Bioinspired Hydrogel Adhesives for Next-Generation Bioglues with Multifunctionality

背景：生物胶正在积极发展，以取代缝合线缝合伤口。然而，现有的生物胶要么机械性能弱，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报告了一种具有优异附着力和机械性能的仿生坚韧水凝胶粘合剂家族。它们可以用于开发下一代生物胶，但仍然存在三个主要挑战：(1)现有系统的设计和化学性质与注射器注射和原位凝胶不兼容；(2)胶粘剂的高应变率响应和疲劳断裂机理有待进一步研究；(3)功能仅限于机械支持（粘合分离组织或密封），而缺乏生物降解和药物传递功能。******计划：该项目旨在为下一代多功能生物胶设计仿生注射型坚韧水凝胶粘合剂。这种生物胶可以通过注射器注射输送，在原位形成坚硬的基质，与组织紧密结合，并进行可控的生物降解。它们可以代替缝合线，释放治疗药物，以促进伤口愈合。短期目标包括：(1)开发具有新型粘合剂设计，点击化学和降解反应的坚韧生物胶；(2)研究生物胶的组织粘附机理；(3)探索其在给药、伤口愈合、吸能等方面的应用。我们的长期愿景是利用具有优异生物力学性能的软质生物材料改善软性动态组织的保健。除了伤口愈合，生物胶还可以为软骨、肌腱和声带的修复和再生提供有效的治疗方法。该课程将为研究生和本科生提供广泛的跨学科知识和技能。******影响：该项目具有创新性。它将展示第一种具有点击化学和可降解性的坚韧水凝胶，一种模仿鼻涕虫黏液的新型可注射水凝胶粘合剂的仿生设计，以及对组织粘附和水凝胶粘合剂的高应变率力学的新理解。这个项目将产生社会、技术和经济影响。这将代表着仿生学的一大进步，并对广泛的社区产生影响。坚韧的生物胶可以改变手术胶的设计和应用，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。该项目将为PI在组织修复、机械转导和再生医学方面的长期研究奠定基础。PI将与生物医药公司和医院合作，探索将这些材料转化为医疗保健产品，包括手术胶和伤口敷料，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.