Preparation and characterization of a novel composite acellular matrix/hyaluronic acid thermosensitive hydrogel for interstitial cystitis/bladder pain syndrome

Bladder mucosa damage that causes harm to the interstitium is a recognized pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS). The intravesical instillation of drugs is an important second-line therapy, but it is often necessary to use drugs repeatedly in the clinic because of their short residence time in the bladder cavity, which alters the therapeutic effect. To overcome this drawback, this study developed a novel composite acellular matrix/hyaluronic acid (HA) thermosensitive hydrogel (HA-Gel) using rabbit small intestinal submucosa extracellular matrix (ECM) as the thermosensitive material and HA as the drug component and examined its composition, microstructure, thermodynamic properties, temperature sensitivity, rheological properties, biocompatibility, drug release, hydrogel residue, and bacteriostatic properties. The study showed HA-Gel was liquid at temperatures of 15-37.5°C and solid at 37.5-50°C, its swelling rate decreased with increasing temperature, and its lower critical solution temperature occurred at approximately 37.5°C. This property made the hydrogel liquid at room temperature convenient for intravesical perfusion and turned into a solid about 1 min after entering the body and rising to body temperature to increase its residence time. Subsequent experiments also proved that the gel residue time of HA-Gel in vivo and the drug release time of HA in vivo could reach more than 5 days, which was significantly higher than that of HA alone, and it had good biocompatibility and antibacterial properties. Therefore, this hydrogel possesses the proper characteristics to possibly make it an ideal dosage form for IC/BPS intravesical instillation therapy.