Moldable tissue-sealant hydrogels were developed herein by combining the yield stress fluidity of a Carbomer and in situ cross-linking of 3-arm PEG-thiol (PEG-SH) and 4-arm PEG-acrylate (PEG-AC). The Carbomer was mixed with each PEG oligomer to form two aqueous precursors: Carbomer/PEG-SH and Carbomer/PEG-AC. The two hydrogel precursors exhibited sufficient yield stress (>100 Pa) to prevent dripping from their placement on the tissue surface. Moreover, these hydrogel precursors exhibited rapid restructuring when the shear strain was repeatedly changed. These rheological properties contribute to the moldability of these hydrogel precursors. After mixing these two precursors, they were converted from yield-stress fluids to chemically cross-linked hydrogels, Carbomer/PEG hydrogel, via thiol-Michael addition. The gelation time was 5.0 and 11.2 min at 37 and 25 °C, respectively. In addition, the Carbomer/PEG hydrogels exhibited higher cellular viability than the pure Carbomer. They also showed stable adhesiveness and burst pressure resistance to various tissues, such as the skin, stomach, colon, and cecum of pigs. The hydrogels showed excellent tissue sealing in a cecum ligation and puncture model in mice and improved the survival rate due to their tissue adhesiveness and biocompatibility. The Carbomer/PEG hydrogel is a potential biocompatible tissue sealant that surgeons can mold. It was revealed that the combination of in situ cross-linkable PEG oligomers and yield stress fluid such as Carbomer is effective for developing the moldable tissue sealant without dripping of its hydrogel precursors.

中文翻译：

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由可原位交联聚乙二醇通过硫醇-迈克尔加成和卡波姆组成的可成型组织密封剂水凝胶

本文通过结合卡波姆的屈服应力流动性和 3 臂 PEG-硫醇 (PEG-SH) 和 4 臂 PEG-丙烯酸酯 (PEG-AC) 的原位交联，开发了可成型的组织密封剂水凝胶。卡波姆与每种 PEG 低聚物混合，形成两种水性前体：卡波姆/PEG-SH 和卡波姆/PEG-AC。两种水凝胶前体表现出足够的屈服应力（>100 Pa），以防止它们在组织表面上滴落。此外，当剪切应变反复变化时，这些水凝胶前体表现出快速重组。这些流变特性有助于这些水凝胶前体的成型性。混合这两种前体后，通过硫醇-迈克尔加成，它们从屈服应力流体转化为化学交联水凝胶，卡波姆/PEG水凝胶。 37°C 和 25°C 下的凝胶时间分别为 5.0 分钟和 11.2 分钟。此外，卡波姆/PEG水凝胶比纯卡波姆表现出更高的细胞活力。它们还对猪的皮肤、胃、结肠和盲肠等多种组织表现出稳定的粘附性和耐爆破压力。该水凝胶在小鼠盲肠结扎和穿刺模型中表现出优异的组织密封性，并且由于其组织粘附性和生物相容性而提高了存活率。卡波姆/聚乙二醇水凝胶是一种潜在的生物相容性组织密封剂，外科医生可以对其进行成型。结果表明，原位交联 PEG 低聚物和屈服应力流体（如卡波姆）的组合可有效开发可成型的组织密封剂，且不会滴落其水凝胶前体。