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

描述（由申请人提供）：一种基于贻贝黏附蛋白的可生物降解、防水组织黏附剂的开发伤口愈合一直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关闭，以确保伤口及时愈合，防止感染、伤口裂开、伤口关闭线形成窦性等并发症。虽然传统的缝合和吻合器是最常用的方法，但在某些情况下，这些伤口闭合装置可能不理想，需要使用组织粘合剂。由于组织粘胶剂需要具有生物相容性，可在水/生理环境中粘附，并可生物降解为无毒副产物，因此很难进行工程设计。虽然FDA最近批准了两种组织粘合剂在美国的某些应用，科学家们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，仍有很大的需要改进手术胶。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。在动荡的盐水环境中，贻贝可以通过释放迅速变硬的粘附蛋白，将自己固定在各种表面上。在这些黏合剂中发现的最有趣的成分之一是相对不寻常的氨基酸，3,4-二氢氧基苯丙氨酸（DOPA），它被认为是这些黏合剂蛋白抗湿粘附和内聚硬化的原因。含有多巴的粘合剂，无论是天然的还是合成的，都能与从生物组织到各种金属的表面紧密结合。在开发一种新的组织粘合剂时，我们将DOPA独特的粘合和内聚性能与生物相容性和可生物降解的聚合物骨架结合起来，创造出一种新型的可降解和防水的组织粘合剂。本提案概述了一种以DOPA修饰的可水解聚乙二醇（PEG）为基础的聚合物的合成和表征。通过改变起始材料PEG的分子量，我们希望提高粘合剂的内聚性能和整体粘接强度，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水的功能的可行性。有效的外科胶粘剂在简化复杂的外科手术程序和缩短手术时间方面比传统的伤口闭合设备具有优势，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，成功的组织粘接剂很难设计。本文描述了一种新型可生物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.