Hyaluronan and healing of tympanic membrane perforations. An experimental study

Hyaluronan, an extracellular high molecular weight polysaccharide, was applied onto experimentally performed tympanic membrane (TM) perforations in the rat. The hyaluronan-treated perforations closed faster than the untreated controls and showed less scar tissue. Initially the perforation became covered by a sheet of keratin and hyaluronan, which appeared to relax and orientate the retracted collagen fibres at the margin of the perforation. The hypertrophic stratified keratinizing squamous epithelium advanced within the hyaluronan-keratin cover and closed the perforation ahead of an approaching connective tissue. Three months after the closure, the hyaluronan-treated TMs appeared transparent in comparison to the opaque untreated controls. In histological sections the hyaluronan-treated TM was comparably thin and an organized collagen fibre layer was discernible. Hyaluronan of various concentrations (0.75, 1.0, 1.75 and 1.9%) and molecular weights (4 x 10(6) and 6 x 10(6)) were tested. The healing rate and degree of scar tissue was dependent on the concentration, but not on the molecular weight of the hyaluronan. Hyaluronan, at the higher concentration, healed the perforations faster and produced a less opaque TM than hyaluronan at low concentration. The number of applications of hyaluronan also influenced the healing rate; fewer applications resulted in a reduced rate. However, the quality of the healed TM was influenced to a lesser extent by the number of hyaluronan applications. Even single applications caused less scar tissue in comparison with untreated TMs. It is inferred from the study that hyaluronan, exogenously applied, might be valuable also in the clinical situation to enhance the healing of different types of TM perforation.