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.