A double-network poly(Nε-acryloyl L-lysine)/hyaluronic acid hydrogel as a mimic of the breast tumor microenvironment

To mimic the structure of breast tumor microenvironment, novel double-network poly(N-epsilon-cacryloyl L-lysine)/hyaluronic acid (pLysAAm/HA) hydrogels were fabricated by a two-step photo-polymerization process for in vitro three-dimensional (3D) cell culture. The morphology, mechanical properties, swelling and degradation behaviors of pLysAAm/HA hydrogels were investigated. The growth behavior and function of MCF-7 cells cultured on the hydrogels and standard 2D culture plates were compared. The results showed that pLysAAm/HA hydrogels had a highly porous microstructure with a double network and that their mechanical properties, swelling ratio and degradation rate depended on the degree of methacrylation of HA. The results of in vitro studies revealed that the pLysAAm/HA hydrogels could support MCF-7 cell adhesion, promote cell proliferation, and induce the diversification of cell morphologies and overexpression of VEGF, IL-8 and bFGF. The MCF-7 cells cultured on 3D hydrogels showed significantly increased migration and invasion abilities as compared to 2D-cultured cells. Preliminary in vivo results confirmed that the 3D culture of MCF-7 cells resulted in greater tumorigenesis than their 2D culture. These results indicate that the pLysAAm/HA hydrogels can provide a 3D microenvironment for MCF-7 cells that is more representative of the in vivo breast cancer. Statement of Significance Traditional 2D cell cultures cannot ideally represent their in vivo physiological conditions. In this work, we reported a method for preparing double-network poly(N-epsilon-cacryloyl L-lysine)/hyaluronic acid hydrogel, and demonstrated its suitability for use in mimicing breast tumor microenvironment. Results showed the prepared hydrogels had controllable mechanical properties, swelling ratio and degradation rate. The MCF-7 cells cultured in hydrogels expressed much higher levels of pro-angiogenic growth factors and displayed significantly enhanced migration and invasion abilities. The tumorigenic capability of MCF-7 cells pre-cultured in 3D hydrogels was enhanced significantly. Therefore, the novel hydrogel may provide a more physiologically relevant 3D in vitro model for breast cancer research. To our knowledge, this is the first report assessing a HA-based double-network hydrogel used as a tumor model. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.