Nylon-3 Copolymers as Synthetic Cell-Adhesive Moieties for Tissue Engineering

Nylon-3 共聚物作为组织工程的合成细胞粘附部分

基本信息

批准号：
8090829
负责人：
SAMUEL H. GELLMAN
金额：
$ 20.88万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-01 至 2013-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8090829
关键词：
3-Dimensional Achievement Adhesions Adhesives Adsorption Amino Acids Architecture Attention Biocompatible Materials Biological Biomimetics Cell Adhesion Cell Adhesion Molecules Cell Density Cell Surface Proteins Cell surface Cell-Cell Adhesion Cell-Matrix Junction Cells Cellular Morphology Characteristics Chemicals Chemistry Collagen Development Differentiation and Growth Engineering Environment Environment Design Family Fibroblasts Fibronectins Generations Glass Goals Hydrogels Individual Investigation Lactams Laminin Least-Squares Analysis Libraries Methods Modeling Nylons Phase Polymers Polystyrenes Preparation Property Proteins Protocols documentation Regenerative Medicine Research Screening procedure Serum Serum Proteins Signal Transduction Solid Structure Supporting Cell Surface System Testing Time Tissue Engineering Tissues Variant Vertebral column Vitronectin Work base biomaterial development cell behavior cell growth copolymer design mimetics polymerization programs prospective protein expression scaffold self assembly tissue culture tool trend

3-Dimensional Achievement Adhesions Adhesives Adsorption Amino Acids Architecture Attention Biocompatible Materials Biological Biomimetics Cell Adhesion Cell Adhesion Molecules Cell Density Cell Surface Proteins Cell surface Cell-Cell Adhesion Cell-Matrix Junction Cells Cellular Morphology Characteristics Chemicals Chemistry Collagen Development Differentiation and Growth Engineering Environment Environment Design Family Fibroblasts Fibronectins Generations Glass Goals Hydrogels Individual Investigation Lactams Laminin Least-Squares Analysis Libraries Methods Modeling Nylons Phase Polymers Polystyrenes Preparation Property Proteins Protocols documentation Regenerative Medicine Research Screening procedure Serum Serum Proteins Signal Transduction Solid Structure Supporting Cell Surface System Testing Time Tissue Engineering Tissues Variant Vertebral column Vitronectin Work base biomaterial development cell behavior cell growth copolymer design mimetics polymerization programs prospective protein expression scaffold self assembly tissue culture tool trend

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项目摘要

DESCRIPTION (provided by applicant): The creation of biomimetic substrates and scaffolds that support cell attachment, growth, and differentiation is a crucial component in the development of engineered tissues, and the experimental program proposed here aims to contribute to the achievement of this goal. Naturally-derived materials (e.g., collagen) have been widely explored as scaffolds for tissue engineering, but are accompanied by significant limitations (e.g., limited tailor ability and control over architecture). The use of synthetic materials that encourage cell adhesion avoids many of the limitations associated with natural materials, but such materials often require labor-intensive synthetic protocols, which hinders their widespread use as tissue engineering scaffolds. Nylon-3 copolymers are intriguing as prospective biomaterials because these polymers have a protein-mimetic backbone (2-amino acid residues) and can be assembled rapidly in functionally diverse forms; however, nylon-3 polymers have received very little attention in terms of biological applications. The PIs have recently presented preliminary results showing that nylon-3 copolymers are attractive for biomaterials applications (Lee et al., J. Am. Chem. Soc. 131:16779 (2009)). Specifically, some nylon-3 copolymers, when attached to a surface, were found to support greater cell adhesion and spreading than did positive control materials. The best of the nylon-3 copolymers supported cell attachment and spreading in the absence of serum proteins. The research proposed here builds on these initial discoveries. Our general hypothesis is that the ease with which nylon-3 copolymers can be prepared and the breadth of compositional and architectural variation that can be achieved with this system will enable us to identify examples with excellent and possibly unique characteristics as tools for tissue engineering. Moreover, these chemical features should allow us to gain a better understanding of how discrete, controlled changes in materials chemistry can control cell behavior, thereby yielding information that can be used to construct scaffolds with an optimized composition. The nylon-3 system is particularly amenable to mechanistic analysis because discrete oligomers or defined oligomer mixtures can be prepared via conventional solid-phase methods. Our long-range goal is to create new nylon-3 materials that spontaneously assemble into three- dimensional networks (hydrogels) that are physically and chemically attractive to cells. Such materials could provide new types of scaffolds for tissue engineering applications. The proposed work will focus upon the aims of: 1) Elucidating the mechanism(s) by which cells adhere to nylon-3 copolymers, and 2) Generating nylon-3 block copolymers containing segments that direct self-assembly as well as segments that control cell adhesion. PUBLIC HEALTH RELEVANCE: The generation of materials that support cell adhesion and growth is important in the construction of engineered environments that are designed to replace damaged or diseased tissues. In this proposal, we aim to create and characterize new types of biomaterials that are synthetic in structure, but that can behave in a biomimetic manner. These biomaterials will allow us to better understand the manner in which cells interact with and receive information from their surroundings, and will be used to create a new type of 3-D scaffold material for use in regenerative medicine applications.

