Effect of Cross-Linkers on Mussel- and Elastin-Inspired Adhesives on Physiological Substrates
Effect of Cross-Linkers on Mussel- and Elastin-Inspired Adhesives on Physiological Substrates
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DOI：
10.1021/acsabm.1c01095
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发表时间：
2022-02-21
影响因子：
4.7
通讯作者：
Liu, Julie C.
中科院分区：
文献类型：
--
作者：
Hollingshead, Sydney;Torres, Jessica E.;Liu, Julie C.
手术粘合剂可用于伤口闭合，因为它们降低了与缝合和斯台普斯相关的感染和疼痛风险。然而，没有市售的用于软组织伤口闭合的外科粘合剂。为了有效，软组织粘合剂必须是柔软和柔性的、强内聚性和粘合性的、生物相容的并且在潮湿环境中有效。为了解决这些标准，我们从弹性蛋白质的弹性和弹性以及海洋贻贝的粘合剂中汲取灵感。由于弹性蛋白样多肽（ELP）的弹性和生物相容性，我们将其用作粘合剂材料的骨架。一种贻贝启发的粘合剂分子，L-3，4-二羟基苯丙氨酸（DOPA），被纳入到粘合剂赋予湿固化粘合。在这项研究中，命名为YKV的ELP被设计为包括酪氨酸残基和赖氨酸残基，其含有胺基。通过酪氨酸残基酶促转化为多巴，产生了YKV的修饰版本，称为mYKV。将ELP与硝酸铁（III）、高碘酸钠和/或三（羟甲基）膦（THP）交联剂组合，以研究DOPA和基于胺的交联对温暖潮湿环境中猪皮上的粘附强度和固化时间的影响。将DOPA掺入ELP中可使粘合强度增加2.5倍，并降低失效率。铁交联剂在DOPA的存在下改善了粘附性。THP增加了所有测试的蛋白质的粘附，即使在没有多巴的情况下。在单一制剂中使用多种交联剂没有显著改善粘附性。在猪皮肤上具有最高性能的粘合剂（硝酸铁与mYKV混合以及THP与YKV或mYKV混合）具有比商业密封剂高10-18倍的粘合力，并且在10分钟内达到可观的粘合强度。
Surgical adhesives can be useful in wound closure because they reduce the risk of infection and pain associated with sutures and staples. However, there are no commercially available surgical adhesives for soft tissue wound closure. To be effective, soft tissue adhesives must be soft and flexible, strongly cohesive and adhesive, biocompatible, and effective in a moist environment. To address these criteria, we draw inspiration from the elasticity and resilience of elastin proteins and the adhesive of marine mussels. We used an elastin-like polypeptide (ELP) for the backbone of our adhesive material due to its elasticity and biocompatibility. A mussel-inspired adhesive molecule, L-3,4-dihydroxyphenylalanine (DOPA), was incorporated into the adhesive to confer wet-setting adhesion. In this study, an ELP named YKV was designed to include tyrosine residues and lysine residues, which contain amine groups. A modified version of YKV, named mYKV, was created through enzymatic conversion of tyrosine residues into DOPA. The ELPs were combined with iron(III) nitrate, sodium periodate, and/or tris(hydroxymethyl)phosphine (THP) cross-linkers to investigate the effect of DOPA- and amine-based cross-linking on adhesion strength and cure time on porcine skin in a warm, humid environment. Incorporation of DOPA into the ELP increased adhesive strength by 2.5 times and reduced failure rates. Iron cross-linkers improved adhesion in the presence of DOPA. THP increased adhesion for all proteins tested even in the absence of DOPA. Using multiple cross-linkers in a single formulation did not significantly improve adhesion. The adhesives with the highest performance (iron nitrate mixed with mYKV and THP mixed with YKV or mYKV) on porcine skin had 10-18 times higher adhesion than a commercial sealant and reached appreciable adhesive strength within 10 min.