Multifunctional microgel-based cream hydrogels for postoperative abdominal adhesion prevention

Authors

• Bo Liu, University of Nebraska Medical CenterFollow
• Yunfan Kong, University of Nebraska Medical Center
• Olawale A. Alimi, University of Nebraska Medical Center
• Mitchell Kuss, University of Nebraska Medical CenterFollow
• Huiyin Tu, University of Nebraska Medical CenterFollow
• Wenfeng Hu, University of Nebraska Medical Center
• Abu Rafay, University of Nebraska Medical Center
• Kumar Vikas, University of Nebraska Medical Center
• Wen Shi, University of Nebraska Medical Center
• Megan Lerner, University of Oklahoma Health Sciences Center
• William L. Berry, University of Oklahoma Health Sciences Center
• Yulong Li, University of Nebraska Medical CenterFollow
• Mark A. Carlson, University of Nebraska Medical Center, OmahaFollow
• Bin Duan, University of Nebraska Medical CenterFollow

Document Type

Article

Date of this Version

2-28-2023

Citation

ACS Nano. 2023 February 28; 17(4): 3847–3864. doi:10.1021/acsnano.2c12104.

Comments

HHS Public Access.

Abstract

Postoperative abdominal adhesions are a common problem after surgery and can produce serious complications. Current anti-adhesive strategies focus mostly on physical barriers and are unsatisfactory and inefficient. In this study, we designed and synthesized advanced injectable cream-like hydrogels with multiple functionalities, including rapid gelation, self-healing, anti-oxidation, anti-inflammation, and anti-cellular adhesion. The multifunctional hydrogels were facilely formed by the conjugation reaction of epigallocatechin gallate (EGCG) and hyaluronic acid (HA)-based microgels and polyvinyl alcohol (PVA) based on the dynamic boronic ester bond. The physicochemical properties of the hydrogels including anti-oxidative and anti-inflammatory activities were systematically characterized. A mouse cecum-abdominal wall adhesion model was implemented to investigate the efficacy of our microgel-based hydrogels in preventing postoperative abdominal adhesions. The hydrogels, with a high molecular weight HA, significantly decreased the inflammation, oxidative stress, and fibrosis, and reduced the abdominal adhesion formation, compared to the commercial Seprafilm group or Injury-only group. Label-free quantitative proteomics analysis demonstrated that S100A8 and S100A9 expressions were associated with adhesion formation; the microgel-containing hydrogels inhibited these expressions. The microgel-containing hydrogels with multifunctionality decreased formation of postoperative intraabdominal adhesions in a murine model, demonstrating promise for clinical applications.