Preparation And Application Of Biodegradable Hydrogel And Functionalized Micelle Based On Polycaprolactone

Hydrogel is a sort of polymeric material which owns three dimensional networks. Hydrogel is insoluble in water and can swell in aqueous medium, thus it can absorb plenty of water and keep the water well. Hydrogels for cell encapsulation and proliferation are of importance in tissue engineering since hydrogels own the excellent property in permeability, which allows diffusion and transport of essential materials, such as oxygen, nutrients for cells. Owing to the excellent property, biodegradable hydrogels were widely utilized in tissue engineering and drug delivery. Highly swollen hydrogels provide a tissue-like microenvironment for cells. The high water content promotes facile transport and can be tuned to permit long-term cell survival.In chapter 1, the classification of hydrogel, the gel formation mechanism of intelligent hydrogel and the application in tissue engineering was reviewed. In addition, the classification of functionalized micelles and their application in drug delivery was also reviewed.In chapter 2, a series of biodegradable AC-PCL-HEMA/PAAc hydrogels were synthesized. The degradation of hydrogel was obviously accelerated in the presence of pseudomonas lipase due to the catalytic effect of the lipase on the degradation of PCL chains in the hydrogel network. The hydrogel exhibited pH sensitivity and a higher swelling ratio was observed in the solution with a higher pH value. The in vitro release of BSA from the hydrogel demonstrated that the hydrogel with a lower crosslinking density had a higher release rate. The cell culture on the hydrogels showed that the cells can adhere, and spread on the hydrogel surfaces as well as migrate inside the hydrogel networks.In chapter 3, supramolecular hydrogels consisting ofα-cyclodextrin and MPEG-PCL-MPEG triblock polymers were prepared and characterized in vitro and in vivo. The hydrogels were suitable for injection through a small-diameter aperture. The sustained release of the dextran-FITC from the hydrogels, which lasted for more than one month, indicated the hydrogels were promising for drug delivery. Due to the rapid gelation property, the hydrogels could effectively entrap biologically active additives such as drugs and cells for in situ injection. ECV304 and MSC cells were encapsulated in hydrogel and the cell morphologies could be kept the during the cell culture. The in vitro cytotoxicity and the in vivo histological studies demonstrated that the hydrogels had great potential as the injectable scaffolds for tissue engineering applications due to their good biocompatibility.In chapter 4, Dex-PCL-HEMA/PNIPAAm hydrogels were synthesized and characterized in vitro and in vivo. The hydrogels exhibited a phase transition temperature at 33.2℃, which was suitable for injection through a small-diameter aperture. The sustained release of the BSA from the hydrogel was observed when the temperature was higher than the LCST of the hydrogel. Cell viability studies in vitro and the histological studies in vivo demonstrated that the hydrogel was a promising candidate of an injectable polymer scaffold for tissue engineering applications.In chapter 5, galactosylated and FITC conjugated Gal-PCL-g-Dex-FITC grafted polymers were fabricated. The resulting polymers are able to self-assemble to form stable micelles in vitro and in vivo. The galactosylated and fluorescence labeled micelles could be selectively recognized by HepG2 cells and subsequently accumulate in HepG2 cells. Importantly, the liver targeting effect of the galactosylated micelles was clearly demonstrated by the fluorescence distribution of the micelles in liver tissue.In chapter 6, galactosylated and mono-aminoporphyrin (APP) grafted poly(2-aminoethyl methacrylate)-b-polycaprolactone (Gal-APP-PAEMA-PCL) and APP-PAEMA-PCL polymers were fabricated by the combination of ring opening and RAFT polymerization. The resulting polymers are able to self-assemble to form stable micelles. Compared to the APP-PAEMA and APP-PAEMA-PCL, the fluorescence intensity of the Gal-APP-PAEMA-PCL is higher than those of the formers whenever in DMSO or PBS (pH 7.4). None of the porphyrin based block polymers exhibits dark cytotoxicity to both HEp2 cells and HepG2 cells at a concentration of 1 mg/mL. Importantly, the galactosylated micelles could be selectively recognized by HepG2 cells and subsequently preferentially accumulated in HepG2 cells and had the higher dark and phototoxicity effect.