Semi-Synthetic Click-Gelatin Hydrogels as Tunable Platforms for 3D Cancer Cell Culture
Luke Hipwood,
Julien Clegg,
Angus Weekes,
Jordan W. Davern,
Tim R. Dargaville,
Christoph Meinert,
Nathalie Bock
Affiliations
Luke Hipwood
Faculty of Health, School of Biomedical Sciences, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia
Julien Clegg
Centre for Biomedical Technologies, Science and Engineering Faculty, School of Mechanical, Medical and Process Engineering, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia
Angus Weekes
Centre for Biomedical Technologies, Science and Engineering Faculty, School of Mechanical, Medical and Process Engineering, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia
Jordan W. Davern
Centre for Biomedical Technologies, Science and Engineering Faculty, School of Mechanical, Medical and Process Engineering, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia
Tim R. Dargaville
Centre for Materials Science, Faculty of Science, School of Chemistry and Physics, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia
Christoph Meinert
Centre for Biomedical Technologies, Science and Engineering Faculty, School of Mechanical, Medical and Process Engineering, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia
Nathalie Bock
Faculty of Health, School of Biomedical Sciences, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia
Basement membrane extracts (BME) derived from Engelbreth–Holm–Swarm (EHS) mouse sarcomas such as Matrigel® remain the gold standard extracellular matrix (ECM) for three-dimensional (3D) cell culture in cancer research. Yet, BMEs suffer from substantial batch-to-batch variation, ill-defined composition, and lack the ability for physichochemical manipulation. Here, we developed a novel 3D cell culture system based on thiolated gelatin (Gel-SH), an inexpensive and highly controlled raw material capable of forming hydrogels with a high level of biophysical control and cell-instructive bioactivity. We demonstrate the successful thiolation of gelatin raw materials to enable rapid covalent crosslinking upon mixing with a synthetic poly(ethylene glycol) (PEG)-based crosslinker. The mechanical properties of the resulting gelatin-based hydrogels were readily tuned by varying precursor material concentrations, with Young’s moduli ranging from ~2.5 to 5.8 kPa. All hydrogels of varying stiffnesses supported the viability and proliferation of MDA-MB-231 and MCF-7 breast cancer cell lines for 14 and 21 days of cell culture, respectively. Additionally, the gelatin-based hydrogels supported the growth, viability, and osteogenic differentiation of patient-derived preosteoblasts over 28 days of culture. Collectively, our data demonstrate that gelatin-based biomaterials provide an inexpensive and tunable 3D cell culture platform that may overcome the limitations of traditional BMEs.
