In vivo biocompatibility and biodegradability of bilayer films based on hyaluronic acid and chitosan for ENT surgery

Nasal septal perforations are now a frequent pathology, occurring in 2% of the population. They are caused by a number of factors: uncontrolled use of topical drugs for nasal breathing recovery, synthetic steroids, long rehabilitation period after septal surgery, nasal trauma with massive cartilage destruction.

Conversely, persistent tympanic membrane defects could be caused by the long-term inflammatory processes (e.g. chronic otopyosis), and trauma.

These defects cannot be restored even with modern reconstructive microsurgery due to the lack of suitable material for making prostheses able to provide both volumetric reparation processes of functional character - restoration of cartilage, mucosa and delicate connective tissue matrix for these organs while replacing the significant areas of the lost organ elements.

The aim of this study is to evaluate the in vivo biocompatibility and biocompatibility of bilayer cast films based on hyaluronic acid with molecular weight equal to 1300 kDa and chitosan with molecular weights equal to 500 and 900 kDa with potential use as devices for surgical reconstruction of acute posttraumatic defects of the tympanic membrane and septal cartilage. For the in vivo assay 20 Wistar rats (weight 220-240 g) were used. Total toxicity, pro-inflammatory activity, biodegradation rate and proliferative potential of the connective tissue of the dermis in the implantation area were evaluated on days 7, 14, 30, 50 after implantation. All studied materials were demonstrated to have low overall acute and chronic toxicity. The analysis of influence of the manufacturing technique, e.g. temperature treatment 100°Cx5 min, as well as chitosan molecular weight on the bioresorption intensity is demonstrated. It could be concluded, that the temperature treatment has higher influence of biodegradation period in comparison with the chitosan molecular weight and allows obtaining films with tunable biodegradability. After the additional analysis these bilayer films could be recommended for the ENT surgery, in particular, for the reconstruction of nasal septum and tympanic membrane.