Outstanding Degradation Resistance of Hyaluronic Acid Achieved by Flavonoid Conjugations: Rheological Behavior

The functional conjugations with natural polyphenols could be a working strategy for accomplishing the degradation resistance of hyaluronic acids (HA). Herein, a series of HA conjugates with four different polyphenols with wide ranges in the degree of substitution were systematically prepared. The degradation rate could be retarded in a wide range without crosslinking: The conjugates having polyphenolic aglycone (catechin or quercetin) maintained their structures, as identified by viscosity, for up to 7 weeks in the presence of hyaluronidase. This retardation was outstanding compared to those reported from previous studies, and the physical mixtures of HA and polyphenols still showed significantly more retarded degradation than pristine HA. The degradation resistance could be controlled by varying the feed ratio of polyphenols. This conjugation method of polyphenols could open up new application areas of HA with the outstanding degradation resistance.