title: A double-network poly(Nɛ-acryloyl L-lysine)/hyaluronic acid hydrogel as a mimic of the breast tumor microenvironment.
abstract: To mimic the structure of breast tumor microenvironment, novel double-network poly(Nɛ-acryloyl 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.
  
  
  CONCLUSIONS
  Traditional 2D cell cultures cannot ideally represent their in vivo physiological conditions. In this work, we reported a method for preparing double-network poly(Nɛ-acryloyl 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.
authors.affiliation: State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Xu
authors.affiliation: State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China. Electronic address: jmqian@mail.xjtu.edu.cn.
authors.forename: Junmin
authors.initials: J
authors.lastname: Qian
authors.affiliation: State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: ailisuo@mail.xjtu.edu.cn.
authors.forename: Aili
authors.initials: A
authors.lastname: Suo
authors.affiliation: State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Cui
authors.affiliation: State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Jinlei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Hejing
authors.initials: H
authors.lastname: Wang
mesh_terms: D000179:Acrylates / Q000494:pharmacology*; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D063646:Carcinogenesis / Q000187:drug effects / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007700:Kinetics; D061986:MCF-7 Cells; D055595:Mechanical Phenomena; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D011107:Polylysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D000179:Acrylates; D036341:Intercellular Signaling Peptides and Proteins; C000612402:poly(Nepsilon-acryloyllysine); D011107:Polylysine; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid
keywords: Breast cancer MCF-7 cells; Double network hydrogel; Hyaluronic acid; Three-dimensional culture; Tumor model