Methods for determining the structure and physicochemical properties of hyaluronic acid and its derivatives: A review

Hyaluronic acid (HA) is a linear high molecular weight polymer ubiquitously distributed in humans and animals. The D-glucuronic acid and N-acetyl-D-glucosamine repeating disaccharide backbone along with variable secondary and tertiary structures endows HA with unique rheological characteristics as well as diverse biological functions such as maintaining tissue homeostasis and mediating cell functions. Due to its excellent biocompatibility, biodegradability, viscoelasticity and moisturizing properties, natural HA and its chemically modified derivatives are widely used in medical, pharmaceutical, food and cosmetic industries. For broad application purposes, abundant HA-based biochemical products have been developed, including the methodologies for characterization of these products. This review provides an overview focusing on the methods used for determining HA structure as well as the strategies for constructing its derivatives. Apart from the analytical approaches for defining the physicochemical properties of HA (e.g., molecular weight, rheology and swelling capacity), quantitative methods for assessing the purity of HA-based materials are discussed. In addition, the biological functions and potential applications of HA and its derivatives are briefly embarked and perspectives in methodological development are discussed.