Stiffness-Controlled Hydrogels for 3D Cell Culture Models
Nanofibrillated cellulose (NFC) hydrogel is a versatile biomaterial suitable, for example, for three-dimensional (3D) cell spheroid culturing, drug delivery, and wound treatment. By freeze-drying NFC hydrogel, highly porous NFC structures can be manufactured. We freeze-dried NFC hydrogel and subsequ...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
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| Series: | Polymers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4360/14/24/5530 |
| _version_ | 1797455565344997376 |
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| author | Arto Merivaara Elle Koivunotko Kalle Manninen Tuomas Kaseva Julia Monola Eero Salli Raili Koivuniemi Sauli Savolainen Sami Valkonen Marjo Yliperttula |
| author_facet | Arto Merivaara Elle Koivunotko Kalle Manninen Tuomas Kaseva Julia Monola Eero Salli Raili Koivuniemi Sauli Savolainen Sami Valkonen Marjo Yliperttula |
| author_sort | Arto Merivaara |
| collection | DOAJ |
| description | Nanofibrillated cellulose (NFC) hydrogel is a versatile biomaterial suitable, for example, for three-dimensional (3D) cell spheroid culturing, drug delivery, and wound treatment. By freeze-drying NFC hydrogel, highly porous NFC structures can be manufactured. We freeze-dried NFC hydrogel and subsequently reconstituted the samples into a variety of concentrations of NFC fibers, which resulted in different stiffness of the material, i.e., different mechanical cues. After the successful freeze-drying and reconstitution, we showed that freeze-dried NFC hydrogel can be used for one-step 3D cell spheroid culturing of primary mesenchymal stem/stromal cells, prostate cancer cells (PC3), and hepatocellular carcinoma cells (HepG2). No difference was observed in the viability or morphology between the 3D cell spheroids cultured in the freeze-dried and reconstituted NFC hydrogel and fresh NFC hydrogel. Furthermore, the 3D cultured spheroids showed stable metabolic activity and nearly 100% viability. Finally, we applied a convolutional neural network (CNN)-based automatic nuclei segmentation approach to automatically segment individual cells of 3D cultured PC3 and HepG2 spheroids. These results provide an application to culture 3D cell spheroids more readily with the NFC hydrogel and a step towards automatization of 3D cell culturing and analysis. |
| first_indexed | 2024-03-09T15:55:08Z |
| format | Article |
| id | doaj.art-118789816a084607861134ccc51321aa |
| institution | Directory Open Access Journal |
| issn | 2073-4360 |
| language | English |
| last_indexed | 2024-03-09T15:55:08Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Polymers |
| spelling | doaj.art-118789816a084607861134ccc51321aa2023-11-24T17:33:42ZengMDPI AGPolymers2073-43602022-12-011424553010.3390/polym14245530Stiffness-Controlled Hydrogels for 3D Cell Culture ModelsArto Merivaara0Elle Koivunotko1Kalle Manninen2Tuomas Kaseva3Julia Monola4Eero Salli5Raili Koivuniemi6Sauli Savolainen7Sami Valkonen8Marjo Yliperttula9Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, FinlandDrug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, FinlandDrug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, FinlandHUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, FinlandDrug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, FinlandHUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, FinlandDrug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, FinlandHUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, FinlandDrug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, FinlandDrug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, FinlandNanofibrillated cellulose (NFC) hydrogel is a versatile biomaterial suitable, for example, for three-dimensional (3D) cell spheroid culturing, drug delivery, and wound treatment. By freeze-drying NFC hydrogel, highly porous NFC structures can be manufactured. We freeze-dried NFC hydrogel and subsequently reconstituted the samples into a variety of concentrations of NFC fibers, which resulted in different stiffness of the material, i.e., different mechanical cues. After the successful freeze-drying and reconstitution, we showed that freeze-dried NFC hydrogel can be used for one-step 3D cell spheroid culturing of primary mesenchymal stem/stromal cells, prostate cancer cells (PC3), and hepatocellular carcinoma cells (HepG2). No difference was observed in the viability or morphology between the 3D cell spheroids cultured in the freeze-dried and reconstituted NFC hydrogel and fresh NFC hydrogel. Furthermore, the 3D cultured spheroids showed stable metabolic activity and nearly 100% viability. Finally, we applied a convolutional neural network (CNN)-based automatic nuclei segmentation approach to automatically segment individual cells of 3D cultured PC3 and HepG2 spheroids. These results provide an application to culture 3D cell spheroids more readily with the NFC hydrogel and a step towards automatization of 3D cell culturing and analysis.https://www.mdpi.com/2073-4360/14/24/5530freeze-dryingnanofibrillated cellulose3D cell culturehydrogelbiomaterialsconvolutional neural network |
| spellingShingle | Arto Merivaara Elle Koivunotko Kalle Manninen Tuomas Kaseva Julia Monola Eero Salli Raili Koivuniemi Sauli Savolainen Sami Valkonen Marjo Yliperttula Stiffness-Controlled Hydrogels for 3D Cell Culture Models Polymers freeze-drying nanofibrillated cellulose 3D cell culture hydrogel biomaterials convolutional neural network |
| title | Stiffness-Controlled Hydrogels for 3D Cell Culture Models |
| title_full | Stiffness-Controlled Hydrogels for 3D Cell Culture Models |
| title_fullStr | Stiffness-Controlled Hydrogels for 3D Cell Culture Models |
| title_full_unstemmed | Stiffness-Controlled Hydrogels for 3D Cell Culture Models |
| title_short | Stiffness-Controlled Hydrogels for 3D Cell Culture Models |
| title_sort | stiffness controlled hydrogels for 3d cell culture models |
| topic | freeze-drying nanofibrillated cellulose 3D cell culture hydrogel biomaterials convolutional neural network |
| url | https://www.mdpi.com/2073-4360/14/24/5530 |
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