ROS-responsive caffeic acid phenethyl ester-conjugated carboxymethyl chitosan hydrogel for treatment of periodontitis

Periodontitis , an inflammatory disease caused by bacterial infection, is characterized by an abundance of reactive oxygen species (ROS) in the affected area. These ROS induce oxidative stress, which leads to periodontal tissue damage . This study develops a novel prodrug , CCBC hydrogel, which delivers both anti-inflammatory benefits and ROS scavenging capabilities. The CCBC hydrogel covalently bonds biocompatible carboxymethyl chitosan (CC) with caffeic acid phenethyl ester (CAPE) through an aryl borate linkage. In vitro release experiments revealed that CCBC hydrogel rapidly releases CAPE in environments with high levels of ROS. Additionally, the CCBC hydrogel significantly reduced the expression of inflammatory factors such as TNF-α, IL-6, IL-17, and IL-1β, and effectively prevented apoptosis in PDLSCs by lowering ROS levels. Our study advances the targeted inflammatory delivery of the active monodrug CAPE, effectively clearing excess ROS and ameliorating the inflammatory microenvironment. Therefore, we believe that CCBC hydrogels hold significant potential for the treatment of periodontitis. Mechanism diagram of CCBC hydrogel. In an environment with high levels of ROS, the borate bond of CCBC is broken and CAPE is released. CAPE can inhibit the inflammatory response and ROS levels in PDLSCs by activating the Nrf2/HO-1 pathway. Furthermore, CAPE inhibited the production of caspase3/Bax/Bcl-2 pathway-mediated apoptosis within PDLSCs.