Dual dynamically crosslinked thermosensitive hydrogel with self-fixing as a postoperative anti-adhesion barrier

Abstract

Tissue adhesion is a severe postoperative complication. Various strategies have been developed to minimize postoperative adhesion, but the clinical efficacy is still far from satisfactory. Herein, we present a dual dynamically crosslinked hydrogel to serve as a physical postoperative anti-adhesion barrier. The hydrogel was generated by dynamic chemical oxime bonding from alkoxyamine-terminated Pluronic F127 (AOP127) and oxidized hyaluronic acid (OHA), as well as hydrophobic association of AOP127. Rheological analysis demonstrated that the hydrogel exhibits temperature sensitivity. At 37 °C, it shows much higher modulus and higher stability than the Pluronic F127 hydrogel. Hemolytic assays suggested that the hydrogel undergoes low hemolysis. In addition, it exhibited anti-adhesion to blood cells in blood cell adhesion tests. It also showed an anti-attachment effect to fibroblasts and biocompatibility in vitro cell studies. Macroscopic evaluation and lap-shear tests revealed that the hydrogel has a moderate adhesive capacity to tissue, which is important for self-fixation. A rat model of sidewall defect-bowel abrasion was established to evaluate the anti-adhesion effect in vivo. The gross observation and pathological analysis revealed a significant reduction in postoperative peritoneal adhesion in the AOP127/OHA hydrogel-treated group than those treated with normal saline or Pluronic F127 hydrogel. Hence, the dual dynamically crosslinked hydrogel with self-fixable capacity may be suitable as a physical barrier for postoperative adhesion prevention. Statement of SignificanceDespite the development of numerous postoperative anti-adhesion barriers, their anti-adhesion efficacy is still limited in clinical trials due to poor tissue adhesion and rapid clearance from injured areas. Herein, we have developed a dual dynamic crosslinked hydrogel, generated by dynamic oxime bonds and hydrophobic interactions. The hydrogel is temperature-sensitive and demonstrates moderate tissue adhesion capacity, which allows for self-fixation when applied to defects. The introduction of dynamic covalent bonds improves the stability of the hydrogel. Moreover, the hydrogel not only displays appropriate hemocompatibility, cytocompatibility and anti-adhesion of blood cells and fibroblasts, but it also effectively contributes to preventing postoperative peritoneal adhesions in vivo. Hence, this dual dynamic crosslinked hydrogel may have potential applications as a physical barrier in clinical practice.