Biomimetic Tissue Adhesive with Mechanically Tough Hydrogel Support

具有机械强度的水凝胶支撑的仿生组织粘合剂

• 批准号: 8434410
• 负责人: Bruce P Lee
• 金额: $ 34.45万
• 依托单位: MICHIGAN TECHNOLOGICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8434410
• 关键词: Adhesions; Adhesives; Anastomosis - action; Animals; Award; Binding; Biocompatible; Biological; Biomechanics; Biomimetics; Cardiovascular system; Cartilage; Cell Culture Techniques; Cells; Cicatrix; Complex; Connective Tissue; Cyanoacrylates; Data; Defect; Development; Devices; Drug Delivery Systems; Engineering; Evaluation; Exhibits; Failure; Fibrin Tissue Adhesive; Fracture; Funding; Future; Goals; Growth; Healed; Health; Histology; Hydrogels; Hydrolysis; Implant; In Situ; In Vitro; Inflammatory Response; Intestines; Lead; Ligaments; Link; Marines; Mechanics; Metals; Natural regeneration; Operative Surgical Procedures; Outcome; Pain; Patients; Physiological; Play; Polymers; Preparation; Procedures; Property; Proteins; Rattus; Rehabilitation therapy; Relative (related person); Research; Resistance; Resources; Role; Secure; Source; Stress; Structure; Surface; Surgical sutures; Tendon structure; Testing; Time; Tissue Adhesives; Tissue Engineering; Tissues; Training; Trauma; United States National Institutes of Health; Water; Weight-Bearing state; Work; biomaterial compatibility; bone; cartilage repair; chronic pain; design; experience; graduate student; healing; implantation; injured; interfacial; minimally invasive; novel; programs; public health relevance; repaired; research study; restoration; sample fixation; scaffold; soft tissue; subcutaneous; tissue repair; tissue trauma; undergraduate student; wound

DESCRIPTION (provided by applicant): Rapid and effective wound closure remains an important goal of virtually all modern endoscopic and conventional surgical procedures. Additionally, surgical reconnection of injured tissues is essential for restoration of their structre and function. While, the discontinuity in soft tissues is traditionally secured with mechanical perforating devices (e.g., sutures, tacks, and staples), these devices are also a source of complications, such as tissue trauma, chronic pain and discomfort, and localized stress concentrations which can lead to failure of the repair. Tissue adhesives can potentially simplify complex procedures, reduce surgery time, and minimize trauma. However, due to stringent design requirements such as water-resistant adhesion, biocompatibility, and degradability, successful tissue adhesives have been difficult to engineer. Existing tissue adhesives are hampered by weak adhesive strength (i.e., fibrin glue) and poor biocompatibility (i.e., cyanoacrylate), which limit their potential applications in surgery. The long term goal of this project is to develop tissue adhesives with strong adhesive strength and biomechanical properties matching those of native tissue to repair tissues that routinely experience large, repeated loads (e.g., cartilage, tendon, and ligament). The objective of this proposal is to establish the feasibility that functionalizing biocompatible and tough hydrogel with marine adhesive moiety will lead to a novel bioadhesive with elevated adhesive strength. The central hypothesis of this proposal is that an optimal combination of elevated bulk material toughness with strong water-resistant interfacial binding strength will yield a tissue adhesive with superior adhesive properties (i.e., work of adhesion). The work to be accomplished in this proposal includes: 1) functionalize a tough hydrogel with water-resistant adhesive moiety and to investigate its adhesive properties and rate of degradation in vitro; 2) determine preliminary biocompatibility of the adhesive using in vitro cell culture and subcutaneous implantation in rat. The expected outcomes include a biocompatible tissue adhesive with significantly higher adhesive strength when compared to existing tissue adhesives. Successful completion of the proposed work will lead to follow-on projects aimed at incorporating other desirable physical and biological properties into the adhesive such as in situ curing (e.g., minimally invasive delivery and conformity to a tissue defect), in situ activation (e.g., activation upon contact with wetted tissue to minimize the need for complex preparation prior to use), bioactivity (e.g., cell binding, tissue in growth), and tailoring the adhesive to a specific application (e.g., tendon repair, cartilage repair, ligament repair, tissue engineering scaffold fixation, suture-less anastomosis of cardiovascular or bowel tissues, drug delivery, etc.). This AREA award will provide the PI with resources to train undergraduate and graduate students, obtain data for future NIH funding, and build a nationally-recognized graduate program.

描述（由申请人提供）：快速有效的伤口闭合仍然是几乎所有现代内窥镜和常规手术程序的重要目标。此外，受伤组织的手术重新连接对于恢复其肿瘤和功能至关重要。尽管传统上，软组织中的不连续性是用机械穿孔设备（例如缝合线，大头钉和钉书钉）固定的，但这些设备也是并发症的来源，例如组织创伤，慢性疼痛和不适，以及局部的应力浓度，可能导致修复失败。组织粘合剂可以潜在地简化复杂的程序，减少手术时间并最大程度地减少创伤。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。现有的组织粘合剂受到弱粘合强度（即纤维蛋白胶）和差的生物相容性（即氰基丙烯酸酯）的阻碍，从而限制了它们在手术中的潜在应用。该项目的长期目标是开发具有较强粘合强度和生物力学特性的组织粘合剂，该特性与天然组织的组织粘合剂相匹配，以修复通常会经历大型重复载荷的组织（例如软骨，肌腱和韧带）。该提案的目的是确定可行性，即用海洋粘合一部分功能化生物相容性和坚硬的水凝胶将导致一种新型的生物粘附，并具有升高的粘附力。该提议的中心假设是，高架材料韧性与强烈防水界面结合强度的最佳组合将产生具有优质的组织粘合剂 粘合特性（即粘附的工作）。在该提案中要完成的工作包括：1）用耐水粘合性部分功能化坚硬的水凝胶，并研究其粘合性特性和体外降解速率； 2）确定使用体外细胞培养和皮下植入大鼠的粘合剂的初步生物相容性。与现有的组织粘合剂相比，预期的结果包括具有更高粘合力的生物相容性组织粘合剂。成功完成拟议的工作将导致旨在将其他理想的物理和生物学特性纳入粘合剂中，例如原位固化（例如，微创递送和符合组织缺陷的微创递送和一致性），原位激活（例如，在与湿组织接触以最小化复杂性，都可以使用复合物，） 生长组织），并根据特定的应用调整粘合剂（例如，肌腱修复，软骨修复，韧带修复，组织工程支架固定，无缝合的无缝合吻合 心血管或肠组织，药物输送等）。该地区奖将为PI提供资源来培训本科生和研究生，获取未来的NIH资金数据，并建立一个全国认可的研究生计划。