Details
Original language | English |
---|---|
Journal | Advanced healthcare materials |
Early online date | 8 Jun 2025 |
Publication status | E-pub ahead of print - 8 Jun 2025 |
Abstract
Mesenchymal stem cells (MSCs) hold potential for several applications, but inefficient nonphysiological culturing methods constantly prevent clinical translation. Automated cell encapsulation in small hydrogels (microgels) facilitates physiologically relevant MSC expansion in bioreactors. Unfortunately, encapsulation processes are poorly characterized, biological variability is seldomly considered, and dynamic culturing is marginally explored. Here, a high-throughput millifluidic encapsulation process is introduced and standardized. This platform enables highly viable MSC networks within gelatin methacryloyl microgels. The impact of biological variability and crosslinking variations under strong dynamic culturing conditions is closely monitored through cell proliferation, microgel shrinkage, and metabolic activity. The effect of carboxymethyl cellulose on microgel's architecture is observed with cryogenic scanning electron microscopy. Increased crosslinking controls the formation of an outer layer on the microgels, which improves the microgel's resistance to shrinking, prevents cell proliferation on the material's surface and increases overall MSC expansion. Cell proliferation, microgel shrinkage, glucose uptake, and cell metabolism show interdependencies observable thanks to the high encapsulation output. Cell proliferation and metabolic activity depend strongly on donor-to-donor variability and change during culture. However, metabolic readouts reliably follow cell expansion, which makes this simple and mechanically robust platform promising for large-scale bioreactor applications.
Keywords
- 3D culture, Cryo-SEM, encapsulation, fluidics, hydrogels, mesenchymal stem cells
ASJC Scopus subject areas
- Materials Science(all)
- Biomaterials
- Engineering(all)
- Biomedical Engineering
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmaceutical Science
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In: Advanced healthcare materials, 08.06.2025.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - High-Throughput Encapsulation of Stem Cells
T2 - Characterizing Dynamic Culture Variability With a Millifluidic Approach
AU - García-Aponte, Oscar Fabian
AU - Serra, Marta
AU - Kahlenberg, Simon
AU - Subbiahdoss, Guruprakash
AU - Reimhult, Erik
AU - Egger, Dominik
AU - Kasper, Cornelia
N1 - Publisher Copyright: © 2025 The Author(s). Advanced Healthcare Materials published by Wiley-VCH GmbH.
PY - 2025/6/8
Y1 - 2025/6/8
N2 - Mesenchymal stem cells (MSCs) hold potential for several applications, but inefficient nonphysiological culturing methods constantly prevent clinical translation. Automated cell encapsulation in small hydrogels (microgels) facilitates physiologically relevant MSC expansion in bioreactors. Unfortunately, encapsulation processes are poorly characterized, biological variability is seldomly considered, and dynamic culturing is marginally explored. Here, a high-throughput millifluidic encapsulation process is introduced and standardized. This platform enables highly viable MSC networks within gelatin methacryloyl microgels. The impact of biological variability and crosslinking variations under strong dynamic culturing conditions is closely monitored through cell proliferation, microgel shrinkage, and metabolic activity. The effect of carboxymethyl cellulose on microgel's architecture is observed with cryogenic scanning electron microscopy. Increased crosslinking controls the formation of an outer layer on the microgels, which improves the microgel's resistance to shrinking, prevents cell proliferation on the material's surface and increases overall MSC expansion. Cell proliferation, microgel shrinkage, glucose uptake, and cell metabolism show interdependencies observable thanks to the high encapsulation output. Cell proliferation and metabolic activity depend strongly on donor-to-donor variability and change during culture. However, metabolic readouts reliably follow cell expansion, which makes this simple and mechanically robust platform promising for large-scale bioreactor applications.
AB - Mesenchymal stem cells (MSCs) hold potential for several applications, but inefficient nonphysiological culturing methods constantly prevent clinical translation. Automated cell encapsulation in small hydrogels (microgels) facilitates physiologically relevant MSC expansion in bioreactors. Unfortunately, encapsulation processes are poorly characterized, biological variability is seldomly considered, and dynamic culturing is marginally explored. Here, a high-throughput millifluidic encapsulation process is introduced and standardized. This platform enables highly viable MSC networks within gelatin methacryloyl microgels. The impact of biological variability and crosslinking variations under strong dynamic culturing conditions is closely monitored through cell proliferation, microgel shrinkage, and metabolic activity. The effect of carboxymethyl cellulose on microgel's architecture is observed with cryogenic scanning electron microscopy. Increased crosslinking controls the formation of an outer layer on the microgels, which improves the microgel's resistance to shrinking, prevents cell proliferation on the material's surface and increases overall MSC expansion. Cell proliferation, microgel shrinkage, glucose uptake, and cell metabolism show interdependencies observable thanks to the high encapsulation output. Cell proliferation and metabolic activity depend strongly on donor-to-donor variability and change during culture. However, metabolic readouts reliably follow cell expansion, which makes this simple and mechanically robust platform promising for large-scale bioreactor applications.
KW - 3D culture
KW - Cryo-SEM
KW - encapsulation
KW - fluidics
KW - hydrogels
KW - mesenchymal stem cells
UR - http://www.scopus.com/inward/record.url?scp=105007829723&partnerID=8YFLogxK
U2 - 10.1002/adhm.202405137
DO - 10.1002/adhm.202405137
M3 - Article
AN - SCOPUS:105007829723
JO - Advanced healthcare materials
JF - Advanced healthcare materials
SN - 2192-2640
ER -