Fouling-resistant zwitterionic polymers for complete prevention of postoperative adhesion
Fouling-resistant zwitterionic polymers for complete prevention of postoperative adhesion
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DOI：
10.1073/pnas.2012491117
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发表时间：
2020-11
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影响因子：
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通讯作者：
Ershuai Zhang;Boyi Song;Yuanjie Shi;Hui Zhu;Xiangfei Han;Hong Du;Chengbiao Yang;Zhiqiang Cao-
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文献类型：
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作者：
Ershuai Zhang;Boyi Song;Yuanjie Shi;Hui Zhu;Xiangfei Han;Hong Du;Chengbiao Yang;Zhiqiang Cao-
术后腹膜粘连是几乎所有类型的腹部和骨盆手术的常见并发症，并导致许多医学问题。目前的抗粘连解决方案包括药物治疗和物理屏障，但效果不佳，只能在一定程度上缓解或减少粘连。在这里，我们展示了一种两性离子聚合物溶液，方便地局部应用于创伤表面后，可以可靠和完全地防止术后粘连，正如在三个临床相关但越来越具有挑战性的大鼠模型中所证明的那样。整体完全预防成功率达93%以上，是防粘性能的重大飞跃。术后粘连是几乎所有类型的腹部和骨盆手术最常见的问题，导致不良后果。药物治疗和物理屏障装置是解决术后粘连的两种主要方法，但只能在一定程度上缓解或减少粘连。迫切需要一种可靠的方法来完全预防术后粘连并显著改善临床结果，然而，目前的技术还不能满足这一要求。在这里，我们报告了在三种临床相关但越来越具有挑战性的大鼠模型中，通过将粘稠的，乳状但可注射的两性离子聚合物溶液应用于创伤表面，完全可靠地防止了术后粘连。在42只实验动物中，完全预防的成功率超过93%，这是抗粘连性能的重大飞跃。临床上使用的Interceed膜几乎不能阻止这些模型的粘连。与目前仅作为物理屏障的抗粘附材料不同，“无污垢”两性离子聚合物作为抗粘附应用的保护层，具有抵抗蛋白质/细胞粘附的固有优势。聚合物的无污垢特性阻止了纤维连接蛋白和成纤维细胞的吸收，它们分别有助于粘连的初期和后期发展。这是将我们的“完全预防”方法与当前性能不佳的抗粘著材料区分开来的关键工作机制。这项工作提示了一种安全、有效、方便的方法来充分预防当前手术患者的术后粘连。
Significance Postoperative peritoneal adhesions are frequent complications for almost any types of abdominal and pelvic surgery and lead to numerous medical problems. Current antiadhesion solutions include pharmacological treatment and physical barriers but are underperformed and can only alleviate or reduce adhesions to some extent. Here we show that a zwitterionic polymer solution after a convenient topical application onto the traumatized surface can reliably and completely prevent the postoperative adhesions, as demonstrated in three clinically relevant but increasingly challenging rat models. The overall success rate of complete prevention is above 93%—a major leap of antiadhesion performance. Postoperative adhesions are most common issues for almost any types of abdominal and pelvic surgery, leading to adverse consequences. Pharmacological treatments and physical barrier devices are two main approaches to address postoperative adhesions but can only alleviate or reduce adhesions to some extent. There is an urgent need for a reliable approach to completely prevent postoperative adhesions and to significantly improve the clinical outcomes, which, however, is unmet with current technologies. Here we report that by applying a viscous, cream-like yet injectable zwitterionic polymer solution to the traumatized surface, postoperative adhesion was completely and reliably prevented in three clinically relevant but increasingly challenging models in rats. The success rate of full prevention is over 93% among 42 animals tested, which is a major leap in antiadhesion performance. Clinically used Interceed film can hardly prevent the adhesion in any of these models. Unlike current antiadhesion materials serving solely as physical barriers, the “nonfouling” zwitterionic polymer functioned as a protective layer for antiadhesion applications with the inherent benefit of resisting protein/cell adhesions. The nonfouling nature of the polymer prevented the absorption of fibronectins and fibroblasts, which contribute to the initial and late-stage development of the adhesion, respectively. This is the key working mechanism that differentiated our “complete prevention” approach from current underperforming antiadhesion materials. This work implies a safe, effective, and convenient way to fully prevent postoperative adhesions suffered by current surgical patients.