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

• 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
• 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

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）：支持细胞附着、生长和分化的仿生基质和支架的创建是工程组织发育的关键组成部分，这里提出的实验计划旨在为实现这一目标做出贡献。天然来源的材料（例如胶原蛋白）已被广泛探索作为组织工程的支架，但伴随着显着的局限性（例如，有限的定制能力和对结构的控制）。使用促进细胞粘附的合成材料避免了与天然材料相关的许多限制，但此类材料通常需要劳动密集型的合成方案，这阻碍了它们作为组织工程支架的广泛使用。 Nylon-3 共聚物作为有前景的生物材料很有吸引力，因为这些聚合物具有模拟蛋白质主链（2-氨基酸残基），并且可以以功能多样的形式快速组装；然而，尼龙3聚合物在生物应用方面却很少受到关注。 PI 最近提出的初步结果表明，尼龙 3 共聚物对于生物材料应用具有吸引力（Lee 等人，J. Am. Chem. Soc. 131:16779 (2009)）。具体来说，一些尼龙-3 共聚物在附着到表面时，被发现比阳性对照材料支持更大的细胞粘附和铺展。最好的尼龙 3 共聚物在没有血清蛋白的情况下支持细胞附着和扩散。这里提出的研究建立在这些初步发现的基础上。我们的总体假设是，尼龙 3 共聚物的制备简便性以及该系统可实现的成分和结构变化的广度将使我们能够识别具有优异且可能独特特性的示例，作为组织工程的工具。此外，这些化学特征应该使我们能够更好地了解材料化学中离散的、受控的变化如何控制细胞行为，从而产生可用于构建具有优化成分的支架的信息。尼龙-3 体系特别适合机械分析，因为离散低聚物或特定低聚物混合物可以通过传统的固相方法制备。我们的长期目标是创造新的尼龙 3 材料，它能自发组装成三维网络（水凝胶），对细胞具有物理和化学吸引力。这种材料可以为组织工程应用提供新型支架。拟议的工作将重点关注以下目标：1) 阐明细胞粘附尼龙 3 共聚物的机制，以及 2) 生成含有直接自组装片段和控制片段的尼龙 3 嵌段共聚物细胞粘附。 公共健康相关性：支持细胞粘附和生长的材料的产生对于构建旨在替代受损或患病组织的工程环境非常重要。在本提案中，我们的目标是创造并表征新型生物材料，这些材料在结构上是合成的，但可以以仿生方式表现。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并从周围环境接收信息的方式，并将用于创建用于再生医学应用的新型 3D 支架材料。