Hyaluronan: From Biomimetic to Industrial Business Strategy

Abstract

Hyaluronan (hyaluronic acid) is a naturally occurring polysaccharide of a linear repeating disaccharide unit consisting of β-(1→4)-linked D-glucopyranuronic acid and β-(1→3)-linked 2-acetamido-2-deoxy-D-glucopyranose, which is present in extracellular matrices, the synovial fluid of joints, and scaffolding that comprises cartilage. In its mechanism of synthesis, its size, and its physico-chemical properties, hyaluronan is unique amongst other glycosaminoglycans. The network-forming, viscoelastic and its charge characteristics are important to many biochemical properties of living tissues. It is an important pericellular and cell surface constituent; its interaction with other macromolecules such as proteins, participates in regulating cell behavior during numerous morphogenic, restorative, and pathological processes in the body. The knowledge of HA in diseases such as various forms of cancers, arthritis and osteoporosis has led to new impetus in research and development in the preparation of biomaterials for surgical implants and drug conjugates for targeted delivery. A concise and focused review on hyaluronan is timely. This review will cover the following important aspects of hyaluronan: (i) biological functions and synthesis in nature; (ii) current industrial production and potential biosynthetic processes of hyaluronan; (iii) chemical modifications of hyaluronan leading to products of commercial significance; and (iv) and the global market position and manufacturers of hyaluronan.

Articular Joint Lubricants during Osteoarthritis and Rheumatoid Arthritis Display Altered Levels and Molecular Species

“…This glycosaminoglycan has a high molecular weight (MW) distribution in human SF, ranging from 27 kDa to 10 MDa [ 12 – 14 ]. HA forms long nonsulfated chains of repeating disaccharides, comprising D-glucuronic acid and N-acetyl D-glucosamine, and provides SF with its high viscosity [ 9 – 12 , 15 , 16 ].…”

Versatile Use of Chitosan and Hyaluronan in Medicine

“…The average 70 kg adult human body contains approximately 15 g of HA, of which one third is turned over every day [ 24 ]. This biopolymer is really outstanding among the natural hygroscopic (macro)molecules; during the process of water absorbance, high-molar-mass HA molecules swell in volume up to 1000 times in the form of polymer powder [ 24 , 25 , 26 , 27 ]. The biological effects of HA depend on their molar masses.…”

“…Hyaluronan-derived products have been used to maintain the structure of the eye’s capsule, mainly in the phacoemulsification (removal of the eye’s vitreous humor) step of cataract surgery, but also in other surgical procedures such as corneal transplantation, intraocular lens implantation, and vitreoretinal, anterior segment, and glaucoma surgery. Some biocompatible materials were introduced in the ophthalmic practice for the vitreous humor replacement after vitrectomy using a new crosslinked HA through adipic acid dihydrazide bridges [ 25 ]. It has been demonstrated that treatment with eye drops containing HA reduces oxidative stress in the conjunctiva of patients with dry eye disease [ 49 , 50 ].…”

“…Some HA-based materials are commercially available for the treatment of deep dermal lesions such as non-healing ulcers, deep II and III degree burns (Hyalograft TM 3D), for autologous skin replacement (Laserskin ® ), for autologous fibroblasts, and for keratinocyte replacement (Tissuetech ® ). Other commercially available HA-based products on the market are Hyalofill-f ® , Hyalofill-R ® , Connettivina ® , Connettivina Plus ® , Jaloskin ® , and Hyalomatrix ® [ 25 ]. Hyiodine ® (Contipro) is a patented complex of 1.5% sodium hyaluronate, produced through a process of bacterial fermentation, which was developed for the treatment of skin wounds [ 93 ].…”

Molecular Insights of Hyaluronic Acid as Potential Source of Polymer-Drug Conjugate in the Target-Mediated Treatment of Cancer

“…The naturally occurring polysaccharide hyaluronic acid (HA) is a major component of the extracellular matrix and, additionally, it is found in the synovial fluid of joints and scaffolding that comprises cartilages. Peculiarly, one of its cellular receptors (CD44) it is found over expressed in many cancer cells [1,2]. Structurally, HA consists of β-(1→4)-linked D-glucopyranuronic acid and β-(1→3)-linked 2acetamido-2-deoxy-D-glucopyranose.…”