Biomimetic synthesis of chondroitin sulfate-analogue hydrogels for regulating osteogenic and chondrogenic differentiation of bone marrow mesenchymal stem cells

As a typical representative of crucial glycosaminoglycans (GAGs), chondroitin sulfate (CS) with sulfonated polysaccharide in structures extensively exists in the extracellular matrix (ECM) and exhibits peculiar bioactivity on the regulation of cells behaviors and fates (e.g. proliferation and differentiation) in organisms. Nevertheless, some intrinsic disadvantages of natural CS mainly ascribe to the intricate structure and inhomogeneous composition (especially the uncontrollable sulfonate degrees), resulting in overt restrictions on its physiological functions and applications. Although recent bionic synthesis of artificial GAGs analogues at the molecular level have already provides an efficient strategy to reconstruct GAG for regulating the cellular behaviors and fates, it still remains great challenges to rationally design and synthesize GAGs analogues with special composition and structure for precisely mimicking ECM. Simultaneously, the relevant regulation process of GAG analogues on cell fate needs to be further studied as well. Herein, chondroitin sulfate-analogue (CS-analogue) hydrogels with diverse contents of saccharide and sulfonate units in the networks were fabricated through photo-polymerization and then characterized by Fourier transform infrared (FT-IR) spectroscopy, zeta potential and scanning electron microscope (SEM). Additionally, CS-analogue hydrogels with proper mechanical properties exhibited favorable swelling, degradation performance and prominent cytocompatibility. According to cell cultivation results, CS-analogue hydrogel with a certain proportion of saccharide and sulfonate units presented preferable promotion on the adhesion, spreading, proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs), shedding light on the significance of saccharide and sulfonate units in regulating cell behaviors. Furthermore, BMSCs cultivated with CS-analogue hydrogels under different culture conditions were also systematically investigated, revealing that with the help of cultivation environment CS-analogue hydrogels owned the remarkable capacity of directing either chondrogenic or osteogenic differentiation of BMSCs. Therefore, it is envisioned that versatile CS-analogue hydrogels would have promising application prospects in the biomedical and clinical fields.