GelMA, click-chemistry gelatin and bioprinted polyethylene glycol-based hydrogels as 3D ex vivo drug testing platforms for patient-derived breast cancer organoids

Nathalie Bock; Farzaneh Forouz; Luke Hipwood; Julien Clegg; Penny Jeffery; Madeline Gough; Tirsa van Wyngaard; Christopher Pyke; Mark N. Adams; Laura J. Bray; Laura Croft; Erik W. Thompson; Thomas Kryza; Christoph Meinert

doi:10.3390/pharmaceutics15010261

GelMA, click-chemistry gelatin and bioprinted polyethylene glycol-based hydrogels as 3D ex vivo drug testing platforms for patient-derived breast cancer organoids

Nathalie Bock
, Farzaneh Forouz
, Luke Hipwood
, Julien Clegg
, Penny Jeffery
, Madeline Gough
, Tirsa van Wyngaard
, Christopher Pyke
, Mark N. Adams
, Laura J. Bray
, Laura Croft
, Erik W. Thompson
, Thomas Kryza
, Christoph Meinert

Research output: Contribution to journal › Article › Research › peer-review

62 Citations (Scopus)

Abstract

3D organoid model technologies have led to the development of innovative tools for cancer precision medicine. Yet, the gold standard culture system (Matrigel^®) lacks the ability for extensive biophysical manipulation needed to model various cancer microenvironments and has inherent batch-to-batch variability. Tunable hydrogel matrices provide enhanced capability for drug testing in breast cancer (BCa), by better mimicking key physicochemical characteristics of this disease’s extracellular matrix. Here, we encapsulated patient-derived breast cancer cells in bioprinted polyethylene glycol-derived hydrogels (PEG), functionalized with adhesion peptides (RGD, GFOGER and DYIGSR) and gelatin-derived hydrogels (gelatin methacryloyl; GelMA and thiolated-gelatin crosslinked with PEG-4MAL; GelSH). Within ranges of BCa stiffnesses (1–6 kPa), GelMA, GelSH and PEG-based hydrogels successfully supported the growth and organoid formation of HR+,−/HER2+,− primary cancer cells for at least 2–3 weeks, with superior organoid formation within the GelSH biomaterial (up to 268% growth after 15 days). BCa organoids responded to doxorubicin, EP31670 and paclitaxel treatments with increased IC₅₀ concentrations on organoids compared to 2D cultures, and highest IC₅₀ for organoids in GelSH. Cell viability after doxorubicin treatment (1 µM) remained >2-fold higher in the 3D gels compared to 2D and doxorubicin/paclitaxel (both 5 µM) were ~2.75–3-fold less potent in GelSH compared to PEG hydrogels. The data demonstrate the potential of hydrogel matrices as easy-to-use and effective preclinical tools for therapy assessment in patient-derived breast cancer organoids.

Original language	English
Article number	261
Number of pages	23
Journal	Pharmaceutics
Volume	15
Issue number	1
DOIs	https://doi.org/10.3390/pharmaceutics15010261
Publication status	Published - 12 Jan 2023
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

3D cancer model
adriamycin
breast cancer
doxorubicin
drug resistance
EP31670
extracellular matrix
gelatin
GelMA
hydrogel
paclitaxel
patient-derived organoid
polyethylene glycol
precision medicine
tumor microenvironment

Access to Document

10.3390/pharmaceutics15010261

Cite this

Bock, N., Forouz, F., Hipwood, L., Clegg, J., Jeffery, P., Gough, M., van Wyngaard, T., Pyke, C., Adams, M. N., Bray, L. J., Croft, L., Thompson, E. W., Kryza, T., & Meinert, C. (2023). GelMA, click-chemistry gelatin and bioprinted polyethylene glycol-based hydrogels as 3D ex vivo drug testing platforms for patient-derived breast cancer organoids. Pharmaceutics, 15(1), Article 261. https://doi.org/10.3390/pharmaceutics15010261

@article{568cb83ca52a41f0a9c65dfa6c3f7760,

title = "GelMA, click-chemistry gelatin and bioprinted polyethylene glycol-based hydrogels as 3D ex vivo drug testing platforms for patient-derived breast cancer organoids",

