Naizhen Zhou

In situ formation of multiple stimuli-responsive poly[(methyl vinyl ether)-alt-(maleic acid)]-based supramolecular hydrogels by inclusion complexation between cyclodextrin and azobenzene

Biocompatible external stimuli-responsive hydrogels are of interest for drug delivery, cell and gene therapy, tissue engineering, protein patterning, and other biomedical applications. In this work, based on the biocompatible polymer poly(methyl vinyl ether-alt-maleic acid) (P(MVE-alt-MA)), host polymer β-cyclodextrin-grafted P(MVE-alt-MA) (P(MVE-alt-MA)-g-β-CD) and guest polymer azobenzene-grafted P(MVE-alt-MA) (P(MVE-alt-MA)-g-azo) were first prepared. Then through taking advantage of the traditional host–guest interaction of β-cyclodextrin and azobenzene, novel multiple stimuli-responsive physical P(MVE-alt-MA)-g-β-CD/P(MVE-alt-MA)-g-azo supramolecular hydrogels were obtained after simply mixing the aqueous solutions of the host polymer and guest polymer. The formation of the supramolecular hydrogels was also confirmed by 2D-NOESY. This kind of supramolecular hydrogels not only exhibits photo-, pH- and thermo-sensitivity, but also cytocompatibility. Ovarian cancer SKOV3 cells can survive within different hydrogel layers, which were observed by confocal microscopy. These results suggest that this multiple stimuli-responsive P(MVE-alt-MA)-based supramolecular hydrogel may be expected to have a powerful potential in biomedical applications as a three-dimensional (3D) cell culture matrix or as a vehicle for the delivery of drugs and therapeutic cells.

Sliced Magnetic Polyacrylamide Hydrogel with Cell-Adhesive Microarray Interface: A Novel Multicellular Spheroid Culturing Platform

Cell-adhesive properties are of great significance to materials serving as extracellular matrix mimics. Appropriate cell-adhesive property of material interface can balance the cell-matrix interaction and cell-cell interaction and can promote cells to form 3D structures. Herein, a novel magnetic polyacrylamide (PAM) hydrogel fabricated via combining magnetostatic field induced magnetic nanoparticles assembly and hydrogel gelation was applied as a multicellular spheroids culturing platform. When cultured on the cell-adhesive microarray interface of sliced magnetic hydrogel, normal and tumor cells from different cell lines could rapidly form multicellular spheroids spontaneously. Furthermore, cells which could only form loose cell aggregates in a classic 3D cell culture model (such as hanging drop system) were able to be promoted to form multicellular spheroids on this platform. In the light of its simplicity in fabricating as well as its effectiveness in promoting formation of multicellular spheroids which was considered as a prevailing tool in the study of the microenvironmental regulation of tumor cell physiology and therapeutic problems, this composite material holds promise in anticancer drugs or hyperthermia therapy evaluation in vitro in the future.

Self-healing pH-sensitive poly[(methyl vinyl ether)-alt-(maleic acid)]-based supramolecular hydrogels formed by inclusion complexation between cyclodextrin and adamantane

Self-healing materials are of interest for drug delivery, cell and gene therapy, tissue engineering, and other biomedical applications. In this work, on the base of biocompatible polymer poly(methyl vinyl ether-alt-maleic acid) (P(MVE-alt-MA)), host polymer β-cyclodextrin-grafted P(MVE-alt-MA) (P(MVE-alt-MA)-g-β-CD) and guest polymer adamantane-grafted P(MVE-alt-MA) (P(MVE-alt-MA)-g-Ad) were first prepared. Then through taking advantage of the traditional host-guest interaction of β-cyclodextrin and adamantane, a novel self-healing pH-sensitive physical P(MVE-alt-MA)-g-β-CD/P(MVE-alt-MA)-g-Ad supramolecular hydrogels were obtained after simply mixing the aqueous solution of host polymer and guest polymer. This kind of supramolecular hydrogels not only possess pH-sensitivity, but also possess the ability to repair themselves after being damaged.

