Structural Variations in a Single Hyaluronan Derivative Significantly Alter Wound‐Healing Effects in the Rabbit Maxillary Sinus

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Abstract
Background: Biomaterials based on hyaluronan (HA) are currently used after sinus surgery but have not been found to decrease scarring or enhance wound healing. Chemical composition of these modified HA molecules may impact their biological and clinical effects.Objective: To analyze chemical variations of a single crosslinked HA‐based hydrogel, chemically modified thiolated HA (CMHA‐SX).Methods: Four different components of the hydrogel composition were altered, yielding 54 variations. These were subjected to biomechanical testing, and then potential clinically relevant variations were further tested for swelling and degradation characteristics. Using a rabbit maxillary sinus model, the ability of the material variations to stent a neo‐ostium was tested. Histologic measures were also assessed. Biomechanical and biological effects were correlated.Results: Minor compositional changes had profound biomechanical and biological effects. Swelling and rate of enzymatic degradation were closely related. CMHA‐SX hydrogels that were the most effective stents in maintaining the neo‐ostium also generated the lowest level of acute inflammation, as determined by histology.Conclusions: Chemical composition has a significant impact on the clinical potential of modified HA materials. Histocompatibility appears to most significantly affect ostium preservation.Significance: Different CMHA‐SX hydrogels perform differently in vivo, even when the chemical compositions are quite similar. Objective prospective testing of modified HA materials should precede their clinical use in sinus surgery.