In Situ Clickable Purely Zwitterionic Hydrogel for Peritoneal Adhesion Prevention,Chemistry of Materials

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In Situ Clickable Purely Zwitterionic Hydrogel for Peritoneal Adhesion Prevention
Chemistry of Materials ( IF 7.2 ) Pub Date : 2020-07-13 , DOI: 10.1021/acs.chemmater.0c00889
Qi Guo ₁ , Hong Sun ₂ , Xiaojun Wu ₁ , Zhiwen Yan ₂ , Chenjue Tang ₁ , Zhihui Qin ₁ , Mengmeng Yao ₁ , Pengcheng Che ₂ , Fanglian Yao _{1,

3,

4} , Junjie Li _{1,

3}

Affiliation

Intraperitoneal adhesions are common and serious complications after surgery. Deposition of proteins and inflammatory response on an injured cecum are the main factors resulting in the formation of adhesion. In this study, purely zwitterionic hydrogels (Z-hydrogels) are developed using thiolated poly(sulfobetaine methacrylate-co-2-((2-hydroxyethyl)disulfanyl)ethyl methacrylate) [poly(SBMA-co-HDSMA)] as the network backbone and divinyl-functionalized sulfobetaine (BMSAB) as the zwitterionic cross-linker via the thiol–ene click reaction. To improve the anti-inflammatory activity, cefoxitin sodium is loaded into Z-hydrogels (Z/C-hydrogel) to construct the physical barrier/drug system. The gelation time, mechanical behavior, and swelling ratio of the prepared Z-hydrogel can be modulated via adjusting the SBMA/HDSMA ratio in the copolymer. Moreover, they not only exhibit excellent resistance to protein and fibroblast adhesion but also show good biocompatibility and hemocompatibility. To assess its anti-adhesion effects in vivo, the Z-hydrogel is injected on the injured cecum surface using a rat model of sidewall defect-cecum abrasion. The results show that the Z-hydrogel can completely cover the irregular cecum surface and effectively suppress the formation of postoperative adhesion via reducing protein deposition and resisting fibroblast adhesion. Moreover, the introduction of cefoxitin sodium decreases the inflammatory response after surgery, thus further improving the anti-adhesion effect. Overall, we suggest that the Z-hydrogel is a promising candidate for the prevention of a postsurgical peritoneal adhesion.

中文翻译：

原位可点击的纯两性离子水凝胶用于预防腹膜粘连

腹腔粘连是术后常见的严重并发症。蛋白质的沉积和在受伤的盲肠上的炎症反应是导致粘连形成的主要因素。在这项研究中，纯粹的两性离子水凝胶（Z-水凝胶）使用硫醇化聚显影（磺基甜菜碱丙烯酸甲酯-共-2 - （（2-羟基乙基）二硫基）乙基甲基丙烯酸酯）[聚（SBMA-共-HDSMA）]作为网络主干，通过硫醇-烯点击反应将二乙烯基官能化的磺基甜菜碱（BMSAB）作为两性离子交联剂。为了提高抗炎活性，将头孢西丁钠装入Z-水凝胶（Z / C-水凝胶）中以构建物理屏障/药物系统。可以通过调节共聚物中的SBMA / HDSMA比来调节制备的Z-水凝胶的胶凝时间，机械性能和溶胀比。此外，它们不仅表现出对蛋白质和成纤维细胞粘附的优异抵抗力，而且还表现出良好的生物相容性和血液相容性。为了评估其在体内的抗粘连作用，使用侧壁缺损-盲肠磨擦的大鼠模型将Z-水凝胶注入受伤的盲肠表面。结果表明，Z-水凝胶可以完全覆盖不规则的盲肠表面，并通过减少蛋白质沉积和抵抗成纤维细胞粘附而有效抑制术后粘连的形成。此外，头孢西丁钠的引入降低了手术后的炎症反应，从而进一步提高了抗粘连作用。总体而言，我们建议Z-水凝胶是预防术后腹膜粘连的有前途的候选者。

更新日期：2020-08-11

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