An open-source technology platform to increase reproducibility and enable high-throughput production of tailorable gelatin methacryloyl (GelMA) - based hydrogels

Gelatin methacryloyl (GelMA)-based hydrogels have become highly studied as modular tissue culture platforms due to the combination of the bioactivity of gelatin and tailorability of photo-crosslinkable hydrogels. However, current production and characterization workflows still rely on manual, time-c...

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Main Authors: Sebastian Eggert, Melanie Kahl, Nathalie Bock, Christoph Meinert, Oliver Friedrich, Dietmar W. Hutmacher
Format: Article
Language:English
Published: Elsevier 2021-06-01
Series:Materials & Design
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0264127521001726
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author Sebastian Eggert
Melanie Kahl
Nathalie Bock
Christoph Meinert
Oliver Friedrich
Dietmar W. Hutmacher
author_facet Sebastian Eggert
Melanie Kahl
Nathalie Bock
Christoph Meinert
Oliver Friedrich
Dietmar W. Hutmacher
author_sort Sebastian Eggert
collection DOAJ
description Gelatin methacryloyl (GelMA)-based hydrogels have become highly studied as modular tissue culture platforms due to the combination of the bioactivity of gelatin and tailorability of photo-crosslinkable hydrogels. However, current production and characterization workflows still rely on manual, time-consuming, and low-throughput processes, ultimately limiting widespread adaption. To address these challenges, an open-source technology platform is engineered and validated for automated high-throughput production of GelMA-based 3D constructs by integrating automated pipetting capabilities for viscous and non-viscous liquids. Firstly, the platform is applied in combination with inexpensive absorbance measurements to systematically optimize the mixing sequence for GelMA-based precursor solutions. This enables a decrease in the relative standard deviation of the prepared mixtures from 63% to 2.5%, demonstrating a significantly improved reproducibility. Next, the applicability and high-throughput capacity are demonstrated by the reproducible generation of GelMA dilution series with 0.5 and 2% (w/v) concentration steps as well as double network hydrogels consisting of 2% (w/v) alginate and 5% (w/v) GelMA. Finally, a simple and user-friendly methodology is described that integrates Design of Experiments approaches to systematically study the combinatorial effects of material and crosslinking parameters and to establish a parameter library for on-demand production of mechanically defined GelMA-based hydrogels. The platform enables reproducible production and offers an open-source and accessible alternative to high-priced liquid-handling robots and bioprinters.
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spelling doaj.art-296ddffeca4c4688b27eb1bb173fa1cb2022-12-21T18:49:56ZengElsevierMaterials & Design0264-12752021-06-01204109619An open-source technology platform to increase reproducibility and enable high-throughput production of tailorable gelatin methacryloyl (GelMA) - based hydrogelsSebastian Eggert0Melanie Kahl1Nathalie Bock2Christoph Meinert3Oliver Friedrich4Dietmar W. Hutmacher5Centre in Regenerative Medicine, Queensland University of Technology, Brisbane 4000, QLD, Australia; School of Mechanical, Medical and Process Engineering, Science and Engineering Faculty, Queensland University of Technology, Brisbane 4000, QLD, Australia; Chair of Medical Materials and Implants, Department of Mechanical Engineering and Munich School of BioEngineering, Technical University of Munich, Garching 85748, Germany; Corresponding authors at: Centre in Regenerative Medicine, Queensland University of Technology, Brisbane 4000, QLD, Australia.Centre in Regenerative Medicine, Queensland University of Technology, Brisbane 4000, QLD, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane 4000, QLD, Australia; Institute of Medical Biotechnology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, GermanyCentre in Regenerative Medicine, Queensland University of Technology, Brisbane 4000, QLD, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane 4000, QLD, Australia; Australian Prostate Cancer Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane 4000, QLD, Australia; Translational Research Institute, Queensland University of Technology, Woolloongabba 4102, QLD, AustraliaCentre in Regenerative Medicine, Queensland University of Technology, Brisbane 4000, QLD, Australia; School of