Abstract

Acute liver injury (ALI) caused by acetaminophen (APAP) has a high incidence rate worldwide, and severe cases may cause liver failure or even death. N -acetylcysteine (NAC), as an effective treatment drug approved for clinical application in ALI, has limitations such as a short half-life and the requirement for high-dose injections. Consequently, it is imperative to optimize new administration method of NAC and promote alternative therapeutic strategies for ALI. Herein, hydrogel patches ONC composed of oxidized chondroitin sulfate (OCS) and NAC-grafted CMCS were developed, and their reparative effects on APAP-induced ALI were investigated. ONC hydrogels exhibited excellent biocompatibility and appropriate biodegradability, and favorable hemostatic effects in the liver. In vitro experiments demonstrated that ONC could promote the proliferation and migration of hepatocytes, as well as the angiogenesis of HUVECs. By establishing an APAP-induced ALI model in mice, liver enzymes after ONC hydrogel patches treatment recovered to near-normal levels. Moreover, histological examination, RT-qPCR, and transcriptome sequencing results demonstrated that ONC patches could reduce the expression of inflammatory factors and apoptosis in the liver, while simultaneously activating antioxidant-related signaling pathways, thereby promoting the regeneration and functional repair of damaged tissues. Therefore, ONC hydrogel patches may be a promising alternative strategy for treating ALI.