The objective of the present study was to study the impact of insulin insitu-gel formulation on healing progress after surgical procedures for treatment of dry tympanic membrane perforation for at least three consecutive months. At the beginning, an insulin insitu-gel was prepared from three different polymers compatible with insulin physiochemically and reported to be vain on insulin efficacy or safety. Insulin insitu-gel was prepared using chitosan, polyvinyl alcohol, and Pluronic F127 with glycerol as a penetration enhancer. Selection of an optimized formulation through in situ gel characterization and in vitro drug release kinetics then the formulation was evaluated for healing efficacy on human volunteers in RCT. A randomized controlled clinical study was implemented for clinical evaluation of insitu-gel formulation activity in the Department of Otorhinolaryngology, Minia University Hospital, from January 2025 to March 2026. Perforation healing signs as a primary indicator was followed and reported in three follow-up visits (1 week, 1 month, and 2 months) in addition hearing score pre- and post-surgery as secondary outcomes. Results of a clinical study showed that the healing is significantly superior in the insulin group than in the control group

Inclusion Criteria:

• aged 18 years or older,
• with a confirmed diagnosis of tubotympanic CSOM without discharge for at least three months,
• an intact ossicular chain, normal middle ear mucosa on otoscopic or endoscopic examination,
• conductive hearing loss indicated by an air-bone gap less than 30 dB

Exclusion Criteria:

• unfit for general anesthesia,
• had cervical spine disorders limiting operative positioning,
• active otorrhea, granulation tissue, or mucosal inflammation