The Studies On The Preparation And Application Of Several Three Dimensional Assemblies Of Thermosensitive Microgels

Poly (N-isopropylacrylamide)(PNIPAM) microgel is a common thermosensitive material. Its volume phase transition temperature (VPTT) is about31℃, very close to the body temperature. At low temperature, PNIPAM microgel is relatively hydrophilic, and the microgel particles are highly swollen; when the temperature rises above the volume phase transition temperature, the microgel becomes relatively hydrophobic, so the particles shrink sharply. PNIPAM microgels are widely used in the biomedical field, especially in controlled drug delivery, biosensing and tissue engineering. Not only have the dispersed PNIPAM microgels have been exploited for applications, recent studies reveal that they can also easily be assembled to form two-dimensional (2D) or three-dimensional (3D) assemblies. The2D assemblies include self-assembled monolayer and layer-by-layer (LBL) multilayer films.3D assemblies consist of ordered three-dimensional colloidal crystal and hydrogel without an ordered structure formed by the aggregation of microgels. Herein, the researches about the preparation and application of3D PNIPAM microgel assemblies were conducted further.A series of PNIPAM microgels with different sizes were synthesized by varying the content of the surfactant. By a simple heating-cooling cycle,3D binary colloidal crystal (binary CC) assemblies of soft PNIPAM microgels with different sizes were fabricated for the first time. According to reflectance spectroscopy, differential interference contrast microscopy, and other characterization methods, the large microgel spheres are organized into face-centered cubic (fcc) structure, the small spheres are located within the octahedral voids formed by large microgels, resulting in a binary colloidal crystal with a NaCl structure. The size ratio and the number ratio of large microgel spheres and small spheres will have an impact on the degree of crystallinity of formed binary CCs. The stop band of binary CCs can be tuned by changing the concentration of the microgel dispersion; the intensity of the diffraction peaks can also be adjusted by the introduction of hard spheres. The microgel binary CCs can also respond to the temperature. The new3D colloidal crystal assemblies are expected to find applications in fields such as sensing and displaying.By thermally induced gelation, microgels can form3D hydrogel assembly which could be used as cell scaffold. When cultured in the hydrogel scaffold, cells could grow in the scaffolds and form multicellular spheroids. But the process of cell aggregation and formation of multicellular spheroids was very slow. By Michael reaction, chitosan can be soluble at physiological conditions. When mixed with the cells with aldehyde groups on the surfaces after treatment with sodium periodate, the cells could be aggregated quickly and efficiently by the formation of Schiff base. By adjusting the content of chitosan and the aggregation time, we can regulate the aggregation behavior of cells. Formed cell aggregates still have good activity and the ability of protein secretion. This simple aggregation method is applicable to a variety of cells, and shows no effect on the viability of cells. When the formed cell aggregates are embedded in the PNIPAM/PEG (Polyethylene glycol) hydrogel scaffolds, an accelerated generation of multicellular spheroids will happen. Both the size of the multicellular spheroids and the number of cells will increase significantly, which meet the need of organ printing.An important method to make microgels multi-functional is to prepare microgels with core-shell structure. Several series of poly(N-isopropylacrylamide-co-acrylic acid)(P(NIPAM-AA))(core)/poly(N-isopropylacrylamide)(PNIPAM)(shell) core-shell microgels and inverse PNIPAM/P(NIPAM-AA) core-shell microgels, with different degree of crosslinking in the core or shell, were prepared by precipitation polymerization. Their thermosensitive behaviors at different pH were studied by dynamic light scattering. The formation of3D hydrogel assemblies by the gelation of these soft core-shell microgels was investigated by dynamic temperature ramp test (DTRT) of rheometry for the first time. Surprisingly, when the temperature reached the gelation temperature (Tg) of pure shell microgels, these core-shell microgels still could not form a gel. Tg of core-shell microgels is far larger than that of pure shell microgels. The thinner the shell is, the higher the Tg is. When increasing the degree of crosslinking in the core, Tg will decrease; while increasing the degree of crosslinking of the shell, there is no significant change of Tg. By reducing the pH value, Tg will also decrease. And the decreased tendency of Tg is consistent with the decreased tendency of the charge of AA group caused by the reduced pH. We think the reason is that some restricted relatively hydrophilic groups or chain segments of core region, may be induced to stretch out to the periphery of the core-shell microgels by the inner channels of thin shell microgels, when the temperature is higher than the Tg of shell microgels. The results of zeta potential and turbidity also supported this conclusion. These results imply important basis in using core-shell microgels as hydrogel cell scaffold and drug release carrier for3D cell culture.