Zheng Yuting, Baidya Avijit, Annabi Nasim
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, 90095, United States.
Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, United States.
Bioact Mater. 2023 Jul 17;29:214-229. doi: 10.1016/j.bioactmat.2023.06.007. eCollection 2023 Nov.
Designing adhesive hydrogels with optimal properties for the treatment of injured tissues is challenging due to the tradeoff between material stiffness and toughness while maintaining adherence to wet tissue surfaces. In most cases, bioadhesives with improved mechanical strength often lack an appropriate elastic compliance, hindering their application for sealing soft, elastic, and dynamic tissues. Here, we present a novel strategy for engineering tissue adhesives in which molecular building blocks are manipulated to allow for precise control and optimization of the various aforementioned properties without any tradeoffs. To introduce tunable mechanical properties and robust tissue adhesion, the hydrogel network presents different modes of covalent and noncovalent interactions using -hydroxysuccinimide ester (NHS) conjugated alginate (Alg-NHS), poly (ethylene glycol) diacrylate (PEGDA), tannic acid (TA), and Fe ions. Through combining and tuning different molecular interactions and a variety of crosslinking mechanisms, we were able to design an extremely elastic (924%) and tough (4697 kJ/m) multifunctional hydrogel that could quickly adhere to wet tissue surfaces within 5 s of gentle pressing and deform to support physiological tissue function over time under wet conditions. While Alg-NHS provides covalent bonding with the tissue surfaces, the catechol moieties of TA molecules synergistically adopt a mussel-inspired adhesive mechanism to establish robust adherence to the wet tissue. The strong adhesion of the engineered bioadhesive patch is showcased by its application to rabbit conjunctiva and porcine cornea. Meanwhile, the engineered bioadhesive demonstrated painless detachable characteristics and biocompatibility. Additionally, due to the molecular interactions between TA and Fe, antioxidant and antibacterial properties required to support the wound healing pathways were also highlighted. Overall, by tuning various molecular interactions, we were able to develop a single-hydrogel platform with an "all-in-one" multifunctionality that can address current challenges of engineering hydrogel-based bioadhesives for tissue repair and sealing.
设计具有最佳性能的粘性水凝胶用于治疗受伤组织具有挑战性，因为在保持对湿组织表面的粘附力的同时，材料的硬度和韧性之间存在权衡。在大多数情况下，机械强度提高的生物粘合剂通常缺乏适当的弹性顺应性，这阻碍了它们在密封柔软、有弹性和动态组织中的应用。在这里，我们提出了一种工程化组织粘合剂的新策略，其中操纵分子构建块以实现对上述各种特性的精确控制和优化，而无需任何权衡。为了引入可调的机械性能和强大的组织粘附力，水凝胶网络使用N-羟基琥珀酰亚胺酯（NHS）共轭藻酸盐（Alg-NHS）、聚（乙二醇）二丙烯酸酯（PEGDA）、单宁酸（TA）和铁离子呈现不同的共价和非共价相互作用模式。通过组合和调节不同的分子相互作用和各种交联机制，我们能够设计出一种极具弹性（924%）和坚韧（4697 kJ/m）的多功能水凝胶，该水凝胶在轻轻按压5秒内即可快速粘附到湿组织表面，并在湿条件下随时间变形以支持生理组织功能。虽然Alg-NHS与组织表面提供共价键合，但TA分子的儿茶酚部分协同采用受贻贝启发的粘附机制，以建立对湿组织的强大粘附力。工程化生物粘附贴片的强粘附力通过其在兔结膜和猪角膜上的应用得到展示。同时，工程化生物粘合剂表现出无痛可拆卸特性和生物相容性。此外，由于TA和Fe之间的分子相互作用，还突出了支持伤口愈合途径所需的抗氧化和抗菌特性。总体而言，通过调节各种分子相互作用，我们能够开发出一个具有“一体化”多功能性的单一水凝胶平台，该平台可以应对目前基于水凝胶的生物粘合剂用于组织修复和密封的工程挑战。
