由于在保持对湿组织表面的粘附性的同时在材料刚度和韧性之间进行权衡,设计具有用于治疗损伤组织的最佳性质的粘合剂水凝胶是具有挑战性的。在大多数情况下,具有改善的机械强度的生物粘合剂通常缺乏适当的弹性顺应性,阻碍其密封软的应用,弹性,和动态组织。这里,我们提出了一种用于工程组织粘合剂的新策略,其中分子构建块被操纵以允许精确控制和优化各种上述性质,而无需任何权衡。为了引入可调的机械性能和坚固的组织粘附,使用N-羟基琥珀酰亚胺酯(NHS)缀合的藻酸盐(Alg-NHS),水凝胶网络呈现共价和非共价相互作用的不同模式,聚(乙二醇)二丙烯酸酯(PEGDA),单宁酸(TA),和Fe3+离子。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(4697kJ/m3)的多功能水凝胶,其可以在温和按压的5秒内快速粘附到湿组织表面,并在潮湿条件下随着时间的推移变形以支持生理组织功能。虽然Alg-NHS提供与组织表面的共价键合,TA分子的儿茶酚部分协同地采用贻贝启发的粘附机制以建立对湿组织的牢固粘附。工程生物粘附贴片的强粘附性通过其在兔结膜和猪角膜上的应用得到了证明。同时,工程生物粘合剂表现出无痛的可分离特性和体外生物相容性。此外,由于TA和Fe3+之间的分子相互作用,还强调了支持伤口愈合途径所需的抗氧化和抗菌特性。总的来说,通过调整各种分子相互作用,我们能够开发一个具有"一体化"多功能的单水凝胶平台,可以解决当前在工程基于水凝胶的生物粘合剂用于组织修复和密封的挑战.
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 N-hydroxysuccinimide ester (NHS) conjugated alginate (Alg-NHS), poly (ethylene glycol) diacrylate (PEGDA), tannic acid (TA), and Fe3+ 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/m3) 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 in vitro biocompatibility. Additionally, due to the molecular interactions between TA and Fe3+, 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.