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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. 

The active pharmaceutical ingredients (APIs) have to cross the natural barriers and get into the blood to impart the pharmacological effects. The tight junctions (TJs) between the epithelial cells serve as the major selectively permeable barriers and control the paracellular transport of the majority of hydrophilic drugs, in particular, peptides and proteins. TJs perfectly balance the targeted transport and the exclusion of other unexpected pathogens under the normal conditions. Many biomaterials have shown the capability to open the TJs and improve the oral bioavailability and targeting efficacy of the APIs. Nevertheless, there is limited understanding of the biomaterial–TJ interactions. The opening of the TJs further poses the risk of autoimmune diseases and infections. This review article summarizes the most updated literature and presents insights into the TJ structure, the biomaterial–TJ interaction mechanism, the benefits and drawbacks of TJ disruption, and methods for evaluating such interactions.