Glycosaminoglycans (GAGs) are a family of linear polysaccharides that can generally be described as an alternating copolymer and are found in all animal tissues. The repeat units of GAGs consist of a hexamine unit (glucosamine or galactosamine) and a sugar (galactose, glucuronic acid, or iduronic acid). GAGs are found on cell surfaces in the extracellular matrix and are well preserved among species. When GAGs are bound to a protein core the resulting macromolecule is termed a proteoglycan and often is described as having a “bottle brush” like configuration. The molecular weights of GAGs range from 5 to 5000 kDa. There are several specific GAGs used as biomaterials including heparin, heparan sulfate, keratan sulfate, dermatan sulfate, chondroitin sulfate and HA. GAGs are naturally degraded by enzymes such as hyaluronidase, chondroitinase, and heparanase.
Heparin is a highly sulfated GAG and is widely used as an anticoagulant. Due to the sulfation levels it is very strongly negatively charged. Pharmaceutical heparin is commonly derived from bovine or porcine mucosal tissues. Heparin is closely related to heparan sulfate and is composed of variably sulfated disaccharides. The predominant saccharide units are D-glucosamine and uronic acid (either D-glucuronic acid or L-iduronic acid) with sulfation of some hydroxyl groups.
Chondroitin sulfate (CS) is also a negatively charged GAG but is composed of repeating glucuronic acid and N-acetylgalactosamine units. Thus each disaccharide unit contains a sulfate and carboxyl group available for modification. CS is a major component of cartilage tissue and being capable of readily absorbing water is credited for the compressive strength of that tissue. Chondroitin sulfate is often sourced from shark cartilage.
HA, also commonly termed hyaluronan, hyaluronate, or sodium hyaluronate, is unique from other GAGs in that it exists in much higher molecular weights (50-5000 kDa), is excreted from cells, and does not bind to a protein core. HA has been extensively studied as a biomaterial in part due to these unique properties.