3D-Printed Tumor-on-a-Chip Model for Investigating the Effect of Matrix Stiffness on Glioblastoma Tumor Invasion

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dc.contributor.authorAmereh, Meitham
dc.contributor.authorSeyfoori, Amir
dc.contributor.authorDallinger, Briana
dc.contributor.authorAzimzadeh, Mostafa
dc.contributor.authorStefanek, Evan
dc.contributor.authorAkbari, Mohsen
dc.date.accessioned2023-10-15T13:26:26Z
dc.date.available2023-10-15T13:26:26Z
dc.date.copyright2023en_US
dc.date.issued2023
dc.description.abstractGlioblastoma multiform (GBM) tumor progression has been recognized to be correlated with extracellular matrix (ECM) stiffness. Dynamic variation of tumor ECM is primarily regulated by a family of enzymes which induce remodeling and degradation. In this paper, we investigated the effect of matrix stiffness on the invasion pattern of human glioblastoma tumoroids. A 3D-printed tumor-on-a-chip platform was utilized to culture human glioblastoma tumoroids with the capability of evaluating the effect of stiffness on tumor progression. To induce variations in the stiffness of the collagen matrix, different concentrations of collagenase were added, thereby creating an inhomogeneous collagen concentration. To better understand the mechanisms involved in GBM invasion, an in silico hybrid mathematical model was used to predict the evolution of a tumor in an inhomogeneous environment, providing the ability to study multiple dynamic interacting variables. The model consists of a continuum reaction–diffusion model for the growth of tumoroids and a discrete model to capture the migration of single cells into the surrounding tissue. Results revealed that tumoroids exhibit two distinct patterns of invasion in response to the concentration of collagenase, namely ring-type and finger-type patterns. Moreover, higher concentrations of collagenase resulted in greater invasion lengths, confirming the strong dependency of tumor behavior on the stiffness of the surrounding matrix. The agreement between the experimental results and the model’s predictions demonstrates the advantages of this approach in investigating the impact of various extracellular matrix characteristics on tumor growth and invasion.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipFunding was provided by the Natural Science and Engineering Research Council (NSERC, RGPIN-2016-04024) of Canada.en_US
dc.identifier.citationAmereh, M., Seyfoori, A., Dallinger, B., Azimzadeh, M., Stefanek, E., & Akbari, M. (2023). 3D-Printed Tumor-on-a-Chip model for investigating the effect of matrix stiffness on glioblastoma tumor invasion. Biomimetics, 8(5), 421. https://doi.org/10.3390/biomimetics8050421en_US
dc.identifier.urihttps://doi.org/10.3390/biomimetics8050421
dc.identifier.urihttp://hdl.handle.net/1828/15517
dc.language.isoenen_US
dc.publisherBiomimeticsen_US
dc.subject3D-printing
dc.subjecttumor-on-a-chip
dc.subjectglioblastoma
dc.subjectin silico model
dc.subjectLaboratory for Innovations in Micro Engineering (LiME)
dc.subjectCentre for Advanced Materials and Related Technology (CAMTEC)
dc.subject.departmentDepartment of Mechanical Engineering
dc.title3D-Printed Tumor-on-a-Chip Model for Investigating the Effect of Matrix Stiffness on Glioblastoma Tumor Invasionen_US
dc.typeArticleen_US

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