Effect of chemical modification on physicochemical and biological properties of chondroitin sulfate

Chondroitin sulfate (CS) derivatives are useful biomacromolecules for fabrication of biomaterials. However, chemical modifications of CS molecular structure during processing may alter its physicochemical and biological properties. Here, we studied these changes in molecular and biological functions following CS oxidation to different oxidation. Under ultraviolet visible (UV-Vis) spectroscopy, CS exhibited a blue shift in characteristic absorption peaks after the oxidation. The thermo-stability of the modified CS was also weaker than its original molecular form. Both FTIR and NMR results demonstrated distinct structural changes at the molecular level after oxidation. In vitro study showed that rabbit bone marrow stromal cells cultured with oxidized CS (CSA) containing cell culture medium exhibited viability comparable to normal cell culture medium for CSA concentration less than 125 mg/mL. However, CSA may also inhibit proliferation of these cells. Besides, unmodified CS could induce a chondrogenesis of stem cells, but this function was weakened after chemical modification. Interestingly, chemical modification altered physicochemical and biological properties in substitution degree-dependent manner with the highly oxidized CS exhibiting the lowest stability and chondrogenic induction. These results indicated that chemical modification of biomacromolecules, such as CS, could change both their physicochemical properties and biological functions, suggesting the need to carefully control parameters during biomaterial processing and fabrication.