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

描述（由申请人提供）：基于贻贝粘附蛋白的生物可降解、防水组织粘合剂的开发伤口闭合仍然是所有外科手术中最重要的部分之一。每次手术都需要适当的伤口闭合，以确保伤口及时愈合，并防止感染、伤口裂开和伤口闭合线窦道形成等并发症。尽管传统的缝合和缝合是最常用的方法，但在某些情况下，这些伤口闭合装置可能并不理想，并且需要使用组织粘合剂。因为组织粘合剂需要是生物相容的，在水性/生理环境中粘附，并且可生物降解成无毒副产物，所以它们已被证明难以工程化。尽管FDA最近批准了两种用于美国某些应用的组织粘合剂，科学家们也在继续开发新的粘合剂和密封剂，但没有一种被证明是理想的。因此，仍然非常需要改进的外科胶水。大自然常常为新技术的发展提供灵感，海洋贻贝分泌的粘附蛋白为新型医用粘合剂的开发提供了充足的灵感。海洋贻贝可以通过释放迅速变硬的粘附蛋白质，在湍流的盐水环境中将自己锚在各种表面上。在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，3，4-二羟基苯丙氨酸（DOPA），据信这是这些粘合剂蛋白质的防潮粘合和内聚硬化的原因。含DOPA的粘合剂，无论是天然的还是合成的，都已显示出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，我们将多巴独特的粘合和内聚特性与生物相容性和可生物降解的聚合物骨架相结合，以创造一种新型的可降解和防水的组织粘合剂。该提案概述了DOPA改性的可水解聚乙二醇（PEG）基聚合物的合成和表征。通过改变起始材料PEG的分子量，我们希望增强内聚性能和整体粘合强度，超过我们过去开发的粘合剂。将进行实验以确定制造这种粘合剂聚合物及其作为医用胶的功能的可行性。基于贻贝粘附蛋白的生物可降解、防水组织粘合剂的开发有效的外科粘合剂在简化复杂的外科手术程序和减少手术时间方面优于传统的伤口闭合装置，这可以加速伤口的适当愈合。然而，由于严格的设计要求，如防水粘合，生物相容性和可降解性，成功的组织粘合剂一直难以工程。本文介绍了一种新的生物可降解组织粘合剂的开发和评价，该粘合剂结合了海洋粘合剂部分和生物相容性合成聚合物。

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.