Evaluation of in vivo biocompatibility and biodegradation of photocrosslinked hyaluronate hydrogels (HADgels)

Abstract
HADgels are newly developed photocrosslinked hyaluronate hydrogels. They are produced from an aqueous solution of a hyaluronan derivative (HAD) in which cinnamic acid is introduced into the carboxyl moiety of hyaluronan using 3-aminopropanol as a spacer. High-energy ultraviolet irradiation of the HAD solution induces photodimerization of cinnamic acid, resulting in the development of a macromolecular network of each hyaluronan to water-insoluble hydrogels. The biocompatibility and biodegradation of HADgels were evaluated by guinea pig intracutaneous injection testing for up to 28 days. By macroscopic and histological observations, HADgels showed good tissue compatibility and did not induce excess inflammation at the injection sites. Biodegradation of the HADgels clearly depended on the degree of crosslinking at the fixed weight concentrations of HAD (0.5% and 1.0%). In addition, serum analyses showed that the injected guinea pigs did not produce specific antibodies against HADgels. These results indicate that HADgels have preferable biocompatibility and can be used as a new class of injectable, absorbable biomaterial, especially for preventing postsurgical adhesion formations.