Emerging roles of hyaluronic acid bioscaffolds in tissue engineering and regenerative medicine

Hyaluronic acid (HA), is a glycosaminoglycan comprised of repeating disaccharide units of N-acetyl-d-glucosamine and d-glucuronic acid. HA is synthesized by hyaluronan synthases and reaches sizes in excess of 2 MDa. It plays numerous roles in normal tissues but also has been implicated in inflammatory processes, multiple drug resistance, angiogenesis, tumorigenesis, water homeostasis, and altered viscoelasticity of extracellular matrix. The physicochemical properties of HA including its solubility and the availability of reactive functional groups facilitate chemical modifications on HA, which makes it a biocompatible material for use in tissue regeneration. HA-based biomaterials and bioscaffolds do not trigger allergies or inflammation and are hydrophilic which make them popular as injectable dermal and soft tissue fillers. They are manufactured in different forms including hydrogels, tubes, sheets and meshes. Here, we review the pathophysiological and pharmacological properties and the clinical uses of native and modified HA. The review highlights the therapeutic applications of HA-based bioscaffolds in organ-specific tissue engineering and regenerative medicine.