Study On Preparation And Properties Of Intelligent Hydrogels Based On Poly (Methyl Vinyl Ether-Alt-Maleic Acid)

In order to meet the demands of biomedical research and application, a series of intelligent hydrogels were developed. As novel biomedical polymer materials, intelligent hydrogels show bright application perspective and has become one of the hot research in biomedical field. In this thesis, synthetic polymer poly (methyl vinyl ether-alt-maleic acid) P(MVE-alt-MA), which has good biocompatibility, was chosen as one of the main materials for preparation of intelligent P(MVE-alt-MA) supramolecular hydrogel. Here, several kinds of intelligent supramolecular hydrogel based on P(MVE-alt-MA) were prepared by using different methods. The chemical and physical properties of these intelligent hydrogels were studied systematically. The main content includes:1. Preparation and its stimuli-response of P(MVE-alt-MA)-g-β-CD/P(MVE-alt-MA)-g-Azo supramolecular hydrogel The host polymer P(MVE-alt-MA)-g-β-CD was prepared firstly by the amidation reaction between cyclodextrin derivatives (EDA-6-β-CD) and P(MVE-alt-MA). The guest polymer P (MVE-alt-MA)-g-Azo was then prepared by the amidation reaction between Azo and P(MVE-alt-MA). Mixing host polymer P(MVE-alt-MA)-g-β-CD and guest polymer P(MVE-alt-MA)-g-Azo in water at room temperature will lead to the formation of P(MVE-alt-MA)-g-β-CD/P(MVE-alt-MA)-g-Azo supramolecular hydrogel. This supramolecular hydrogel present an interconnected porous structure and easily adjusted rheological properties, it is not only photo-responsive, but also is pH-responsive. The cytotoxicity of this supramolecular hydrogel was tested by CCK-8 with SKOV3 cells. This supramolecular hydrogel was proved to have no obvious cytotoxicity. The distribution of DiO stained SKOV3 cells in this supramolecular hydrogel was observed by using the laser scanning confocal microscope. SKOV3 cells were alive during the culture period and distributed at the different depth levels in the supramolecular hydrogel SKOV3 cells cultured in hydrogel can succeed desorption by gel-sol transition irradiated by UV light and still survive. This research work based on P(MVE-alt-MA) intelligent hydrogel will provide a theoretical and experimental basis for further study of cells.2. Preparation and its stimuli-response of P(MVE-alt-MA)-g-β-CD/P(MVE-alt-MA)-g-Ad supramolecular hydrogel. The host polymer P(MVE-alt-MA)-g-β-CD was prepared by β-CD grafted P (MVE-alt-MA) using LiH as reaction assistant agent, and the guest polymer P(MVE-alt-MA)-g-Ad was prepared by grafting 1-admantadine hydrochloride (Ad) to P(MVE-alt-MA) with DCC as catalyst. By inclusion complexation between β-CD and Ad, the P(MVE-alt-MA)-g-β-CD/P(MVE-alt-MA)-g-Ad hydrogels can be formed at room temperature. The hydrogel is pH-responsive and has self-healing properties and adjustable rheological properties. This hydrogel was also proved to be cytocompatible and can be used to construct a scaffold for 3D cell culture. This study provides a new way and material for the preparation of functional three-dimensional scaffold.3. Preparation and its properties of P(MVE-alt-MA)/CS complex nanogel. The nanogel based on P(MVE-alt-MA) and chitosan (CS) were prepared by the electrostatic interaction between the carboxyl groups of P(MVB-alt-MA) and the amino group in CS, and schiff base crosslinking between the aldehyde groups of glutaraldehyde (GA) and the amino group in CS. The nanogel was proved to be pH-sensitive. The drug release behavior of the nanogel in vitro was studied using Doxorubicin as the model drug. In vitro drug release test results show that the nanogel is expected to be used as drug carrier.4. Preparation and its properties of P(MVE-alt-MA)-crosslinked-AChS hydrogel. The P(MVE-alt-MA)-crosslinked-AChS hydrogel were prepared by chemical bond crosslinking using EDC/NHS as catalyst and Adipicdihydrazide (ADH) as the cross-linking agent. The complex hydrogel is pH-sensitive, without obvious cytotoxicity to the cells in the appropriate concentration conditions, and the SKOV3 cells can survive in the hydrogel, which is expected to be used as a cell culture scaffold. This study provides the basis for the preparation of natural polymer and synthetic polymer composite hydrogel and its application in three-dimensional cell culture.On the whole, a series of intelligent hydrogels based on P(MVE-alt-MA) were prepared, and these P(MVE-alt-MA) intelligent hydrogels can be served as powerful platform for biomedical research and application, especially for 3D cell culture in vitro and as drug release carrier.