• Effect of the Molecular Structure of TPU on the Cellular Structure of Nanocellular Polymers Based on PMMA/TPU Blends

      Sánchez-Calderón, Ismael; orcid: 0000-0003-3367-8371; email: ismaelsc@fmc.uva.es; Bernardo, Victoria; email: v.bernardo@cellmattechnologies.com; Santiago-Calvo, Mercedes; orcid: 0000-0001-7678-5746; email: mercesc@fmc.uva.es; Naji, Haneen; email: haneen.naji@postgrad.manchester.ac.uk; Saiani, Alberto; email: a.saiani@manchester.ac.uk; Rodríguez-Pérez, Miguel Ángel; orcid: 0000-0002-3607-690X; email: marrod@fmc.uva.es (MDPI, 2021-09-10)
      In this work, the effects of thermoplastic polyurethane (TPU) chemistry and concentration on the cellular structure of nanocellular polymers based on poly(methyl-methacrylate) (PMMA) are presented. Three grades of TPU with different fractions of hard segments (HS) (60%, 70%, and 80%) have been synthesized by the prepolymer method. Nanocellular polymers based on PMMA have been produced by gas dissolution foaming using TPU as a nucleating agent in different contents (0.5 wt%, 2 wt%, and 5 wt%). TPU characterization shows that as the content of HS increases, the density, hardness, and molecular weight of the TPU are higher. PMMA/TPU cellular materials show a gradient cell size distribution from the edge of the sample towards the nanocellular core. In the core region, the addition of TPU has a strong nucleating effect in PMMA. Core structure depends on the HS content and the TPU content. As the HS or TPU content increases, the cell nucleation density increases, and the cell size is reduced. Then, the use of TPUs with different characteristics allows controlling the cellular structure. Nanocellular polymers have been obtained with a core relative density between 0.15 and 0.20 and cell sizes between 220 and 640 nm.
    • Neutrally charged self-assembling peptide hydrogel recapitulates in vitro mechanisms of breast cancer progression.

      Clough, Helen C; email: helen.clough@manchester.ac.uk; O'Brien, Marie; email: marie.obrien@manchester.ac.uk; Zhu, Xinyi; email: xinyi.zhu@manchester.ac.uk; Miller, Aline F; email: a.miller@manchesterbiogel.com; Saiani, Alberto; email: a.saiani@manchester.ac.uk; Tsigkou, Olga; email: olga.tsigkou@manchester.ac.uk (2021-05-21)
      Self-assembling peptide hydrogels (SAPH) are a popular biomaterial due to their biocompatibility with a wide range of cell types, synthetic design, structural properties that provide a more accurate 3D microenvironment, and potential for cell- and/or drug-delivery system. Mimicking solid tumors in vitro using hydrogels is one method of testing anti-cancer drug efficacy and observing cancerous cell-ECM interactions within a 3D system. In this study, a SAPH, PeptiGel®Alpha1, was used to model in vitro the 3D breast tumor microenvironment. PeptiGel®Alpha1 is composed of entangled nanofibers with consistent diameter and mechanical properties similar to breast cancer that more accurately mimic the stiffness of breast tumor tissue than Matrigel® or collagen type I. PeptiGel®Alpha1 supported the viability and growth of the breast cancer cell lines MCF-7 and MDA-MB-231 and recapitulated key features of solid tumors such as hypoxia and invasion. MCF-7 cells in the hydrogels formed large spheroids resembling acini, while MDA-MB-231 remained dispersed. When treated with tamoxifen, PeptiGel®Alpha1 acted as a barrier, providing drug penetration geometry similar to that in vivo, providing better prediction of the drug effect. Finally, it was observed that MCF-7 cells engulfed the peptide matrix after 14 days, highlighting a potential use in drug delivery. PeptiGel®Alpha1 is a suitable platform for in vitro modeling of breast cancer. [Abstract copyright: Copyright © 2021. Published by Elsevier B.V.]
    • Self-Assembling Polypeptide Hydrogels as a Platform to Recapitulate the Tumor Microenvironment

      Lachowski, Dariusz; orcid: 0000-0003-1194-8019; email: d.lachowski15@imperial.ac.uk; Matellan, Carlos; orcid: 0000-0002-3589-6252; email: c.matellan16@imperial.ac.uk; Cortes, Ernesto; orcid: 0000-0001-6106-1323; email: j.e.corteslopez@imperial.ac.uk; Saiani, Alberto; email: a.saiani@manchester.ac.uk; Miller, Aline F.; email: a.miller@manchesterbiogel.com; del Río Hernández, Armando E.; orcid: 0000-0001-5062-8910; email: a.del-rio-hernandez@imperial.ac.uk (MDPI, 2021-06-30)
      The tumor microenvironment plays a critical role in modulating cancer cell migration, metabolism, and malignancy, thus, highlighting the need to develop in vitro culture systems that can recapitulate its abnormal properties. While a variety of stiffness-tunable biomaterials, reviewed here, have been developed to mimic the rigidity of the tumor extracellular matrix, culture systems that can recapitulate the broader extracellular context of the tumor microenvironment (including pH and temperature) remain comparably unexplored, partially due to the difficulty in independently tuning these parameters. Here, we investigate a self-assembled polypeptide network hydrogel as a cell culture platform and demonstrate that the culture parameters, including the substrate stiffness, extracellular pH and temperature, can be independently controlled. We then use this biomaterial as a cell culture substrate to assess the effect of stiffness, pH and temperature on Suit2 cells, a pancreatic cancer cell line, and demonstrate that these microenvironmental factors can regulate two critical transcription factors in cancer: yes-associated protein 1 (YAP) and hypoxia inducible factor (HIF-1A).