Comprehensive review on biosynthesis of hyaluronic acid with different molecular weights and its biomedical applications

Hyaluronic acid (HA), an anionic and nonsulfated glycosaminoglycan, is the main structural component of various tissues and plays an important role in various biological processes. Given the promising properties of HA, such as high cellular compatibility, moisture retention, antiaging, proper interaction with cells, and CD44 targeting, HA can be widely used extensively in drug delivery, tissue engineering, wound healing, and cancer therapy. HA can obtain from animal tissues and microbial fermentation, but its applications depend on its molecular weight. Microbial fermentation is a common method for HA production on an industrial scale and S. zooepidemicus is the most frequently used strain in HA production. Culture conditions including pH, temperature, agitation rate, aeration speed, shear stress, dissolved oxygen, and bioreactor type significantly affect HA biosynthesis properties. In this review all the HA production methods and purification techniques to improve its physicochemical and biological properties for various biomedical applications are discussed in details. In addition, we showed that how HA molecular weight can significantly affect its properties and applications.