Bioactivities Of Sulfated Chitosan With Defined Sulfation Sites

Heparin/heparan sulfate(HS) is an important member of the glycosaminoglycan family and possesses a variety of biological functions. It can bind to many extracellular matrix proteins and signal molecules, and can regulate a wide variety of biological activities. As an analog of heparin, sulfated chitosan has similar structure with heparin/HS. The sulfate groups and the specific saccharide structure in sulfated chitosan can regulate protein-binding activity as that of heparin/HS does. So, sulfated chitosan can achieve the similar biological functions as that of heparin/HS, including anticoagulation, antivirus, anti-tumor, antibacteria and promoting the differentiation of stem cells and so on. Compared with heparin/HS, sulfated chitosan has the advantages of stable activity and controllable structure, giving it a wonderful prospect of application. Therefore, it is very important to investigate the biological function of sulfated chitosan.In this thesis, a series of sulfated chitosans with defined sulfation sites were prepared to investigate the effects of sulfation sites and structure on cell proliferation and differentiation. Furthermore, the modification of sulfated chitosan on chitosan film would enhance its antibacterial activity and increase cell proliferation. Details are as follows:1. A series of regioselective sulfated chitosans were synthesized by chemical modification. Different cells were cultured in the medium with sulfated chitosans added, the results indicated that the sulfated chitosans can promote cell proliferation.2. Sulfated chitosans can influence the differential behavior of stem cells. Embryonic stem cells(mESCs) were cultured in medium supplemented with different sulfated chitosans, and the results indicated that sulfated chitosan with different sulfation sites showed different capabilities for inducing the neural differentiation of mESCs. Compared with the other chitosans, 6-O-sulfated chitosans(6S) promoted the neural differentiation of ESCs most efficiently. In addition, 6S with higher sulfation degree better enhanced neural differentiation, indicating that the promotion of neural differentiation was the combinational result of sulfated sites and sulfation degree of the sulfated chitosan.3. Chitosan film can be modified by 6S through binding effect of negative and positive ions, with the assistance of glutaraldehyde cross-linking. The modified membrane showed good biocompatibility, it can enhance antibacterial effect and promoting cell proliferation.Our study showed that sulfated chitosan with defined sulfation site displayed various bioactivities including promoting cell proliferation, inducing specific differentiation of stem cells and antibacterial effect. Biomaterials modified with sulfated chitosan exhibited excellent antibacterial effect and were able to promote cell proliferation, which have potential application in preparing multifunctional tissue-inducing materials.