Mechanical, Medical and Process Engineering, Science and Engineering Faculty, Queensland University of Technology, Brisbane 4000, QLD, AustraliaSchool of Mechanical, Medical and Process Engineering, Science and Engineering Faculty, Queensland University of Technology, Brisbane 4000, QLD, Australia; Institute of Medical Biotechnology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, GermanyCentre in Regenerative Medicine, Queensland University of Technology, Brisbane 4000, QLD, Australia; School of Mechanical, Medical and Process Engineering, Science and Engineering Faculty, Queensland University of Technology, Brisbane 4000, QLD, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane 4000, QLD, Australia; Translational Research Institute, Queensland University of Technology, Woolloongabba 4102, QLD, Australia; ARC ITTC in Additive Biomanufacturing, Queensland University of Technology, Brisbane 4000, QLD, Australia; Corresponding authors at: Centre in Regenerative Medicine, Queensland University of Technology, Brisbane 4000, QLD, Australia.Gelatin methacryloyl (GelMA)-based hydrogels have become highly studied as modular tissue culture platforms due to the combination of the bioactivity of gelatin and tailorability of photo-crosslinkable hydrogels. However, current production and characterization workflows still rely on manual, time-consuming, and low-throughput processes, ultimately limiting widespread adaption. To address these challenges, an open-source technology platform is engineered and validated for automated high-throughput production of GelMA-based 3D constructs by integrating automated pipetting capabilities for viscous and non-viscous liquids. Firstly, the platform is applied in combination with inexpensive absorbance measurements to systematically optimize the mixing sequence for GelMA-based precursor solutions. This enables a decrease in the relative standard deviation of the prepared mixtures from 63% to 2.5%, demonstrating a significantly improved reproducibility. Next, the applicability and high-throughput capacity are demonstrated by the reproducible generation of GelMA dilution series with 0.5 and 2% (w/v) concentration steps as well as double network hydrogels consisting of 2% (w/v) alginate and 5% (w/v) GelMA. Finally, a simple and user-friendly methodology is described that integrates Design of Experiments approaches to systematically study the combinatorial effects of material and crosslinking parameters and to establish a parameter library for on-demand production of mechanically defined GelMA-based hydrogels. The platform enables reproducible production and offers an open-source and accessible alternative to high-priced liquid-handling robots and bioprinters.http://www.sciencedirect.com/science/article/pii/S0264127521001726Hydrogels3D cell cultureBioprintingTissue engineeringGelatin methacryloyl (GelMA)Reproducibility
spellingShingle Sebastian Eggert
Melanie Kahl
Nathalie Bock
Christoph Meinert
Oliver Friedrich
Dietmar W. Hutmacher
An open-source technology platform to increase reproducibility and enable high-throughput production of tailorable gelatin methacryloyl (GelMA) - based hydrogels
Materials & Design
Hydrogels
3D cell culture
Bioprinting
Tissue engineering
Gelatin methacryloyl (GelMA)
Reproducibility
title An open-source technology platform to increase reproducibility and enable high-throughput production of tailorable gelatin methacryloyl (GelMA) - based hydrogels
title_full An open-source technology platform to increase reproducibility and enable high-throughput production of tailorable gelatin methacryloyl (GelMA) - based hydrogels
title_fullStr An open-source technology platform to increase reproducibility and enable high-throughput production of tailorable gelatin methacryloyl (GelMA) - based hydrogels
title_full_unstemmed An open-source technology platform to increase reproducibility and enable high-throughput production of tailorable gelatin methacryloyl (GelMA) - based hydrogels
title_short An open-source technology platform to increase reproducibility and enable high-throughput production of tailorable gelatin methacryloyl (GelMA) - based hydrogels
title_sort open source technology platform to increase reproducibility and enable high throughput production of tailorable gelatin methacryloyl gelma based hydrogels
topic Hydrogels
3D cell culture
Bioprinting
Tissue engineering
Gelatin methacryloyl (GelMA)
Reproducibility
url http://www.sciencedirect.com/science/article/pii/S0264127521001726
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