Bioinspired Injectable Thermosensitive Gallic Acid-Conjugated Hyaluronic Acid/Pluronic Hydrogels to Prevent Postoperative Adhesion

Abstract

Abstract

Postsurgical adhesions are common complications of abdominal and pelvic surgeries, often leading to bowel obstruction, chronic pain, and increased risks during reoperation. Although various physical barrier materials have been developed to prevent postsurgical adhesions, retaining anti-adhesive materials at surgical sites is challenging. In this study, we developed thermosensitive injectable gallic acid-conjugated hyaluronic acid (HA-GA) and Pluronic F127 (PluF) composite hydrogels to retain anti-adhesive materials and prevent postsurgical adhesion. The incorporation of HA-GA reduced the critical gelation concentration of PluF from approximately 18 to 12 wt% and decreased the gelation temperature from 28.5 °C for PluF to 25.6 °C for HA-GA (2 wt%)/PluF hydrogels with the left-shift in sol–gel curves. The G′ values increased from 10.1 ± 1.7 kPa for PluF to 24.8 ± 3.6 kPa for HA-GA (2 wt%)/PluF hydrogels at 37 °C. In addition, the HA-GA/PluF hydrogels exhibited enhanced mass retention as a function of time compared to PluF hydrogels alone. HA-GA (2 wt%)/PluF hydrogels retained 33.4 ± 3.5% of their initial mass after 7 d, whereas PluF was completely eroded within 3 d. The anti-adhesion efficacy of the HA-GA/PluF hydrogels was evaluated using a rat cecum abrasion model. Notably, the HA-GA (2 wt%)/PluF hydrogels showed reduced adhesion scores, with an adhesion extent score of 0.67 and 2.33 on postoperative day 7 and 21, respectively, compared with the untreated control group (3 and 3 on postoperative day 7 and 21). In addition, the adhesion severity scores of HA-GA (2 wt%)/PluF hydrogel groups were 0.33 and 1.33 on postoperative day 7 and 21, respectively, compared with the untreated control groups (1.67 and 2.33 on postoperative day 7 and 21). Therefore, HA-GA/PluF hydrogels provide reversible thermosensitive properties with enhanced stability and retention, supporting their potential as injectable physical barriers for postoperative adhesion prevention.