Abstract
Since its first isolation in 1934, hyaluronic acid (HA) has been studied across a variety of research areas. This unbranched glycosaminoglycan consisting of repeating disaccharide units of N-acetyl-d-glucosamine and d-glucuronic acid is almost ubiquitous in humans and in other vertebrates. HA is involved in many key processes, including cell signaling, wound reparation, tissue regeneration, morphogenesis, matrix organization and pathobiology, and has unique physico-chemical properties, such as biocompatibility, biodegradability, mucoadhesivity, hygroscopicity and viscoelasticity. For these reasons, exogenous HA has been investigated as a drug delivery system and treatment in cancer, ophthalmology, arthrology, pneumology, rhinology, urology, aesthetic medicine and cosmetics. To improve and customize its properties and applications, HA can be subjected to chemical modifications: conjugation and crosslinking. The present review gives an overview regarding HA, describing its history, physico-chemical, structural and hydrodynamic properties and biology (occurrence, biosynthesis (by hyaluronan synthases), degradation (by hyaluronidases and oxidative stress), roles, mechanisms of action and receptors). Furthermore, both conventional and recently emerging methods developed for the industrial production of HA and its chemical derivatization are presented. Finally, the medical, pharmaceutical and cosmetic applications of HA and its derivatives are reviewed, reporting examples of HA-based products that currently are on the market or are undergoing further investigations.
Highlights
Introduction and Historical Background of HAResearch on hyaluronic acid (HA) has expanded over more than one century.The first study that can be referred to regarding HA dates from 1880: the French scientist Portes observed that mucin from vitreous body was different from other mucoids in cornea and cartilage and called it “hyalomucine” [1]
HA is synthesized as a free linear polymer by three transmembrane glycosyltransferase isoenzymes named hyaluronan synthases, HAS: HAS1, HAS2 and HAS3, whose catalytic sites are located on the inner face of the plasma membrane
Despite the extraction protocols being improved over the years, this methodology was always hampered by several technical limitations, which led to the production of highly polydispersed HA (MW ≥ 106 Da) with a low yield [1,46]
Summary
Research on hyaluronic acid (HA) has expanded over more than one century. The first study that can be referred to regarding HA dates from 1880: the French scientist Portes observed that mucin from vitreous body was different from other mucoids in cornea and cartilage and called it “hyalomucine” [1]. HA represents a key molecule in a variety of medical, pharmaceutical, nutritional and cosmetic applications For this reason, HA is still widely studied to elucidate its biosynthetic pathways and molecular biology, to optimize its biotechnological production, to synthesize derivatives with improved properties and to optimize and implement its therapeutic and aesthetic uses [1,42,43,44,46,47,48,49,50,51,52,53,54,55,56,57,58]. With the aim to give a clearer picture about where researches and applications in the field are going, the present work starts with an update of HA’s physico-chemical, structural and hydrodynamic properties and proceeds with the discussion of HA biology: occurrence, biosynthesis (by hyaluronan synthases), degradation (by hyaluronidases and oxidative stress), roles, mechanisms of action and receptors Both conventional and recently-emerging methods developed for the industrial production of HA and its chemical derivatization are described. Many physiological roles and pharmaceutical, medical, food and cosmetic applications of hyaluronan
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