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）：胶原蛋白用于各种医疗应用，从止血材料和生物相容性涂层到药物输送和组织工程。传统上，胶原蛋白被用作被动（但生物相容性）材料，保护受伤部位并支持愈合过程。今天，胶原蛋白作为生物活性支架，可以为特定组织的形成提供理想的环境，这是一个新的兴趣。这导致了将生物活性成分（如生长因子、抗微生物剂或细胞排斥剂）固定到天然胶原蛋白上的广泛兴趣。在这个建议中，我们希望研究非化学固定胶原模拟肽（CMP）和CMP衍生物的胶原支架，并探讨其作为一种新的胶原修饰技术的微血管工程的目标。 胶原蛋白模拟肽（CMP）是通常少于30个氨基酸的肽，由已知的解旋三聚体（例如ProHypGly）的多聚体组成。它们在确定天然胶原的结构和稳定性方面非常有用，并且它们的胶原样三螺旋结构和可逆缔合（熔融）行为在文献中有记载。在我们以前的研究中，我们发现在受控的热条件下，CMPs可以与胶原膜（I型）结合。 本研究的主要目的是进一步了解CMP-胶原相互作用，确定在生理或接近生理条件下表现出有效和可逆结合胶原的最佳CMP结构，并证明聚（乙二醇）-CMP缀合物在控制2D和3D胶原支架中的内皮细胞（艾德）组织中的实际用途。从长远来看，我们希望将这种方法发展成一种更通用的胶原蛋白修饰方法，可以为血管和眼部手术后的并发症提供新的解决方案，并为传统的胶原蛋白基生物材料增加治疗活性（参见约翰霍普金斯医学院威尔默眼科研究所的支持信）。