Zheng Yuting, Shariati Kaavian, Ghovvati Mahsa, Vo Steven, Origer Nolan, Imahori Taichiro, Kaneko Naoki, Annabi Nasim
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.
David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, CA 90095, USA.
Biomaterials. 2023 Oct;301:122240. doi: 10.1016/j.biomaterials.2023.122240. Epub 2023 Jul 12.
Controlling traumatic bleeding from damaged internal organs while effectively sealing the wound is critical for saving the lives of patients. Existing bioadhesives suffer from blood incompatibility, insufficient adhesion to wet surfaces, weak mechanical properties, and complex application procedures. Here, we engineered a ready-to-use hemostatic bioadhesive with ultra-strengthened mechanical properties and fatigue resistance, robust adhesion to wet tissues within a few seconds of gentle pressing, deformability to accommodate physiological function and action, and the ability to stop bleeding efficiently. The engineered hydrogel, which demonstrated high elasticity (>900%) and toughness (>4600 kJ/m), was formed by fine-tuning a series of molecular interactions and crosslinking mechanisms involving N-hydroxysuccinimide (NHS) conjugated alginate (Alg-NHS), poly (ethylene glycol) diacrylate (PEGDA), tannic acid (TA), and Fe ions. Dual adhesive moieties including mussel-inspired pyrogallol/catechol and NHS synergistically enhanced wet tissue adhesion (>400 kPa in a wound closure test). In conjunction with physical sealing, the high affinity of TA/Fe for blood could further augment hemostasis. The engineered bioadhesive demonstrated excellent in vitro and in vivo biocompatibility as well as improved hemostatic efficacy as compared to commercial Surgicel®. Overall, the hydrogel design strategy described herein holds great promise for overcoming existing obstacles impeding clinical translation of engineered hemostatic bioadhesives.
在有效封闭伤口的同时控制受损内脏器官的创伤性出血对于挽救患者生命至关重要。现有的生物粘合剂存在血液不相容性、对湿表面的粘附力不足、机械性能较弱以及应用程序复杂等问题。在此，我们设计了一种即用型止血生物粘合剂，它具有超强的机械性能和抗疲劳性，在轻轻按压几秒钟内就能牢固地粘附在湿组织上，具有可变形性以适应生理功能和作用，并且能够有效止血。这种经过设计的水凝胶表现出高弹性（>900%）和韧性（>4600 kJ/m），它是通过微调一系列涉及N-羟基琥珀酰亚胺（NHS）共轭藻酸盐（Alg-NHS）、聚（乙二醇）二丙烯酸酯（PEGDA）、单宁酸（TA）和铁离子的分子相互作用和交联机制而形成的。包括贻贝启发的邻苯三酚/儿茶酚和NHS在内的双重粘附基团协同增强了对湿组织的粘附力（在伤口闭合测试中>400 kPa）。与物理封闭相结合，TA/Fe对血液的高亲和力可进一步增强止血效果。与市售的Surgicel®相比，这种经过设计的生物粘合剂表现出优异的体外和体内生物相容性以及更高的止血效果。总体而言，本文所述的水凝胶设计策略在克服阻碍工程化止血生物粘合剂临床转化的现有障碍方面具有巨大潜力。
