Chemical modification of hyaluronic acid by carbodiimides

Abstract

Hyaluronic acid (HA) is a linear polysaccharide with repeating disaccharide units of glucuronic acid and N-acetylglucosamine and is found in the extracellular matrix of connective tissues. Reaction of high molecular weight sodium hyaluronate (NaHA, MW approximately 2 x 10(6] with EDC at pH 4.75, either in the presence or absence of a primary diamine, gave the N-acylurea and O-acylisourea as NaHA-carbodiimide adducts. None of the expected intermolecular coupling with the amine component was observed. On the basis of this new observation, this method for chemical modification of HA was used in conjunction with new synthetic carbodiimides to prepare HA derivatives bearing lipophilic, aromatic, cross-linked, and tethered functional groups. The degree of conversion to NaHA-acylurea products appears to depend upon both the characteristics of various carbodiimides and the conformational structure of NaHA.

Optimization of surface modifications of extrasynovial tendon to improve its gliding ability in a canine model in vitro

“…[16][17][18] The modification of glucuronamides such as HA requires the activation of carboxyl groups, which can be accomplished by using a watersoluble carbodiimide such as 1-ethy 1-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC). EDC activates the carboxyl groups of the HA molecule and forms the intermediate Oacylisourea, which can chemically bind to exposed amino groups, such as those that exist in the collagenous tendon matrix, forming a new collagen-HA polymer, fixed to the tendon surface.…”

Surface Treatment of Flexor Tendon Autografts with Carbodiimide-Derivatized Hyaluronic Acid<sbt aid="1047845">An in Vivo Canine Model</sbt>

“…Maintaining a strong attachment between hyaluronic acid and the tendon surface may actually be more important than the absolute concentration of the hyaluronic acid, as abrasion during tendon gliding constantly threatens to remove hyaluronic acid from the tendon surface. Recently, carbodiimide derivatization has been developed to modify hyaluronic acid (cd-HA) for clinical use [37][38][39] . Modification of glucuronides requires activation of the carboxyl groups, which can be accomplished with use of a water-soluble carbodiimide such as 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) as the condensing agent.…”

Photopatterned collagen–hyaluronic acid interpenetrating polymer network hydrogels

“…The turnover rate of HA in the body is rapid. Attempts have been made to create crosslinked HA scaffolds by employing various crosslinking methods, including carbodiimide crosslinking [47,48], divinyl sulphone crosslinking [49], disulphide crosslinking [17], hydrazide crosslinking [17] and photocrosslinking [35,47]. We have modified HA and attached a photocrosslinkable moiety using an already established protocol [35].…”