Challenges in functional hydrogel application for chronic tympanic membrane perforation: practical limitations and lessons learned

Gan-Erdene Narantsolmon; Yu-Jung Hwang; Min Ji Kim; Jin Young Hong; Soo Bin Yoon; Bayarmaa Enkhbat; Chang Hee Min; Myoung Ju Kim; Myung-Whan Suh; Young Bin Choy

doi:10.1007/s13534-025-00519-y

Challenges in functional hydrogel application for chronic tympanic membrane perforation: practical limitations and lessons learned

Biomed Eng Lett. 2025 Oct 29;16(1):153-165. doi: 10.1007/s13534-025-00519-y. eCollection 2026 Jan.

Authors

Gan-Erdene Narantsolmon^#^{1

2

3}, Yu-Jung Hwang^#¹, Min Ji Kim^#⁴, Jin Young Hong^#^{4

5}, Soo Bin Yoon^{4

5}, Bayarmaa Enkhbat³, Chang Hee Min⁶, Myoung Ju Kim^{4

5}, Myung-Whan Suh¹, Young Bin Choy^{4

5

7

6

8

9}

Affiliations

¹ Department of Otorhinolaryngology, Seoul National University Hospital, Seoul, 03080 Republic of Korea.
² Department of Otorhinolaryngology, First Central Hospital of Mongolia, Ulaanbaatar, 210648 Mongolia.
³ Department of Pathology and Forensic Medicine, Mongolian National University of Medical Science, Ulaanbaatar, 14210 Mongolia.
⁴ Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul, 08826 Republic of Korea.
⁵ Integrated Major in Innovative Medical Science, Seoul National University, Seoul, 03080 Republic of Korea.
⁶ Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul, 03080 Republic of Korea.
⁷ Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University, Seoul, 03080 Republic of Korea.
⁸ Innovative Medical Technology Research Institute, Seoul National University Hospital, Seoul, 03122 Republic of Korea.
⁹ ToBIOS Inc., 3F, 9-7 Seongbuk-ro 5-gil, Seongbuk-gu, Seoul, 02880 Republic of Korea.

^# Contributed equally.

Abstract

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.

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

Keywords: Biocompatibility; Hydrogel; In situ gelation; Manganese porphyrin; Transtympanic delivery; Tympanic membrane perforation.