Synthesis and Characterization of Proteoglycan-Mimetic Graft Copolymerswith Tunable Glycosaminoglycan Density.

Proteoglycans(PGs) are important glycosylated proteins found onthe cell surface and in the extracellular matrix. They are made upof a core protein with glycosaminoglycan (GAG) side chains. Variationsin composition and number of GAG side chains lead to a vast arrayof PG sizes and functions. Here we present a method for the synthesisof proteoglycan-mimetic graft copolymers (or neoproteoglycans) withtunable GAG side-chain composition. This is done using three differentGAGs: hyaluronan, chondroitin sulfate, and heparin. Hyaluronan isfunctionalized with a hydrazide-presenting linker. Either chondroitinsulfate or heparin is grafted by the reducing end on to the hyaluronanbackbone through reductive amination. PG mimics with heparin or chondroitinsulfate side chains and four different ratios of GAG side chain resultin graft copolymers with a wide range of sizes. The chemistry is confirmedthrough attentuated total reflectance Fourier transform infrared spectroscopy(ATR-FTIR) and 1H NMR. Effective hydrodynamic diameterand zeta potential are determined using dynamic light scattering andelectrophoretic mobility measurements. Graft copolymers were testedfor their ability to bind and deliver basic fibroblast growth factor(FGF-2) to mesenchymal stem cells (MSCs). The chondroitin sulfate-containinggraft copolymers successfully deliver FGF-2 to cells from surfaces.The lowest graft density of heparin-containing PG mimic also performswell with respect to growth factor delivery from a surface. This newmethod for preparation of GAG-based graft copolymers enables a widerange of graft density, and can be used to explore applications ofPG mimics as new biomaterials with tunable biochemical and biomechanicalfunctions. [ABSTRACT FROM AUTHOR]