abstract = "3D organoid model technologies have led to the development of innovative tools for cancer precision medicine. Yet, the gold standard culture system (Matrigel{\textregistered}) lacks the ability for extensive biophysical manipulation needed to model various cancer microenvironments and has inherent batch-to-batch variability. Tunable hydrogel matrices provide enhanced capability for drug testing in breast cancer (BCa), by better mimicking key physicochemical characteristics of this disease{\textquoteright}s extracellular matrix. Here, we encapsulated patient-derived breast cancer cells in bioprinted polyethylene glycol-derived hydrogels (PEG), functionalized with adhesion peptides (RGD, GFOGER and DYIGSR) and gelatin-derived hydrogels (gelatin methacryloyl; GelMA and thiolated-gelatin crosslinked with PEG-4MAL; GelSH). Within ranges of BCa stiffnesses (1–6 kPa), GelMA, GelSH and PEG-based hydrogels successfully supported the growth and organoid formation of HR+,−/HER2+,− primary cancer cells for at least 2–3 weeks, with superior organoid formation within the GelSH biomaterial (up to 268\% growth after 15 days). BCa organoids responded to doxorubicin, EP31670 and paclitaxel treatments with increased IC50 concentrations on organoids compared to 2D cultures, and highest IC50 for organoids in GelSH. Cell viability after doxorubicin treatment (1 µM) remained >2-fold higher in the 3D gels compared to 2D and doxorubicin/paclitaxel (both 5 µM) were \textasciitilde{}2.75–3-fold less potent in GelSH compared to PEG hydrogels. The data demonstrate the potential of hydrogel matrices as easy-to-use and effective preclinical tools for therapy assessment in patient-derived breast cancer organoids.",

keywords = "3D cancer model, adriamycin, breast cancer, doxorubicin, drug resistance, EP31670, extracellular matrix, gelatin, GelMA, hydrogel, paclitaxel, patient-derived organoid, polyethylene glycol, precision medicine, tumor microenvironment",

author = "Nathalie Bock and Farzaneh Forouz and Luke Hipwood and Julien Clegg and Penny Jeffery and Madeline Gough and \{van Wyngaard\}, Tirsa and Christopher Pyke and Adams, \{Mark N.\} and Bray, \{Laura J.\} and Laura Croft and Thompson, \{Erik W.\} and Thomas Kryza and Christoph Meinert",

note = "Funding Information: N.B. acknowledges support from the Advanced Queensland Industry Research Fellowship (AQIRF066-2019RD2), from JJ Richards \& Sons, and from the Max Planck Queensland Centre for the Materials Science of Extracellular Matrices. This work was supported in part by the Medical Research Future Fund (MRFF) Rapid Applied Research Translation Program (Centre for Personalised Analysis of Cancers; CPAC: GA59729) awarded to E.W.T. The Mater-QUT Breast Cancer Research Biobank is co-funded by Mater Research and QUT. The Translational Research Institute receives support from the Australian Government. Publisher Copyright: {\textcopyright} 2023 by the authors.",

year = "2023",

month = jan,

day = "12",

doi = "10.3390/pharmaceutics15010261",

language = "English",

volume = "15",

journal = "Pharmaceutics",

issn = "1999-4923",

publisher = "MDPI AG",

number = "1",

}

Bock, N, Forouz, F, Hipwood, L, Clegg, J, Jeffery, P, Gough, M, van Wyngaard, T, Pyke, C, Adams, MN, Bray, LJ, Croft, L, Thompson, EW, Kryza, T & Meinert, C 2023, 'GelMA, click-chemistry gelatin and bioprinted polyethylene glycol-based hydrogels as 3D ex vivo drug testing platforms for patient-derived breast cancer organoids', Pharmaceutics, vol. 15, no. 1, 261. https://doi.org/10.3390/pharmaceutics15010261

TY - JOUR

T1 - GelMA, click-chemistry gelatin and bioprinted polyethylene glycol-based hydrogels as 3D ex vivo drug testing platforms for patient-derived breast cancer organoids

AU - Bock, Nathalie

AU - Forouz, Farzaneh

AU - Hipwood, Luke

AU - Clegg, Julien

AU - Jeffery, Penny

AU - Gough, Madeline

AU - van Wyngaard, Tirsa

AU - Pyke, Christopher

AU - Adams, Mark N.

AU - Bray, Laura J.

AU - Croft, Laura

AU - Thompson, Erik W.

AU - Kryza, Thomas

AU - Meinert, Christoph

N1 - Funding Information: N.B. acknowledges support from the Advanced Queensland Industry Research Fellowship (AQIRF066-2019RD2), from JJ Richards & Sons, and from the Max Planck Queensland Centre for the Materials Science of Extracellular Matrices. This work was supported in part by the Medical Research Future Fund (MRFF) Rapid Applied Research Translation Program (Centre for Personalised Analysis of Cancers; CPAC: GA59729) awarded to E.W.T. The Mater-QUT Breast Cancer Research Biobank is co-funded by Mater Research and QUT. The Translational Research Institute receives support from the Australian Government. Publisher Copyright: © 2023 by the authors.

