Study On Zwitterions Modified Chitosan And High Strength Chitosan-based Hydrogels

Chitosan?CS? is an important natural polymer due to its good biocompatibility, antibacterial activity and biodegradability, which made CS a broad application prospect in biomedical field. However, CS is insoluble in neutral, alkaline aqueous and most organic solvents, limiting its biomedical application to some extent. At the same time, biological safety is also a necessary condition for biomedical application. So develop new chitosan derivatives with both good solubility, antibacterial activity and biocompatibility is a significant challenge. Chitosan-based hydrogels is widely employed in controlled drug delivery and tissue engineering in recent years, however, most chitosan-based hydrogels reported are showing poor mechanical property and their biocompatibility still have room for improvement. Therefore,it is very important to improve the mechanical and biological properties of chitosan-based hydrogels.In this thesis, for the purpose of improving the solubility and biocompatibility properties of chitosan, and developing the high strength chitosan-based hydrogel with good biocompatibility, we have synthesized a novel N-quaternary ammonium O-sulfobetaine-chitosan?Q₃BCS? by introducing quaternary ammonium compound?QAC? and sulfobetaine. Its water-solubility, antibacterial activity and biocompatibility were evaluated compare to N-quaternized chitosan and native CS. The high strength chitosan-based hydrogels CS-PHEA DN-gel and CS-PHEA-PDMAPS TN-gel have also been synthesised. The synthesis, mechanical properties, biocompatibility and antibacterial properties were studied systematically. The main content and conclusions are as follows:1. Glycidyl trimethylammonium chloride was used as a N-quaternary ammonium agent. B_y ring opening reaction of epoxy group, we grafted quaternary ammonium molecules to the –NH2 of chitosan, and obtained quaternized chitosan?N-QxCS,x=1³? with different degrees of substitution. Then we selected N-Q₃ CS with good antibacterial properties for further modification. After N-Phthaloylation, grafting NCO-Betaine and unprotect the amine groups, we synthesis the N-quaternized O-sulfobetained chitosan?Q₃B_yCS? with different degrees of substitution successfully. The structure of products were characterized by FTIR?H-NMR?XRD. Water-solubility test show that Q₃ B_yCS have good water solubility from pH 6.5 to pH 11, waters-solubility of Q₃ B_yCS reach up to 200mg/m L. Cell survival rate of Q₃ BCS increased from 30%?N-Q₃CS? to 85% at 2000?g/mL. Furthermore, hemolysis of Q₃ BCS was dropped sharply from 4.07%?N-Q₃CS? to 0.06%. we can conclusion that the introduce of zwitterions can improve the biocompatibility of quaternized chitosan. The antibacterial result show that by further introducing zwitterions, the antibacterial ratio didn't show a noticeable decline compared to N-Q₃ CS.2. The first network of chitosan-based hydrogel with different crosslink density was prepared by adding small cross-linker molecules glutaraldehyde?2%?, then the protonated chitosan-based hydrogel was immersed in an aqueous of HEA until equilibrium was reached. The second network was subsequently polymerized in the presence of the first network, and the CS-PHEA DN-gel was synthesized. Mechanical test indicated that incorporation of first chitosan network with a higher crosslink density results in substantial lowering of the water content and improving of the modulus of the DN-gels. At the same water content, mechanical strength decrease with increasing of crosslink density of DN-gels. When at the same crosslink density, the mechanical strength of DN-gels was improved with the decreasing of water content. It is found that the DN1 gel with 75% water content exhibited the maximum compression strength?84.7 MPa? and 313% elongation.3. Based on the CS-PHEA DN-gel, zwitterions polymer?PDMAPS? was further introduced as a molecular stent network to toughen chitosan-based chitosan and improve its biocompatibility, thus three network CS-PHEA-PDMAPS TN-gel was synthesized. Mechanical test show that TN1 gel possess high strength?tensile stress:0.383MPa; strain:1020%? at 70% water content. In addition, TN gels exhibit excellent biocompatibility. After incubation with cells for 72 h, Cell survival rate of TN-4 gel reach up to 94.4%. Live/Dead assay also confirm its biosafety. Compared to DN gels, TN-gel showing a better antifouling properties.In conclusion, the introduction of zwitterions improving the biocompatibility of both chitosan-based hydrogels and quaternized chitosan, endowing hydrogels with a good antifouling properties. In addition, the introduction of poly-zwitterions as molecular stent can also strengthening the DN-gels.