Bioinspired Hydrogel Adhesives for Next-Generation Bioglues with Multifunctionality

背景：Bioglues正在积极开发中，以取代缝线用于伤口闭合。然而，现有的抗生素要么机械性能差，要么与细胞和组织不相容。生物灵感和水凝胶的最新进展有望克服这些挑战。PI报告了一系列具有上级粘附性和机械性能的生物启发坚韧水凝胶粘合剂。它们可用于开发下一代粘合剂，但仍存在三个主要挑战：（1）现有系统的设计和化学与注射器注射和原位凝胶化不相容;（2）这些粘合剂的力学，包括高应变率响应和疲劳断裂，仍未被探索;（3）功能仅限于机械支撑（粘合分离组织或密封），而缺少生物降解和药物递送功能。** 计划：该计划旨在为下一代多功能支架设计生物启发的可注射坚韧水凝胶粘合剂。这种明胶可以通过注射器注射递送，原位形成牢固结合到组织的坚韧基质，并进行受控的生物降解。它们可以取代缝线并释放治疗剂以改善伤口愈合。短期目标包括（1）开发具有新粘合剂设计、点击化学和降解反应的坚韧粘合剂;（2）研究粘合剂的组织粘附力学;（3）探索其在药物输送、伤口愈合和能量吸收应用中的用途。长期愿景是使用具有上级生物力学性能的软生物材料改善软动态组织的保健。除了伤口闭合外，该支架还可以为软骨、肌腱和声带的修复和再生的有效治疗铺平道路。该计划将为研究生和本科生提供广泛的跨学科知识和技能。影响：该方案具有创新性。它将提出第一个坚韧的水凝胶点击化学和可控的降解性，一种新型的仿生设计的可注射水凝胶粘合剂，模仿鼻涕虫粘液，和组织粘附和高应变率力学的水凝胶粘合剂的新认识。该计划将产生社会，技术和经济影响。它将代表仿生学的一大进步，并影响广泛的社区。这种坚韧的胶水可以改变外科胶水的设计和应用，并影响许多领域，包括伤口敷料、止血剂、密封剂、药物输送和生物医学设备。该计划将为PI在组织修复、机械传导和再生医学方面的长期研究奠定基础。PI将与生物医学公司和医院合作，探索将这些材料转化为医疗保健产品，包括外科胶水和伤口敷料，以使临床患者受益。

Background: Bioglues are under active development to replace sutures for wound closure. However, existing bioglues are either mechanically weak or incompatible with cells and tissues. Recent advances in bioinspiration and hydrogels promise to overcome these challenges. The PI reported a family of bioinspired tough hydrogel adhesives with superior adhesion and mechanical properties. They can be used to develop the next-generation bioglues, but there remain three primary challenges: (1) the design and chemistry of the existing systems is incompatible with syringe injection and in-situ gelation; (2) the mechanics of these adhesives, including high strain rate response and fatigue fracture, remains unexplored; (3) the functionality is limited to mechanical support (gluing separating tissues or sealing), whereas biodegradation and drug-delivery function is missing. ******Plan: This program is to design bioinspired injectable tough hydrogel adhesives for the next-generation multifunctional bioglues. Such bioglues can be delivered via syringe injection, form a tough matrix in-situ that bonds strongly to tissues, and undergo controlled biodegradation. They can replace sutures and release therapeutics to improve wound healing. The short-term objectives include (1) Developing tough bioglues with new adhesive design, click chemistry and degradation reactions; (2) Studying tissue-adhesion mechanics of bioglues; (3) Exploring their use in drug delivery, wound healing and energy-absorbing applications. The long-term vision is to improve the healthcare of soft dynamic tissues with soft biomaterials with superior biomechanical properties. Besides the wound closure, the bioglues can pave way for effective therapies for the repair and regeneration of cartilage, tendon, and vocal fold. This program will provide graduate and undergraduate students with extensive transdisciplinary knowledge and skills.******Impact: The program is innovative. It will present the first tough hydrogels with click chemistry and controlled degradability, a novel biomimetic design of injectable hydrogel adhesives that mimic the slug mucus, and a new understanding of tissue adhesion and high strain rate mechanics of hydrogel adhesives. This program will make social,technological and economic impacts. It will represent a big advance in biomimetics and impact a broad community. The tough bioglues can transform the design and application of surgical glues and impact many areas, including wound dressings, hemostats, sealants, drug delivery and biomedical devices. This program will set a foundation for the PI's long-term research in tissue repair, mechanotransduction and regenerative medicine. The PI will collaborate with biomedical companies and hospitals to explore translation of these materials into healthcare products, including surgical glues and wound dressings, to benefit patients in the clinic.