A versatile hydrogel with sequential drug-releasing capability for the programmable healing of suppurative otitis media

Suppurative otitis media (SOM) is a condition characterized by the invasion of pathogenic bacteria into the middle ear via the eustachian tube (ET) or tympanic membrane (TM), significantly impacting the health of patients. Ear drops are frequently employed in clinical practice. Still, their efficacy is limited by their inability to penetrate the TM and their susceptibility to clearance through the ET, which does not address the comprehensive treatment needs. In this study, a novel injectable hydrogel (HGCCB hydrogel) is fabricated by the radical copolymerization and dynamic covalent bonding using chlorogenic acid-grafted methacrylate hyaluronic acid (HA-GCGA) and phenylboronic acid-modified ciprofloxacin (Cip-PBA) without any chemical crosslinkers. HGCCB hydrogel demonstrates favorable injectability, significant antibacterial activity, and anti-inflammatory properties. Importantly, dynamic boronate ester bonds within the HGCCB hydrogel facilitate the rapid release of Cip-PBA upon injection into the tympanic cavity, effectively targeting bacterial pathogens. Meanwhile, HA-GCGA acts as a prodrug, enabling the sustained release of chlorogenic acid through ester bond hydrolysis, thereby achieving a sequential drug release profile. Furthermore, the intratympanic injection of HGCCB hydrogel successfully treated SOM in a rat model, mitigating bacterial infection and inflammatory responses in the middle ear. This functional hydrogel presents a straightforward and effective strategy for treating SOM.