•GP cross-linked EW was prepared for ageing ECM biomimetic microenvironment in cell culture.•The porosity and mechanical properties of the ECM-mimetic GP cross-linked EW facilitated cell proliferation and aggregation.•Prevention and treatment of cancers should focus on drugs that can prevent age-induced degenerative changes in the ECM.Cancer is closely associated with aging of the body. Aging of the extracellular matrix (ECM) leads to a fibrotic microenvironment and increasing stiffness of ECM. In this study, the porosity and stiffness were advantageous to the proliferation and aggregation of ovarian SKOV-3 cancer cells. Both the porosity and stiffness increase could lead to enhancement of proliferation and aggregation of ovarian SKOV-3 cancer cells. Further studies aimed at preventing tumoral invasion and metastasis should focus on drugs that can prevent age-induced degenerative changes in the ECM.Download high-res image (105KB)Download full-size image

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.

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.

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.

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.

•Ovarian SKOV-3 cancer cells could form into multicellular aggregates (MCS) in GA cross-linked egg white (EW) with higher elastic modulus.•The higher elastic modulus G′ of EW is more beneficial to the proliferation and migration of SKOV-3 cells.•The degradable GA cross-linked EW is potential 3D cell culture matrix economically.The extracellular matrix (ECM) regulates cellular behaviours in a way that it is still far from completely understood, especially in cancer research field. Here we showed a simple system based on different glutaraldehyde (GA) cross-linked egg white (EW) that supported growth of cells on three dimensional (3D) scaffolds. The reaction between GA and EW was highly active. The pore distribution in GA cross-linked EW was more uniform. The mechanical properties of GA cross-linked EW can be tuned through changing the amount of added GA. Overall, the EW based scaffolds were promising tools that may be used as tunable 3D materials in vitro platforms for cancer tissue engineering and anticancer drugs resistance testing.

For mimicking the fibrous extracellular matrix (ECM), a facile method for patterning anticell adhesive substrate was novelly applied on agarose hydrogel. Without using masks or templates for etching, we applied the magnetic field-induced colloidal assembly of magnetic nanoparticles on the flat agarose hydrogel to form cell-adhesive micropatterns. Meanwhile, tuning the hydrogel substrate’s modulus to fit real tissue was experimentally demonstrated. Magnetic nanobeads were also assembled on this hydrogel surface and formed more complete and regular patterns. The patterned hydrogel substrate could actually influence behaviors of different cancer cells, including adhesion, growth, and migration.Keywords: agarose hydrogel; cell-adhesive micropatterns; magnetic nanomaterials; magnetostatic field induced assembly; tumor-associated ECM

•Ovarian cancer cell line HO8910 can better grow on PLGA microspheres.•Collagen I coated PLGA microsphere promoted the adhesion and growth of HO8910 cells.•HO8910 cells grew on PLGA microspheres increased expression of E-cadherin.In this study, we prepared surface-smooth and porous poly(lactic-co-glycolic acid) (PLGA) microspheres with different diameters, different sizes of pores and different densities of pores using a simple oil/water emulsion method and varying the preparation conditions, including the molecular weight of PLGA, the components of the PLGA and the addition of porogen. The surface-smooth nonporous and porous PLGA microspheres were also further modified with collagen I. The characteristics of these PLGA microspheres, including original and collagen I-coated PLGA microspheres, were evaluated in a three-dimensional (3D) culture of ovarian cancer HO8910 cells. The HO8910 cells can growth better on original porous and collagen I-coated PLGA microspheres, and express remarkably E-cadherin. These results indicate that porous PLGA microspheres and collagen-coated PLGA microspheres are promising candidates as ovarian cancer cell culture microcarriers for pathological study and high-throughput antitumor drug screening.

•P(MVE-alt-MA)-based supramolecular hydrogels can form by inclusion complexation between cyclodextrin and adamantane.•This kind of supramolecular hydrogels is self-healing and pH-sensitive.•This kind of supramolecular hydrogels can serve as a potential platform in biomedical research.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.Self-healing pH-sensitive poly[(methyl vinyl ether)-alt-(maleic acid)]-based supramolecular hydrogels were prepared by inclusion complexation between cyclodextrin and adamantine. They may have high potential in biomedical applications.

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.