Borate ester-crosslinked polysaccharide hydrogel reinforced by proanthocyanidins for oral ulcer therapy

Oral ulcers are prone to recurrence and often complicated by bacterial infections. Currently, antibiotics, glucocorticoids, and anesthetics are commonly employed in clinical practice to alleviate symptoms. However, these medications exhibit limited retention in the moist and dynamic environment of the oral cavity, and their long-term use may lead to various side effects or drug resistance. In this study, we designed a borate ester cross-linked oxidation-responsive hydrogel (AHQP hydrogel) for the treatment of oral ulcers. The AHQP hydrogel is composed of phenylboronic acid-functionalized hyaluronic acid, sodium alginate, and quaternized chitosan (QCS), and is further enhanced by the incorporation of proanthocyanidins (PA) to strengthen its borate ester cross-linked network. These natural raw materials comprising the AHQP hydrogel exhibit excellent biocompatibility and degradability, ensuring that the hydrogel is safe for use in the oral cavity. Once the AHQP hydrogel adheres to the wet wound tissue, it degrades in response to reactive oxygen species, thereby releasing QCS and PA to exert therapeutic effects. Our results demonstrated that the AHQP hydrogel exhibits significant antioxidant, anti-inflammatory, antibacterial, and pro-angiogenic properties, thereby facilitating the healing of oral ulcers. Overall, this borate ester cross-linked polysaccharide hydrogel reinforced by PA presents promising prospects for the treatment of oral ulcers.