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Semi-Synthetic Click-Gelatin Hydrogels as Tunable Platforms for 3D Cancer Cell Culture
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 composi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778549/ https://www.ncbi.nlm.nih.gov/pubmed/36547345 http://dx.doi.org/10.3390/gels8120821 |
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author | Hipwood, Luke Clegg, Julien Weekes, Angus Davern, Jordan W. Dargaville, Tim R. Meinert, Christoph Bock, Nathalie |
author_facet | Hipwood, Luke Clegg, Julien Weekes, Angus Davern, Jordan W. Dargaville, Tim R. Meinert, Christoph Bock, Nathalie |
author_sort | Hipwood, Luke |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9778549 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97785492022-12-23 Semi-Synthetic Click-Gelatin Hydrogels as Tunable Platforms for 3D Cancer Cell Culture Hipwood, Luke Clegg, Julien Weekes, Angus Davern, Jordan W. Dargaville, Tim R. Meinert, Christoph Bock, Nathalie Gels Article 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. MDPI 2022-12-12 /pmc/articles/PMC9778549/ /pubmed/36547345 http://dx.doi.org/10.3390/gels8120821 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hipwood, Luke Clegg, Julien Weekes, Angus Davern, Jordan W. Dargaville, Tim R. Meinert, Christoph Bock, Nathalie Semi-Synthetic Click-Gelatin Hydrogels as Tunable Platforms for 3D Cancer Cell Culture |
title | Semi-Synthetic Click-Gelatin Hydrogels as Tunable Platforms for 3D Cancer Cell Culture |
title_full | Semi-Synthetic Click-Gelatin Hydrogels as Tunable Platforms for 3D Cancer Cell Culture |
title_fullStr | Semi-Synthetic Click-Gelatin Hydrogels as Tunable Platforms for 3D Cancer Cell Culture |
title_full_unstemmed | Semi-Synthetic Click-Gelatin Hydrogels as Tunable Platforms for 3D Cancer Cell Culture |
title_short | Semi-Synthetic Click-Gelatin Hydrogels as Tunable Platforms for 3D Cancer Cell Culture |
title_sort | semi-synthetic click-gelatin hydrogels as tunable platforms for 3d cancer cell culture |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778549/ https://www.ncbi.nlm.nih.gov/pubmed/36547345 http://dx.doi.org/10.3390/gels8120821 |
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