Development of a Biodegradable, Water-resistant Tissue Adhesive based on Mussel A

基于贻贝 A 的可生物降解、防水组织粘合剂的开发

• 批准号: 7269544
• 负责人: Bruce P Lee
• 金额: $ 9.98万
• 依托单位: NERITES CORPORATION
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2007-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7269544
• 关键词: Adhesions; Adhesives; Amino Acids; Binding; Biocompatible; Biological; Breathing; Closure; Complex; Development; Devices; Engineering; Ensure; Environment; Esters; Evaluation; Glues; Marines; Mechanics; Medical; Metals; Methods; Molecular Weight; Mussels; Nature; Operative Surgical Procedures; Phase I Clinical Trials; Physiological; Polyethylene Glycols; Polymers; Property; Proteins; Range; Resistance; Saline; Scientist; Sinus; Surface; Surgical sutures; Time; Tissue Adhesives; Tissues; United States Food and Drug Administration; Vertebral column; Water; Wound Healing; Wound Infection; adhesive polymer; adhesive protein (mussel); aqueous; base; biomaterial compatibility; design; desire; improved; new technology; novel; research study; wound

DESCRIPTION (provided by applicant): Development of a Biodegradable, Water-Resistant Tissue Adhesive based on Mussel Adhesive Proteins Wound closure continues to be one of the most important parts of all surgical procedures. Every operation requires proper wound closure to ensure timely wound healing and protection from complications such as infection, wound dehiscence, and sinus formation in the wound closure line. Although traditional suturing and stapling are the most commonly used methods, in certain cases these wound closure devices may not be ideal and the use of a tissue adhesive is desired. Because tissue adhesives are required to be biocompatible, adhere in an aqueous/physiological environment, and biodegradable into nontoxic byproducts, they have proved difficult to engineer. Although the FDA has recently approved two tissue adhesives for certain applications in the U.S. and scientists continue to develop new adhesives and sealants, none of them have yet been proven ideal. Thus, there remains a great need for improved surgical glues. Nature often provides inspiration for the development of new technologies, and adhesive proteins secreted by marine mussels provide ample inspiration for the development of new medical adhesives. Marine mussels can anchor themselves to various surfaces in a turbulent, saline environment through the release of adhesive proteins that harden rapidly. One of the most intriguing components found in these adhesives is the relatively unusual amino acid, 3,4-dihidroxyphenylalanine (DOPA), which is believed to be responsible for both moisture-resistant adhesion and cohesive hardening of these adhesive proteins. DOPA-containing adhesives, both natural and synthetic, have been shown to bind strongly to surfaces ranging from biological tissues to various metals. In developing a new tissue adhesive, we are combining the unique adhesive and cohesive properties of DOPA with a biocompatible and biodegradable polymeric backbone to create a novel degradable and water-resistant tissue adhesive. This proposal outlines the synthesis and characterization of a hydrolysable polyethylene glycol (PEG)-based polymer modified with DOPA. By changing the molecular weights of the starting material PEG, we hope to enhance the cohesive properties and overall adhesive strength over adhesives we have developed in the past. Experiments will be performed to determine the feasibility of manufacturing this adhesive polymer and of its function as a medical glue. Development ofa Biodegradable, Water-Resistant Tissue Adhesive based on Mussel Adhesive Proteins Effective surgical glues have advantages over traditional wound closure devices in simplifying complex surgical procedures and in reducing surgical time, which can expediteproper wound healing. However, due to stringent design requirements such as water-resistant adhesion, biocompatibility, and degradability, successful tissue adhesives have been difficult to engineer. The development and evaluation of a new biodegradable tissue adhesive that combines a marine adhesive moiety and a biocompatible synthetic polymer is described here.

描述（由申请人提供）：基于贻贝粘合剂蛋白质伤口封闭的可生物降解，防水组织粘合剂的发展仍然是所有外科手术程序中最重要的部分之一。每个手术都需要适当的伤口闭合，以确保伤口闭合线中的感染，伤口裂开和鼻窦形成等并发症的及时伤口愈合和保护。尽管传统的缝合和钉钉是最常用的方法，但在某些情况下，这些伤口闭合装置可能不是理想的，并且需要使用组织粘合剂。由于组织粘合剂必须具有生物相容性，因此在水性/生理环境中粘附，并可以生物降解成无毒的副产品，因此事实证明，它们很难设计。尽管FDA最近批准了两种用于美国某些应用的组织胶粘剂，并且科学家继续开发新的粘合剂和密封剂，但尚未被证明是理想的。因此，仍然需要改善手术胶水。大自然通常为开发新技术提供灵感，而海洋贻贝分泌的粘合剂蛋白为开发新的医学粘合剂提供了充足的灵感。海洋贻贝可以通过迅速变硬的粘合剂蛋白释放在湍流的盐水环境中将自己固定在各种表面上。这些粘合剂中发现的最有趣的成分之一是相对不寻常的氨基酸，3,4-二羟基苯基丙氨酸（DOPA），据信这既是耐水性粘合剂和凝聚力硬化的构成，又是对这些粘附蛋白的凝聚力硬化的原因。含有天然和合成的含DOPA的粘合剂已被证明与从生物组织到各种金属的表面强烈结合。在开发一种新的组织粘合剂时，我们将DOPA的独特粘合剂和内粘性特性与可生物相容性和可生物降解的聚合物主链结合在一起，以创建一种新型的可降解且耐水的组织粘合剂。该建议概述了用DOPA修饰的基于水解聚乙烯（PEG）的聚合物的合成和表征。通过更改起始材料钉的分子量，我们希望增强与过去开发的粘合剂相对于粘合剂的凝聚力和整体粘合强度。将进行实验，以确定生产这种粘合剂聚合物及其作为医疗胶的功能的可行性。基于贻贝粘合剂蛋白的可生物降解，耐水组织粘合剂的有效手术胶具有比传统伤口闭合装置的优势，可以简化复杂的手术手术程序和减少手术时间，从而可以进行急诊疗法。但是，由于严格的设计要求，例如防水粘附，生物相容性和降解性，因此很难设计成功的组织粘合剂。此处描述了新型可生物降解组织粘合剂的开发和评估，该组织粘合剂结合了海洋粘合部分和生物相容性合成聚合物。