描述（由申请人提供）：建立支持细胞附着，生长和分化的仿生底物和脚手架是工程组织开发的关键组成部分，此处提出的实验计划旨在为实现这一目标做出贡献。自然衍生的材料（例如，胶原蛋白）已被广泛探索为组织工程的脚手架，但伴随着重大限制（例如，裁缝能力有限，对建筑的控制能力有限）。促进细胞粘附的合成材料的使用避免了与天然材料相关的许多局限性，但是这种材料通常需要劳动密集型的合成方案，这阻碍了它们广泛用作组织工程脚手架。尼龙-3共聚物作为前瞻性生物材料而引人入胜，因为这些聚合物具有蛋白质模拟主链（2-氨基酸残基），并且可以以功能多样的形式迅速组装。但是，尼龙-3聚合物在生物应用方面几乎没有得到关注。 PI最近提出了初步结果，表明Nylon-3共聚物对生物材料的应用有吸引力（Lee等，J。Am。Chem。Soc。131：16779（2009））。具体而言，与阳性对照材料相比，发现某些尼龙-3共聚物在表面附着时支持更大的细胞粘附和扩散。尼龙-3共聚物中最好的在没有血清蛋白的情况下支持细胞的附着和扩散。这里提出的研究基于这些最初的发现。我们的总体假设是，可以制定尼龙-3共聚物的易度性以及该系统可以实现的组成和建筑变化的广度将使我们能够鉴定出具有出色且可能具有独特特征作为组织工程工具的示例。此外，这些化学特征应该使我们能够更好地了解材料化学的离散，受控变化如何控制细胞行为，从而产生可用于用优化组成构建支架的信息。 Nylon-3系统特别适合机械分析，因为可以通过常规的固相方法制备离散的低聚物或定义的低聚物混合物。我们的远程目标是创建新的Nylon-3材料，这些材料自发地组装成三维网络（水凝胶），它们在物理上和化学上对细胞具有吸引力。这样的材料可以为组织工程应用提供新型的脚手架。拟议的工作将集中于以下目的：1）阐明细胞粘附在尼龙-3共聚物上的机制，以及2）生成尼龙-3块共聚物，这些尼龙-3块共聚物含有直接自组装以及控制细胞粘附的片段。公共卫生相关性：支持细胞粘附和生长的材料的产生在旨在替代受损或患病组织的工程环境的建设中很重要。在此提案中，我们旨在创建和表征结构合成的新型生物材料类型，但可以以仿生的方式行事。这些生物材料将使我们能够更好地了解细胞与周围环境相互作用和接收信息的方式，并将用于创建一种新型的3-D支架材料，以用于再生医学应用。