Hyaluronic acid-based composite hydrogels embedded with core-shell microgels with properties of mucosal adhesion and combined drug administration for chemoradiotherapy induced oral mucositis.

Chemoradiotherapy-induced oral mucositis (CIOM), characterized by high incidence and delayed healing, severely impairs patient recovery and quality of life. Current treatments face challenges due to poor wet adhesion, dynamic oral environments, and lack of multiple active substances for mucosal repair. This situation makes an urgent need for therapeutic platforms that combine robust mucosal adhesion with multifunctionality. In this study, a crosslinked hyaluronic acid based hydrogel (PHB) embedded with core-shell microgels was developed. Core-shell microgels were fabricated to encapsulate growth factor (core) and lidocaine (shell), enabling spatiotemporal drug release. The hydrogel exhibited superior mucosal adhesion, with a displacement of only 5.5 mm after 24 h on an inclined agar plate containing mucin, attributed to hydrogen bonding between hydroxyl groups of PHB and mucin. The bacteriostasis experiment results show that PHB has excellent antibacterial properties against E. coli and S. aureus, which can help to prevent the growth of oral bacteria and promote wound healing. Furthermore, sustained release of EGF and lidocaine from the PHB hydrogel was maintained for 24 h, aligning with the time window required for oral mucosal repair. In vivo studies demonstrated PHB hydrogels accelerated mucosal proliferation and remodeling in CIOM in golden hamsters. This study presents a combined drug hydrogel system addressing CIOM's multifactorial pathology. The PHB platform synergizes prolonged wet adhesion, antibacterial action, analgesia, and tissue regeneration, offering a clinically solution for oral mucosal repair.