Biomimetic Tissue Adhesive with Mechanically Tough Hydrogel Support

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传统外科手术的重要目标。此外，手术重新连接损伤组织对于恢复其结构和功能是必不可少的。虽然软组织的不连续性传统上是用机械穿孔装置（如缝合线、大头针和订书钉）固定的，但这些装置也是并发症的来源，如组织创伤、慢性疼痛和不适，以及局部应力集中，这些都可能导致修复失败。组织粘接剂可以潜在地简化复杂的程序，减少手术时间，并最大限度地减少创伤。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。现有的组织粘接剂粘接强度弱（如纤维蛋白胶）和生物相容性差（如氰基丙烯酸酯），限制了它们在外科手术中的潜在应用。该项目的长期目标是开发具有强大粘合强度和与天然组织相匹配的生物力学性能的组织粘合剂，以修复常规经历大，重复负荷的组织（例如软骨，肌腱和韧带）。本提案的目的是确定具有海洋粘附部分的生物相容性和韧性水凝胶功能化的可行性，这将导致一种具有更高粘附强度的新型生物粘合剂。该提案的中心假设是，提高的大块材料韧性与强防水界面结合强度的最佳组合将产生具有优越的组织胶粘剂

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.