Non-Covalent Modification of Collagen Scaffolds

胶原蛋白支架的非共价修饰

• 批准号: 6957114
• 负责人: Michael S Yu
• 金额: $ 21万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6957114
• 关键词: biomimetics; chemical conjugate; collagen; intermolecular interaction; polyethylene glycols; protein binding; protein structure function; tissue engineering; tissue support frame

DESCRIPTION (provided by applicant): Collagen is used in a variety of medical applications ranging from hemostatic materials and biocompatible coatings to drug delivery and tissue engineering. Traditionally, collagen is used as passive (but biocompatible) materials that protect injured sites and support healing processes. Today, there is a renewed interest in collagen as bioactive scaffolds that can provide ideal environment for specific tissue formation. This has led to widespread interests in immobilizing bioactive components (such as growth factors, antimicrobial agents, or cell-repellent) to natural collagen. In this proposal we wish to investigate nonchemical immobilization of collagen mimetic peptides (CMP) and CMP derivatives on collagen scaffolds, and explore its potential as a new collagen modification technique targeted for microvasculature engineering. Collagen mimetic peptides (CMPs) are peptides, typically of less than 30 amino acids, composed of multimers of known helicogenic trimers (e.g. ProHypGly). They have been highly useful in determining the structure and stability of natural collagens and their collagen-like triple helical structure and reversible association (melting) behaviors are documented in the literatures. In our previous studies, we discovered that CMPs can bind to collagen films (type I) under controlled thermal condition. Main goals of this research are to further understand the CMP-collagen interaction, identify optimal CMP structure that exhibit efficient and reversible binding to collagen under physiological or near-physiological condition, and demonstrate the practical use of the poly(ethyleneglycol)-CMP conjugate in controlling the endothelial cell (ED) organization in 2D and 3D collagen scaffolds. In the long run, we wish to develop this approach into a more general collagen modification method that can provide novel solutions to complications after vascular and ocular surgery and to add therapeutic activity to conventional collagen-based biomaterials (see support letter from The Wilmer Ophthalmological Institute of the Johns Hopkins Medical School).

描述（由申请人提供）：胶原蛋白用于从止血材料和生物相容性涂料到药物输送和组织工程的各种医疗应用中。传统上，胶原蛋白被用作保护受伤部位并支持愈合过程的被动（但生物相容性）材料。如今，人们对胶原蛋白作为生物活性支架有了新的兴趣，可以为特定组织形成提供理想的环境。这导致对固定生物活性成分（例如生长因子，抗菌剂或细胞固定物）的普遍兴趣。在该提案中，我们希望研究胶原蛋白支架上的胶原蛋白模拟肽（CMP）和CMP衍生物的非化学固定化，并探索其作为针对微堡工程的新胶原修饰技术的潜力。 胶原蛋白模拟肽（CMP）是肽，通常小于30个氨基酸，由已知的旋转三聚体的多聚体组成（例如，proHypgly）。它们在确定天然胶原蛋白的结构和稳定性及其类似胶原蛋白的三重螺旋结构和可逆关联（熔化）行为方面非常有用。在以前的研究中，我们发现CMP可以在受控的热条件下与胶原蛋白膜（I型）结合。 这项研究的主要目标是进一步了解CMP-Collagen的相互作用，确定在生理或近乎生理条件下与胶原蛋白表现出高效且可逆的结合的最佳CMP结构，并证明了聚（乙二醇）-CMP结合物-CMP结合物在控制内皮细胞（ED）（ED）中的2D和3D collag collag collag。从长远来看，我们希望将这种方法开发为一种更一般的胶原蛋白修饰方法，该方法可以为血管和眼部手术后的并发症提供新颖的解决方案，并为基于常规的胶原蛋白生物材料的治疗活性增加（请参阅Johns Hopkins Hopkins Hopkkins医学院的Wilmer Ophthalmological Institute的支持信）。