Novel thermosensitive hydrogel for preventing formation of abdominal adhesions

Abstract

Xiang Gao,1,2 Xiaohui Deng,3 Xiawei Wei,2 Huashan Shi,2 Fengtian Wang,2 Tinghong Ye,2 Bin Shao,2 Wen Nie,2 Yuli Li,2 Min Luo,2 Changyang Gong,2 Ning Huang1 1Department of Pathophysiology, College of Preclinical and Forensic Medical Sciences, Sichuan University, Chengdu, 2State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, 3Department of Human Anatomy, Xinxiang Medical University, Xinxiang, People’s Republic of China Abstract: Adhesions can form after almost any type of abdominal surgery. Postoperative adhesions can be prevented by improved surgical techniques, such as reducing surgical trauma, preventing ischemia, and avoiding exposure of the peritoneal cavity to foreign materials. Although improved surgical techniques can potentially reduce formation of adhesions, they cannot be eliminated completely. Therefore, finding more effective methods to prevent postoperative adhesions is imperative. Recently, we found that a novel thermosensitive hydrogel, ie, poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCEC) had the potential to prevent postoperative adhesions. Using the ring-opening polymerization method, we prepared a PCEC copolymer which could be dissolved and assembled at 55°C into PCEC micelles with mean size of 25 nm. At body temperature, a solution containing PCEC micelles could convert into a hydrogel. The PCEC copolymer was biodegradable and had low toxicity in vitro and in vivo. We found that most animals in a hydrogel-treated group (n = 10) did not develop adhesions. In contrast, 10 untreated animals developed adhesions that could only be separated by sharp dissection (P < 0.001). The hydrogel could adhere to peritoneal wounds and degraded gradually over 7–9 days, transforming into a viscous fluid that was completely absorbed within 12 days. The injured parietal and visceral peritoneum remesothelialized over about seven and nine days, respectively. This study confirms that PCEC hydrogel has potential application in the prevention of postoperative adhesions. Keywords: poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone), thermosensitive, biodegradable, hydrogel, postoperative adhesions