Aminooxy Pluronics: Synthesis and Preparation of Glycosaminoglycan Adducts

Abstract

Novel biomaterials have been prepared in which glycosaminoglycans (GAGs) are chemically modified to create amphiphilic multiblock copolymers that are able to adhere to hydrophobic surfaces and can self-assemble into cross-linker-free hydrogels. First, the triblock poly(ethylene oxide)-polypropylene oxide copolymers (Pluronics) were converted into the previously unknown aminooxy (AO) derivatives. Both mono-AO and bis-AO Pluronics (AOPs) were synthesized and fully characterized in order to prepare tetrablock and pentablock copolymers, respectively. Second, the AOPs were coupled to the uronic acid carboxylates of heparin (HP) and hyaluronic acid (HA) using carbodiimide chemistry in order to give the previously undescribed amidooxy GAG derivatives. The coupling chemistry was confirmed using a newly prepared fluorescent AO reagent. Third, AOP-heparin and AOP-fluorescently labeled heparin were shown to adsorb efficiently to polystyrene surfaces, as determined by IL-8 based ELISA and fluorescence measurements, respectively. Fourth, AOP-linked fluorescently labeled HA was shown to adsorb efficiently to plastic surfaces. Finally, three different AOPs were evaluated for self-assembling hydrogel formation by AOP-HA pentablock polymers. In short, AOP-GAG adducts are semisynthetic amphiphilic biomacromolecules that offer a range of valuable practical opportunities for surface modification, preparation of cross-linker-free hydrogels, and formation of self-assembling mimics of the extracellular matrix.