Composition of Hyaluronan Affects Wound Healing in the Rabbit Maxillary Sinus

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Abstract
Background: Hyaluronan (HA) is a ubiquitous component of the extracellular matrix. HA and its derivatives have been used in the sinuses to reduce scarring and possibly promote wound healing. However, in recent animal studies, HA esters exhibited inflammatory effects. Mitomycin C (MMC) is another potential antiscarring treatment. This study prospectively evaluated the effects of three different HA constructs on wound healing in the rabbit maxillary sinus: (i) a novel cross-linked HA hydrogel, (ii) the cross-linked HA gel containing covalently bound MMC, and (iii) a commercially available woven HA ester (Merogel). Methods: Ostia were created with a 4-mm otologic drill in the maxillary sinuses of 15 New Zealand white rabbits with one side randomly chosen for treatment. After 14 or 21 days the size of the maxillary ostia were recorded and the tissue was examined under light microscopy. Results: Sinuses treated with the novel HA and HA-MMC hydrogels showed an increased ostial diameter compared with untreated controls. Woven HA ester–treated sinuses showed no improvement, with a trend toward a smaller ostium than controls. Histological examination showed that woven HA ester tended to cause increased fibrosis and granulomatous inflammation, and heterophilia was slightly increased in the HA hydrogel-treated sinuses. Blinded observation noted foamy macrophages surrounding the residual woven HA ester in each specimen while no similar reaction was noted near the residual HA or HA-MMC hydrogels. Conclusion: This study suggests that the degree of ostial narrowing, inflammation, and fibrosis depends on the formulation of the HA used. Minimal, if any, additional benefit is seen with addition of MMC to the HA hydrogel in this pilot study.