Physically Cross-Linked Hyaluronan-Based Ultrasoft Cryogel Prepared by Freeze–Thaw Technique as a Barrier for Prevention of Postoperative Adhesions

Postsurgical peritoneal adhesions are a common and serious postoperative complication after various peritoneal surgeries, such as pelvic and abdominal surgery. Various studies have shown that peritoneal adhesions can be minimized or prevented by physical anti-adhesion barriers, including membranes, knits, and hydrogels. Hydrogels have attracted great attention in preventing peritoneal adhesions because the dimensional architecture of hydrogels is similar to that of the native extracellular matrix. However, chemical cross-linkers had to be used in the preparation of chemical hydrogels, which may have problems in cytotoxicity or unwanted side effects. This fact prompts us to create alternative cross-linking methods for the development of biocompatible hydrogels as physical barriers. Herein, we report a physically cross-linked flexible hyaluronan (HA) cryogel prepared via a freeze–thaw technique as a novel anti-adhesion biomaterial for completely preventing postsurgical peritoneal adhesions. In vitro studies demonstrated that this physically cross-linked HA cryogel exhibited excellent biocompatibility, the inherently desirable biocompatibility and functionality of HA being integrally retained as much as possible. Intriguingly, the rheological properties and appropriate biodegradability of the cryogels were readily tailored and tunable by way of the gelation process. In vivo assessments suggested that the cryogel, as a physical barrier, satisfactorily prevented fibroblast penetration and attachment between the injured tissues and nearby normal organs. Furthermore, the molecular mechanism studies revealed that the HA cryogel could prevent peritoneal adhesion by inhibiting inflammatory response and modulation of the fibrinolytic system. Our results show that HA ultrasoft cryogel is a promising clinical candidate for prolonged adhesion prevention.