3D Collagen-Nanocellulose Matrices Model the Tumour Microenvironment of Pancreatic Cancer

Rodrigo Curvello; Verena Kast; Mohammed H Abuwarwar; Anne L Fletcher; Gil Garnier; Daniela Loessner

doi:10.3389/fdgth.2021.704584

3D Collagen-Nanocellulose Matrices Model the Tumour Microenvironment of Pancreatic Cancer

Front Digit Health. 2021 Jul 26:3:704584. doi: 10.3389/fdgth.2021.704584. eCollection 2021.

Authors

Rodrigo Curvello¹, Verena Kast², Mohammed H Abuwarwar³, Anne L Fletcher³, Gil Garnier^{1

4}, Daniela Loessner^{1

5

6}

Affiliations

¹ Department of Chemical Engineering, Faculty of Engineering, Monash University, Clayton, VIC, Australia.
² Max Bergmann Center of Biomaterials Dresden, Leibniz Institute of Polymer Research Dresden E.V., Dresden, Germany.
³ Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
⁴ Department of Chemical Engineering, Bioresource Processing Research Institute of Australia (BioPRIA), Monash University, Clayton, VIC, Australia.
⁵ Department of Materials Science and Engineering, Faculty of Engineering, Monash University, Clayton, VIC, Australia.
⁶ Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Science, Monash University, Clayton, VIC, Australia.

Abstract

Three-dimensional (3D) cancer models are invaluable tools designed to study tumour biology and new treatments. Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest types of cancer, has been progressively explored with bioengineered 3D approaches by deconstructing elements of its tumour microenvironment. Here, we investigated the suitability of collagen-nanocellulose hydrogels to mimic the extracellular matrix of PDAC and to promote the formation of tumour spheroids and multicellular 3D cultures with stromal cells. Blending of type I collagen fibrils and cellulose nanofibres formed a matrix of controllable stiffness, which resembled the lower profile of pancreatic tumour tissues. Collagen-nanocellulose hydrogels supported the growth of tumour spheroids and multicellular 3D cultures, with increased metabolic activity and matrix stiffness. To validate our 3D cancer model, we tested the individual and combined effects of the anti-cancer compound triptolide and the chemotherapeutics gemcitabine and paclitaxel, resulting in differential cell responses. Our blended 3D matrices with tuneable mechanical properties consistently maintain the growth of PDAC cells and its cellular microenvironment and allow the screening of anti-cancer treatments.

Keywords: collagen; extracellular matrix; hydrogels; nanocellulose; pancreatic cancer; stiffness.