Poly(dopamine)-inspired surface functionalization of polypropylene tissue mesh for prevention of intra-peritoneal adhesion formation

Polypropylene (PP), as one of the most common prosthetic materials, has been widely used in intra-peritoneal repair. However, its adhesion to viscera has severely limited its application. Therefore it is critical to improve the PP surface with an anti-adhesion property. In this work, based on dopamine-inspired chemistry, virgin PP (V-PP) mesh was first pretreated with O2 plasma, subsequently dipped in dopamine aqueous solution for 24 h, and then chitosan (CS) was grafted onto it. Finally the anti-adhesion mesh (O-PP/PDA/CS) was obtained. The formation procedure of a PDA/CS ad-layer was characterized by water contact angle measurements, ATR-FTIR, SEM, and XPS. The results show that a PDA/CS ad-layer could be coated on the PP surface efficiently. NIH/3T3 cells were first cultured on O-PP/PDA/CS meshes to evaluate the availability of anti-adhesion and biocompatibility in vitro, and then the efficacy of the PDA/CS-coating as a barrier for reducing postsurgical adhesions was evaluated using a rat abdominal wall defect model. Compared with the V-PP group, NIH/3T3 cells exhibited higher viability in the O-PP/PDA/CS groups as evaluated by the CCK-8 method. In addition, NIH/3T3 cells grow into round-shapes on the O-PP/PDA/CS surface. This indicates that the modification strategy can facilely lead to excellent properties of anti-adhesion. In vivo tests further indicate that O-PP/PDA/CS meshes were effective in reducing adhesion formation.

The effects of macroporosity and stiffness of poly[(methyl vinyl ether)-alt-(maleic acid)] cross-linked egg white simulations of an aged extracellular matrix on the proliferation of ovarian cancer cells

Ageing and remodelling of the extracellular matrix (ECM) leads to enzyme activation, resulting in a fibrotic microenvironment and fluctuating ECM stiffness. In this study, prepared egg white (EW) cross-linked with poly[(methyl vinyl ether)-alt-(maleic acid)] (P(MVE-alt-MA)) with macroporous structures were used to simulate an aged extracellular matrix that affected the malignant behaviour of cancer cells at different stages. Increased macroporosity and stiffness properties clearly enhanced the proliferation of cancer cells. In other words, different levels of EW cross-linking had different effects on cell malignancy, thereby determining the ability and speed of cell migration in scaffolds. The study showed that porosity and stiffness changes in the matrix were possible mechanisms for cancer cell invasion and metastasis besides blood vessels and lymphatic invasion in human body. P(MVE-alt-MA)-cross-linked EW contained a major component of ECM and provided a useful model to evaluate the proliferation and metastasis of cancer cells in vitro. This has important significance when it comes to exploring the effects of the material microenvironment on tumour prevention and treatment.

Thermo-Sensitive PLGA-PEG-PLGA Tri-Block Copolymer Hydrogel as Three-Dimensional Cell Culture Matrix for Ovarian Cancer Cells

Thermo-sensitive hydrogels which could encapsulate cells and provide a three dimensional (3D) microenvironment have great potential in building new cell culture models in vitro. In this study, a thermal responsive hydrogel based on PLGA-PEG-PLGA tri-block copolymers was developed as matrix for 3D ovarian cancer cell culturing. The gelation of PLGA-PEG-PLGA tri-block copolymer was concentration-dependent. SEM images showed the pores were suitable for the formation of 3D cell structures. Cell morphological results showed that large aggregates of ovarian cancer cells (HO8910) were formed after cultured for 10 days. Therefore, hydrogel based on PLGA-PEG-PLGA tri-block copolymers hold potential as in vitro cell culture matrix for ovarian cancer cells.

H727 Multicellular Spheroids and Its Resistance to Antitumor Drugs Sunitinib and Axitinib

The three-dimensional (3D) culture model of neuroendocrine tumor H727 cells was established by using the agarose gel as culture matrix, which provided a new method for drug screening of neuroendocrine tumors. As VEGFR inhibitor, sunitinib and axitinib were applied to inhibit human neuroendocrine H727 cell line in two-dimensional (2D) and 3D culture models. The inhibitory rate of H727 cells with different drug concentration were assessed by CCK-8 assay method and combined with using the FDA/PI double staining and the digital microscope analysis system. When the concentration of sunitinib ≥4.0 μmol/L, the H727 spheroids began to split, and the apoptosis of H727 cells occurred, the sizes of multicellular spheroids was significantly reduced in the groups of high-dose axitinib. These results illustrated that sunitinib and axitinib can effectively inhibit the growth and proliferation of neuroendocrine tumor H727 cells. Sunitinib and axitinib can also promote apoptosis of H727 cells.