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A Thermo-Sensitive Hydrogel Composed of Methylcellulose/Hyaluronic Acid/Silk Fibrin As a Biomimetic Extracellular Matrix to Simulate Breast Cancer Malignancy Publisher



Shokri R1 ; Fuenteschandia M2 ; Ai J3 ; Habibi Roudkenar M4 ; Reza Mahboubian A5 ; Rad Malekshahi M1 ; Nasser Ostad S6
Authors
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Authors Affiliations
  1. 1. Department of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Biology, Skeletal Research Center, Case Western Reserve University, Cleveland, OH, United States
  3. 3. Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical, Sciences, Tehran, Iran
  4. 4. Burn and Regenerative Medicine Research Center. Guilan University of Medical Sciences, Rasht, Iran
  5. 5. Business School, The Ingenuity Center Nottingham, University of Nottingham, United Kingdom
  6. 6. Toxicology and Poisoning Research Center, Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: European Polymer Journal Published:2022


Abstract

The development of three-dimensional (3D) culture models is promising for cancer biology studies and the discovery of new anticancer drugs because they mimic the in vivo situation better without the need for animal facilities. To reach a 3D culture matrix, we developed a temperature-sensitive hydrogel inspired by the native tumor biology approach. Hence, methylcellulose (MC), hyaluronic acid (HA), and silk fibroin (SF) were combined to mimic the native extracellular matrix. The obtained MCHASF hydrogel was physicochemically characterized and exhibited a similar stiffness to native breast tumors, showing in vitro stability for up to 6 weeks, a non-homogeneous surface, and high pore interconnectivity characters. Human breast cancer cells (MDA-MB-231) cultured in hydrogel were morphologically assessed and showed irregular cytoskeleton shapes and actin-based protrusions characteristic of their malignancy. In addition, the cells displayed a higher cell migration rate and up-regulated expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP2, MMP9) and resistance to chemotherapy than two-dimensional (2D) cultures, which demonstrates this 3D environment enhanced metastatic potential. Overall, this novel 3D in vitro model can offer an insight into investigating different features of tumor cell behavior, including metastasis and drug response. © 2022
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