Desafíos en la aplicación de hidrogeles funcionales para la perforación crónica de la membrana timpánica:...

Chronic tympanic membrane (TM) perforations often persist due to oxidative stress and hypoxia in the middle ear. A minimally invasive, biocompatible hydrogel addressing these challenges could serve as an effective therapeutic dressing. A thiolated chitosan (CS-SH) and manganese porphyrin (MnP)-conjugated polyethylene glycol maleimide (MnP-PEG-MAL) hydrogel (Ch_MnP) was developed through in situ gelation via Michael addition reaction. Its mechanical properties and antioxidant activities (SOD- and CAT-like), were evaluated in vitro. For in vivo testing, Ch_MnP hydrogel was transtympanically injected into a chronic TM perforation rat model. Efficacy and safety were assessed using endoscopy, 3D computed tomography (CT), auditory brainstem response (ABR) testing, and histological analysis. The hydrogel exhibited optimal porosity and a swelling ratio of ~ 155%, making it well-suited as a wound healing scaffold. MnP incorporation enhanced reactive oxygen species (ROS) scavenging and O₂ generation under oxidative conditions. However, in vivo application showed no apparent improvement in TM regeneration, ABR thresholds, or histological outcomes. CT revealed a substantial hydrogel volume loss over 3 weeks, indicating significant water loss. This dehydration compromised the hydrogel's structural integrity and functionality, diminishing its role as a scaffold and therapeutic agent. The Ch_MnP hydrogel exhibited excellent biocompatibility and antioxidant properties, with potential to alleviate chronic inflammation in TM perforation. However, healing of the perforation was not observed during the study period, primarily due to dehydration in the dry middle ear. These findings underscore the importance of maintaining a hydrated environment to enhance the therapeutic efficacy of hydrogel-based TM perforation treatments.

The online version contains supplementary material available at 10.1007/s13534-025-00519-y.