Fouling-resistant zwitterionic polymers for complete prevention of postoperative adhesion

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 117; no. 50; pp. 32046 - 32055
• Main Authors: Zhang, Ershuai, Song, Boyi, Shi, Yuanjie, Zhu, Hui, Han, Xiangfei, Du, Hong, Yang, Chengbiao, Cao, Zhiqiang
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 15.12.2020
• Subjects: Acrylamides - administration & dosage; Adhesion; Animal models; Animals; Barriers; Biological Sciences; Disease Models, Animal; Drug therapy; Fibroblasts; Humans; Intraoperative Care - methods; Peritoneal Diseases - etiology; Peritoneal Diseases - prevention & control; Physical Sciences; Polymers; Polymers - administration & dosage; Postoperative Complications - etiology; Postoperative Complications - prevention & control; Prevention; Rats; Solutions; Surgery; Surgical Procedures, Operative - adverse effects; Test animals; Tissue Adhesions - etiology; Tissue Adhesions - prevention & control; Zwitterions; hepatectomy; adhesiolysis; postoperative adhesion; antiadhesion; zwitterionic polymer
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2012491117

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.