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Cancers
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Bioengineering and Cancer
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Bioengineering and Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 17393

Special Issue Editor

Dr. Daniela Loessner

E-Mail Website
Guest Editor
1. Department of Chemical Engineering and Department of Materials Science and Engineering, Faculty of Engineering, Monash University, Melbourne, VIC 3800, Australia
2. Department of Anatomy and Developmental Biology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC 3800, Australia
Interests: tissue engineering; biomaterials; tumour microenvironment; cell and matrix biology; 3D cancer models

Special Issue Information

Dear Colleagues,

Biomimetic tissue-engineered technologies have produced contemporary tools for research into cancer. Biomaterial-based 3D cancer models harbor the dimensionality and biochemical and mechanical properties of tumor tissues. Although biomaterials mimic the architecture and composition of tumor-associated extracellular matrices and cell functions as seen in patient tumors, to date, only a minority of 3D cancer cell cultures are based on these instructive materials. This is likely caused by the level of complexity and difficulty of using these models, as well as the limited or cumbersome analytical techniques and validation. However, there is an increasing dialog between life scientists and engineers. Most 3D approaches utilize reconstituted matrices that originate from murine tumors, containing murine proteins in undefined amounts, or rat-derived collagen. Novel 3D models require complementary and multi-disciplinary partnerships in tumor biology, physical sciences, and additive manufacturing. This Special Issue will highlight applications and challenges of tissue-engineered platforms, including multi-component and 3D-bioprinted approaches, such as 3D tumor and metastasis models.

Dr. Daniela Loessner
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • tissue engineering
  • tumour biology
  • biomechanics
  • functional materials
  • extracellular matrix
  • hydrogels
  • scaffolds
  • 3D bioprinting
  • cancer cells
  • metastasis

Published Papers (4 papers)

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Research

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26 pages, 3350 KiB  
Article
Stromal Cells Promote Matrix Deposition, Remodelling and an Immunosuppressive Tumour Microenvironment in a 3D Model of Colon Cancer
by Niamh A. Leonard, Eileen Reidy, Kerry Thompson, Emma McDermott, Eleonora Peerani, Elena Tomas Bort, Frances R. Balkwill, Daniela Loessner and Aideen E. Ryan
Cancers 2021, 13(23), 5998; https://doi.org/10.3390/cancers13235998 - 29 Nov 2021
Cited by 7 | Viewed by 3684
Abstract
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. CRC develops in a complex tumour microenvironment (TME) with both mesenchymal stromal cells (MSCs) and immune infiltrate, shown to alter disease progression and treatment response. We hypothesised that an accessible, affordable [...] Read more.
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. CRC develops in a complex tumour microenvironment (TME) with both mesenchymal stromal cells (MSCs) and immune infiltrate, shown to alter disease progression and treatment response. We hypothesised that an accessible, affordable model of CRC that combines multiple cell types will improve research translation to the clinic and enable the identification of novel therapeutic targets. A viable gelatine-methacrloyl-based hydrogel culture system that incorporates CRC cells with MSCs and a monocyte cell line was developed. Gels were analysed on day 10 by PCR, cytokine array, microscopy and flow cytometry. The addition of stromal cells increased transcription of matrix remodelling proteins FN1 and MMP9, induced release of tumour-promoting immune molecules MIF, Serpin E1, CXCL1, IL-8 and CXCL12 and altered cancer cell expression of immunotherapeutic targets EGFR, CD47 and PD-L1. Treatment with PD153035, an EGFR inhibitor, revealed altered CRC expression of PD-L1 but only in gels lacking MSCs. We established a viable 3D model of CRC that combined cancer cells, MSCs and monocytic cells that can be used to research the role the stroma plays in the TME, identify novel therapeutic targets and improve the transitional efficacy of therapies. Full article
(This article belongs to the Special Issue Bioengineering and Cancer)
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20 pages, 3869 KiB  
Article
Mapping Tumor Spheroid Mechanics in Dependence of 3D Microenvironment Stiffness and Degradability by Brillouin Microscopy
by Vaibhav Mahajan, Timon Beck, Paulina Gregorczyk, André Ruland, Simon Alberti, Jochen Guck, Carsten Werner, Raimund Schlüßler and Anna Verena Taubenberger
Cancers 2021, 13(21), 5549; https://doi.org/10.3390/cancers13215549 - 5 Nov 2021
Cited by 24 | Viewed by 5339
Abstract
Altered biophysical properties of cancer cells and of their microenvironment contribute to cancer progression. While the relationship between microenvironmental stiffness and cancer cell mechanical properties and responses has been previously studied using two-dimensional (2D) systems, much less is known about it in a [...] Read more.
Altered biophysical properties of cancer cells and of their microenvironment contribute to cancer progression. While the relationship between microenvironmental stiffness and cancer cell mechanical properties and responses has been previously studied using two-dimensional (2D) systems, much less is known about it in a physiologically more relevant 3D context and in particular for multicellular systems. To investigate the influence of microenvironment stiffness on tumor spheroid mechanics, we first generated MCF-7 tumor spheroids within matrix metalloproteinase (MMP)-degradable 3D polyethylene glycol (PEG)-heparin hydrogels, where spheroids showed reduced growth in stiffer hydrogels. We then quantitatively mapped the mechanical properties of tumor spheroids in situ using Brillouin microscopy. Maps acquired for tumor spheroids grown within stiff hydrogels showed elevated Brillouin frequency shifts (hence increased longitudinal elastic moduli) with increasing hydrogel stiffness. Maps furthermore revealed spatial variations of the mechanical properties across the spheroids’ cross-sections. When hydrogel degradability was blocked, comparable Brillouin frequency shifts of the MCF-7 spheroids were found in both compliant and stiff hydrogels, along with similar levels of growth-induced compressive stress. Under low compressive stress, single cells or free multicellular aggregates showed consistently lower Brillouin frequency shifts compared to spheroids growing within hydrogels. Thus, the spheroids’ mechanical properties were modulated by matrix stiffness and degradability as well as multicellularity, and also to the associated level of compressive stress felt by tumor spheroids. Spheroids generated from a panel of invasive breast, prostate and pancreatic cancer cell lines within degradable stiff hydrogels, showed higher Brillouin frequency shifts and less cell invasion compared to those in compliant hydrogels. Taken together, our findings contribute to a better understanding of the interplay between cancer cells and microenvironment mechanics and degradability, which is relevant to better understand cancer progression. Full article
(This article belongs to the Special Issue Bioengineering and Cancer)
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Review

