Mangostanin hyaluronic acid hydrogel as an effective biocompatible alternative to chlorhexidine.

Periodontal disease (PD) prevention and treatment products typically demonstrate excellent antibacterial activity, but recent studies have raised concerns about their toxicity on oral tissues. Therefore, finding a biocompatible alternative that retains antimicrobial properties is imperative. In this study, a chemically modified hyaluronic acid (HA) hydrogel containing mangostanin (MGTN) was developed. Native HA was chemically modified, incorporating amino and aldehyde groups in different batches of HA, allowing spontaneous crosslinking and gelation when combined at room temperature. MGTN at different concentrations was incorporated before gelation. The structure, swelling characteristics MGTN release, rheological parameters, and in vitro degradation performance of the loaded hydrogel were first evaluated in the study. Then, antimicrobial properties were tested on Porphyromonas gingivalis and its biocompatibility in 3D-engineered human gingiva. HA hydrogel was very stable and showed a sustained release for MGTN for at least 7 days. MGTN-loaded HA hydrogel showed equivalent antimicrobial activity compared to a commercial gel of HA containing 0.2 % chlorhexidine (CHX). In contrast, while MGTN HA hydrogel was biocompatible, CHX gel showed high cytotoxicity, causing cell death and tissue damage. Modified HA hydrogel allows controlled release of MGTN, resulting in a highly biocompatible hydrogel with antibacterial properties. This hydrogel is a suitable alternative therapy to prevent and treat PD.