Synthesis, characterization and chondroprotective properties of a hyaluronan thioethyl ether derivative

Abstract

Hyaluronan (HA), a non-sulfated glycosaminoglycan, is widely used in the clinic for viscosurgery, viscosupplementation, and treatment of osteoarthritis. Four decades of chemical modification of HA have generated derivatives in which the biophysical and biochemical properties, as well as the rates of enzymatic degradation in vivo have been manipulated and tailored for specific clinical needs. One earlier modification adds multiple thiol groups to HA through hydrazide linkages, leading to a readily crosslinkable material for adhesion prevention and wound healing. We now describe the synthesis and chemical characterization of a novel thioethyl ether derivative of HA, HA-sulfhydryl (HASH), with a minimal tether between the HA and the thiol group. Unlike earlier thiol-modified HA derivatives, HASH cannot be readily crosslinked to form a hydrogel using either oxidative or bivalent electrophilic conditions, thus offering a unique polymeric polythiol that remains soluble. Moreover, HASH showed no cytotoxicity towards primary human fibroblasts and reduced the apoptosis rates of primary chondrocytes exposed to hydrogen peroxide in vitro. These properties foreshadow the clinical potential of HASH to moderate inflammation and to act as a chondroprotective agent in vivo.

Hydrogels with time-dependent material properties enhance cardiomyocyte differentiation in vitro

“…HA is a natural, non-immunogenic [31] ECM component that can be easily modified to display various chemistries [26, 32, 33]. HA was thiolated using the carbohydrate selective, sulfhydryl-reactive crosslinker (3-[2-Pyridyldithio]propionyl hydrazide) and upon reduction, a free thiol was added to the end of the carboxyl group (see Fig.…”

Emerging intra-articular drug delivery systems for the temporomandibular joint

“…Nevertheless, recent progress in the field of injectable biomaterials shows great promise for the development of superior intra-articular therapies. Novel HA-based materials have the potential to improve viscosupplementation and joint regeneration strategies [66, 67]. In a recent study, intra-articular delivery of basic fibroblast growth factor using an HA vehicle significantly improved osteochondral repair in the knee joint of a rabbit model [68].…”

A Novel Cross-Linked Hyaluronic Acid Porous Scaffold for Cartilage Repair

“…It serves as the anchor of large proteoglycan aggregates within tissues and maintains tissue hydration by immobilizing ions and water, has a central role in lubrication and shock absorption in joints and modulates cell migration, inflammatory processes, and angiogenesis. 28 In order to prolong its degradation rate and to improve its mechanical stability, modified and cross-linked derivatives have been developed 22,[29][30][31][32][33] and have already found multiple biomedical applications ranging from viscosupplementation, 34,35 viscosurgery, wound healing, and drug delivery 30 to tissue engineering. For its use in tissue engineering, HA can be fabricated in multiple forms: as hydrogels 18,25,36 , woven meshes, 26 nonwoven fibers, 9 and porous sponges.…”