Supramolecular self-assembly of glycosaminoglycan mimetic nanostructures for cell proliferation and 3D cell culture application

Glycosaminoglycans (GAGs), such as heparin, heparan sulfate and chondroitin sulfate, are playing important roles in various biological processes. Due to the laborious work of organic or enzymatic total synthesis of GAGs, different approaches, including glycopolymers, dendrimers, etc., have been developed to mimic the structures and bioactivities of GAGs, but the syntheses can still be difficult. In the current study, a new format of GAG mimetic structure, supramolecularly assembled polymers, have been easily prepared by mixing fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) and sulfated glyco-modified fluorenylmethoxy derivatives (FGS and FG3S). The self-assembly behavior of these polymers into different structural formats of nanoparticles, nanofibers and macroscopic hydrogels upon adjusted concentrations and composite ratios have been detailed studied. The nanofibers modified with highly sulfated glycol groups (FG3S/Fmoc-FF) showed strong promotion effect for cell proliferation, which efficiency was even similar to that of natural heparin, higher than nanoparticles or non-/low-sulfated glyco-modified nanofibers. Moreover, the supramolecular polymers were further made into hydrogels that capable of 3D cell culture. This study provided a novel and efficient approach for GAG mimicking, showing great potential for tissue engineering related applications.