Poster O9 - Multifunctional Hydrogels for Postoperative Abdominal Adhesion Prevention

Introduction: Postoperative adhesions, as the most common adverse effect following abdominal surgical practice, lead to numerous severe clinical complications, including intestinal obstruction, chronic pain, female sterility, and even death. Current antiadhesive strategies focus mostly on physical barriers and are unsatisfactory and inefficient. In this study, we designed and synthesized advanced injectable hydrogels by the conjugation reaction of epigallocatechin gallate (EGCG) and hyaluronic acid (HA)-based microgels and polyvinyl alcohol (PVA) (HPE-PVA) based on the dynamic boronic ester bond. Furthermore, we fabricated multifunctional Janus hydrogels composing of polyethyleneimine/thioctic acid (PEI/TA) coacervate-derived hydrogel and HPE-PVA hydrogel for postoperative abdominal adhesion prevention.

Materials and

Methods: We first synthesized a phenylboronic acid (PBA)- EGCG complex and then generated an HA-PBA-EGCG (HPE) microgels by the copolymerization of HA and the PBA-EGCG complex (Figure 1A). Subsequently, the multifunctional hydrogels (HPE-PVA) were synthesized by mixing the HPE microgels with PVA through the formation of a boronic ester dynamic bond between boronic acid and 1,3-diol groups. We further explored the multiple functionalities of hydrogels, including rapid gelation, self-healing, anti-oxidation, anti-inflammation, and anti-cellular adhesion in vitro. We have developed a mouse cecum–abdominal wall adhesion model by gently abrading the cecum and injuring abdominal wall.

Results, Conclusions, and Discussions: As shown in Figure 1B, scanning electron microscope (SEM) images showed that the cream-like hydrogels (HPE-PVA) containing 2 wt % HPE microgel and 1 wt% PVA exhibited porous microstructures with microgel particles. Meanwhile, the hydrogel with self-healing properties was confirmed to be injectable through insulin needles (29 G). HPE-PVA hydrogels had no significant cytotoxicity on fibroblasts (Figure 1C) and exhibited promising anti-inflammatory and antioxidative properties by downregulating pro-inflammatory gene expressions (TNFA, NFKB, Figure 1D) and cytokine secretions (TNF-α, IL-1β, Figure 1E), and reducing intracellular reactive oxygen species (ROS, Figure 1F and Figure 1G). In addition, we developed a mouse cecum- abdominal wall (AW) adhesion model to evaluate the ability of our hydrogels to prevent postoperative cecum-abdominal adhesions, with comparisons to commercial Seprafilm and untreated mice (Figure 1H). As shown in Figure 1I, the cecum-abdominal adhesion formation was performed by reopening the abdomen after 2 weeks post-surgery. Masson’s trichrome images also showed that the Injury-only group showed severe adhesions between the AW and cecum (The black arrows pointed to adhesion sites).
In summary, we designed and synthesized injectable cream-like hydrogels by the conjugation reaction of HPE microgels and PVA based on the dynamic boronic ester bond, which had multiple functionalities, including rapid gelation, self-healing, anti-oxidation, anti-inflammation, and anti-cellular adhesion. As shown in Figure 1H, we will further fabricate asymmetric Janus hydrogels with highly wet tissue adhesion (PEI-TA hydrogel) and antiadhesion (HPE-PVA hydrogel) properties for postoperative abdominal adhesion prevention in vivo, simultaneously with tough mechanical strength and facile preparation.

Acknowledgements (Optional): Scientist Development Award (Department of Internal Medicine, University of Nebraska Medical Center); University of Nebraska Collaboration Initiative Grant; Great Plains IDeA-CTR Network.