Dual-functional injectable hydrogels as antimicrobial and angiogenic therapeutics for dental pulp regeneration†

Abstract

Pulpitis is a painful inflammatory condition of the dental pulp, commonly triggered by bacterial infection, trauma, or repeated dental procedures. Patients often experience heightened sensitivity to temperature changes, spontaneous pain, and, in severe cases, necrosis of the pulp tissue, leading to tooth loss if left untreated. Traditional treatment primarily involves root canal therapy, which removes infected pulp and seals the canal with gutta-percha; however, this approach lacks antimicrobial properties and does not support tissue regeneration. To address these limitations, this study investigates an injectable hydrogel system composed of hyaluronic acid (HA) and carboxymethyl chitosan (CMCs), chemically crosslinked with 1,4-butanediol diglycidyl ether (BDDE). The hydrogel demonstrated excellent injectability, self-healing ability, and mechanical stability. In vitro and in vivo assessments confirmed its biocompatibility, biodegradability, and capability for controlled release of therapeutic agents. Notably, the amoxicillin-loaded hydrogel (HACM/AX) showed significant antibacterial properties; while the erythropoietin-loaded hydrogel (HACM/EPO) significantly enhanced endothelial cell proliferation and migration, facilitating angiogenesis for tissue regeneration. These findings highlight the potential of the HACM hydrogel as a dual-function biomaterial with antimicrobial and pro-angiogenic properties, offering a promising alternative for pulpitis treatment and dental tissue engineering.