Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI 48202.
Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI 48202
Proc Natl Acad Sci U S A. 2020 Dec 15;117(50):32046-32055. doi: 10.1073/pnas.2012491117. Epub 2020 Nov 30.
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.
术后粘连是几乎所有腹部和骨盆手术都面临的常见问题,会导致不良后果。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。目前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,但现有技术尚未满足这一需求。在这里,我们报告了一种粘性、乳膏状但可注射的两性离子聚合物溶液,将其应用于创伤表面,可以可靠地完全预防三种临床上相关但具有挑战性的大鼠模型中的术后粘连。在 42 只接受测试的动物中,完全预防的成功率超过 93%,这是防粘连性能的重大飞跃。临床上使用的 Interceed 膜在这些模型中几乎无法预防粘连。与目前仅作为物理屏障的防粘连材料不同,“抗污”两性离子聚合物作为一种防粘连的保护层,具有抵抗蛋白/细胞粘连的固有优势。聚合物的抗污性质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早期和晚期发展。这是我们的“完全预防”方法与现有表现不佳的防粘连材料的关键工作机制。这项工作为当前接受手术的患者提供了一种安全、有效、方便的完全预防术后粘连的方法。