Bioinspired Hydrogel Adhesives for Next-Generation Bioglues with Multifunctionality

背景：Biogle正在积极开发以取代缝合伤口的缝线。然而，现有的生物胶要么机械上很弱，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报道了一系列具有生物灵感的坚韧水凝胶粘合剂，具有优异的粘附性和机械性能。它们可用于开发下一代生物粘合剂，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不兼容；(2)这些粘合剂的机理，包括高应变率响应和疲劳断裂，仍未被探索；(3)功能仅限于机械支持(粘合分离组织或密封)，而缺乏生物降解和药物输送功能。*计划：该项目旨在为下一代多功能生物胶粘剂设计生物灵感可注射坚韧水凝胶粘合剂。这种生物胶可以通过注射器注射，在原位形成坚韧的基质，与组织紧密结合，并进行受控的生物降解。他们可以更换缝合线并释放治疗药物来促进伤口愈合。短期目标包括：(1)开发具有新型粘接剂设计、点击化学和降解反应的坚韧生物胶体；(2)研究生物胶体的组织黏附机理；(3)探索其在药物输送、伤口愈合和能量吸收应用中的应用。长期的愿景是用具有优异生物力学性能的软性生物材料来改善软组织动态组织的保健。除了愈合伤口外，这种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：该计划具有创新性。它将展示第一个具有点击化学和可控制降解性的坚韧水凝胶，一种模仿鼻塞粘液的新型仿生注射水凝胶粘合剂设计，以及对水凝胶粘合剂的组织粘合和高应变率机理的新理解。这一计划将产生社会、技术和经济影响。它将代表着仿生学的一大进步，并影响到广泛的社区。这种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、药物输送和生物医疗设备。该计划将为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保健产品，包括手术胶和伤口敷料，以造福临床患者。

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.