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Abstract Postoperative peritoneal adhesions are frequent complications for almost any type of abdominal and pelvic surgery. This leads to numerous medical problems and a huge financial burden to the patients. Current anti‐adhesion strategies focus mostly on physical barriers including films and hydrogels. However, they can only alleviate or reduce adhesions to a certain level and their applying processes are far from ideal. This work reported the development of a biodegradable zwitterionic cream gel presenting a series of characters for an ideal anti‐adhesion material, including unique injectable yet malleable and self‐supporting properties, which enables an instant topical application, no curing, waiting, or suturing, no hemostasis requirement, protein/cell resistance, and biodegradability. The cream gel shows a major advancement in anti‐adhesion efficacy by completely and reliably preventing a primary and more severe recurrent adhesion in rat models. 

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.