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31 pages, 4959 KiB  
Review
Modeling the Tumor Microenvironment of Ovarian Cancer: The Application of Self-Assembling Biomaterials
by Ana Karen Mendoza-Martinez, Daniela Loessner, Alvaro Mata and Helena S. Azevedo
Cancers 2021, 13(22), 5745; https://doi.org/10.3390/cancers13225745 - 16 Nov 2021
Cited by 6 | Viewed by 3995
Abstract
Ovarian cancer (OvCa) is one of the leading causes of gynecologic malignancies. Despite treatment with surgery and chemotherapy, OvCa disseminates and recurs frequently, reducing the survival rate for patients. There is an urgent need to develop more effective treatment options for women diagnosed [...] Read more.
Ovarian cancer (OvCa) is one of the leading causes of gynecologic malignancies. Despite treatment with surgery and chemotherapy, OvCa disseminates and recurs frequently, reducing the survival rate for patients. There is an urgent need to develop more effective treatment options for women diagnosed with OvCa. The tumor microenvironment (TME) is a key driver of disease progression, metastasis and resistance to treatment. For this reason, 3D models have been designed to represent this specific niche and allow more realistic cell behaviors compared to conventional 2D approaches. In particular, self-assembling peptides represent a promising biomaterial platform to study tumor biology. They form nanofiber networks that resemble the architecture of the extracellular matrix and can be designed to display mechanical properties and biochemical motifs representative of the TME. In this review, we highlight the properties and benefits of emerging 3D platforms used to model the ovarian TME. We also outline the challenges associated with using these 3D systems and provide suggestions for future studies and developments. We conclude that our understanding of OvCa and advances in materials science will progress the engineering of novel 3D approaches, which will enable the development of more effective therapies. Full article
(This article belongs to the Special Issue Bioengineering and Cancer)
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20 pages, 6804 KiB  
Review
3D Breast Tumor Models for Radiobiology Applications
by Akhilandeshwari Ravichandran, Julien Clegg, Mark N. Adams, Madison Hampson, Andrew Fielding and Laura J. Bray
Cancers 2021, 13(22), 5714; https://doi.org/10.3390/cancers13225714 - 15 Nov 2021
Cited by 5 | Viewed by 2795
Abstract
Breast cancer is a leading cause of cancer-associated death in women. The clinical management of breast cancers is normally carried out using a combination of chemotherapy, surgery and radiation therapy. The majority of research investigating breast cancer therapy until now has mainly utilized [...] Read more.
Breast cancer is a leading cause of cancer-associated death in women. The clinical management of breast cancers is normally carried out using a combination of chemotherapy, surgery and radiation therapy. The majority of research investigating breast cancer therapy until now has mainly utilized two-dimensional (2D) in vitro cultures or murine models of disease. However, there has been significant uptake of three-dimensional (3D) in vitro models by cancer researchers over the past decade, highlighting a complimentary model for studies of radiotherapy, especially in conjunction with chemotherapy. In this review, we underline the effects of radiation therapy on normal and malignant breast cells and tissues, and explore the emerging opportunities that pre-clinical 3D models offer in improving our understanding of this treatment modality. Full article
(This article belongs to the Special Issue Bioengineering and Cancer)
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