PY - 2023/1/12

Y1 - 2023/1/12

N2 - 3D organoid model technologies have led to the development of innovative tools for cancer precision medicine. Yet, the gold standard culture system (Matrigel®) lacks the ability for extensive biophysical manipulation needed to model various cancer microenvironments and has inherent batch-to-batch variability. Tunable hydrogel matrices provide enhanced capability for drug testing in breast cancer (BCa), by better mimicking key physicochemical characteristics of this disease’s extracellular matrix. Here, we encapsulated patient-derived breast cancer cells in bioprinted polyethylene glycol-derived hydrogels (PEG), functionalized with adhesion peptides (RGD, GFOGER and DYIGSR) and gelatin-derived hydrogels (gelatin methacryloyl; GelMA and thiolated-gelatin crosslinked with PEG-4MAL; GelSH). Within ranges of BCa stiffnesses (1–6 kPa), GelMA, GelSH and PEG-based hydrogels successfully supported the growth and organoid formation of HR+,−/HER2+,− primary cancer cells for at least 2–3 weeks, with superior organoid formation within the GelSH biomaterial (up to 268% growth after 15 days). BCa organoids responded to doxorubicin, EP31670 and paclitaxel treatments with increased IC50 concentrations on organoids compared to 2D cultures, and highest IC50 for organoids in GelSH. Cell viability after doxorubicin treatment (1 µM) remained >2-fold higher in the 3D gels compared to 2D and doxorubicin/paclitaxel (both 5 µM) were ~2.75–3-fold less potent in GelSH compared to PEG hydrogels. The data demonstrate the potential of hydrogel matrices as easy-to-use and effective preclinical tools for therapy assessment in patient-derived breast cancer organoids.

AB - 3D organoid model technologies have led to the development of innovative tools for cancer precision medicine. Yet, the gold standard culture system (Matrigel®) lacks the ability for extensive biophysical manipulation needed to model various cancer microenvironments and has inherent batch-to-batch variability. Tunable hydrogel matrices provide enhanced capability for drug testing in breast cancer (BCa), by better mimicking key physicochemical characteristics of this disease’s extracellular matrix. Here, we encapsulated patient-derived breast cancer cells in bioprinted polyethylene glycol-derived hydrogels (PEG), functionalized with adhesion peptides (RGD, GFOGER and DYIGSR) and gelatin-derived hydrogels (gelatin methacryloyl; GelMA and thiolated-gelatin crosslinked with PEG-4MAL; GelSH). Within ranges of BCa stiffnesses (1–6 kPa), GelMA, GelSH and PEG-based hydrogels successfully supported the growth and organoid formation of HR+,−/HER2+,− primary cancer cells for at least 2–3 weeks, with superior organoid formation within the GelSH biomaterial (up to 268% growth after 15 days). BCa organoids responded to doxorubicin, EP31670 and paclitaxel treatments with increased IC50 concentrations on organoids compared to 2D cultures, and highest IC50 for organoids in GelSH. Cell viability after doxorubicin treatment (1 µM) remained >2-fold higher in the 3D gels compared to 2D and doxorubicin/paclitaxel (both 5 µM) were ~2.75–3-fold less potent in GelSH compared to PEG hydrogels. The data demonstrate the potential of hydrogel matrices as easy-to-use and effective preclinical tools for therapy assessment in patient-derived breast cancer organoids.

KW - 3D cancer model

KW - adriamycin

KW - breast cancer

KW - doxorubicin

KW - drug resistance

KW - EP31670

KW - extracellular matrix

KW - gelatin

KW - GelMA

KW - hydrogel

KW - paclitaxel

KW - patient-derived organoid

KW - polyethylene glycol

KW - precision medicine

KW - tumor microenvironment

UR - https://www.scopus.com/pages/publications/85146784281

U2 - 10.3390/pharmaceutics15010261

DO - 10.3390/pharmaceutics15010261

M3 - Article

AN - SCOPUS:85146784281

SN - 1999-4923

VL - 15

JO - Pharmaceutics

JF - Pharmaceutics

IS - 1

M1 - 261

ER -

GelMA, click-chemistry gelatin and bioprinted polyethylene glycol-based hydrogels as 3D ex vivo drug testing platforms for patient-derived breast cancer organoids

Abstract

UN SDGs

Keywords

Access to Document

Other files and links

ARC Training Centre for Cell and Tissue Engineering Technologies

Cite this

GelMA, click-chemistry gelatin and bioprinted polyethylene glycol-based hydrogels as 3D ex vivo drug testing platforms for patient-derived breast cancer organoids

Abstract

UN SDGs

Keywords

Access to Document

Other files and links

Projects

ARC Training Centre for Cell and Tissue Engineering Technologies

Cite this