细胞反应的要么是形态，要么是表面化学。在所提出的系统中，形态和表面化学都将以受控的方式改变，并且可以确定它们对给定细胞响应的影响。这将导致对细胞-材料相互作用的更好理解，以及改进的组织工程支架的设计。纤维连接蛋白分析将被用来测量聚合物表面的粘附性和构象。吸附在聚合物表面的蛋白质在调节细胞的行为和表型方面起着很大的作用。黏附和构象数据有望与MC3T3-E1细胞系的细胞反应相关联。作为该提案的一部分，将测量几种细胞反应，包括细胞增殖和活性、细胞形态和黏附以及细胞分化。了解系统调制的聚合物表面与细胞系的相互作用将导致改进支架材料的发展。

DESCRIPTION (provided by applicant): The goal of this proposal is to train the principle investigator to become an independent scientist in the field of tissue engineering. The first two years of the proposal will involve didactic training in the area of cell biology and the biological sciences. The next three years will involve executing a mentor guided research project. This project involves studying controlling the cellular response of a pre-osteoblast cell line using block copolymers. Using living or controlled free radical polymerization well-defined block copolymers from the acrylate and methacrylate families of monomer can be readily synthesized. These monomers are known to yield polymers that are biocompatible and used widely in biomaterials. The resulting morphologies from the phase segregated block copolymers can be controlled by the block size and spatial arrangement. It is expected that these morphologies can control the behavior of the cell lines. In most polymer systems, either the morphology or the surface chemistry is varied to control cell response. In the proposed system, both the morphology and surface chemistry will be varied in a controlled fashion and the effect of each on a given cellular response can be determined. This will lead to a better understanding of cell-material interaction and to the design of improved tissue engineering scaffolds. Fibronectin assays will be employed to measure the adhesion and conformation on the polymer surface. Proteins adsorbed to a polymer surface play a large role in regulating the behavior and phenotype of the cell. The adhesion and conformation data is expected to correlate to the cell responses of a MC3T3-E1cell line. Several cell responses will be measured as part of this proposal, cell proliferation and activity, cell morphology and adhesion and cell differentiation. Understanding the interaction of a systematically modulated polymer surface with a cell line will lead to the development of improved scaffold materials.