Ultrasound-generated bubbles enhance osteogenic differentiation of mesenchymal stromal cells in composite collagen hydrogels
Hydrogels can improve the delivery of mesenchymal stromal cells (MSCs) by providing crucial biophysical cues that mimic the extracellular matrix. The differentiation of MSCs is dependent on biophysical cues like stiffness and viscoelasticity, yet conventional hydrogels cannot be dynamically altered...
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KeAi Communications Co., Ltd.
2025-01-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X24004134 |
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| author | Somnath Maji Mitra Aliabouzar Carole Quesada Anjali Chiravuri Aidan Macpherson Abigail Pinch Karsyn Kazyak Ziyad Emara Bachir A. Abeid Robert N. Kent, III Firaol S. Midekssa Man Zhang Brendon M. Baker Renny T. Franceschi Mario L. Fabiilli |
| author_facet | Somnath Maji Mitra Aliabouzar Carole Quesada Anjali Chiravuri Aidan Macpherson Abigail Pinch Karsyn Kazyak Ziyad Emara Bachir A. Abeid Robert N. Kent, III Firaol S. Midekssa Man Zhang Brendon M. Baker Renny T. Franceschi Mario L. Fabiilli |
| author_sort | Somnath Maji |
| collection | DOAJ |
| description | Hydrogels can improve the delivery of mesenchymal stromal cells (MSCs) by providing crucial biophysical cues that mimic the extracellular matrix. The differentiation of MSCs is dependent on biophysical cues like stiffness and viscoelasticity, yet conventional hydrogels cannot be dynamically altered after fabrication and implantation to actively direct differentiation. We developed a composite hydrogel, consisting of type I collagen and phase-shift emulsion, where osteogenic differentiation of MSCs can be non-invasively modulated using ultrasound. When exposed to ultrasound, the emulsion within the hydrogel was non-thermally vaporized into bubbles, which locally compacted and stiffened the collagen matrix surrounding each bubble. Bubble growth and matrix compaction were correlated, with collagen regions proximal (i.e., ≤ ∼60 μm) to the bubble displaying a 2.5-fold increase in Young's modulus compared to distal regions (i.e., > ∼60 μm). The viability and proliferation of MSCs, which were encapsulated within the composite hydrogel, were not impacted by bubble formation. In vitro and in vivo studies revealed encapsulated MSCs exhibited significantly elevated levels of RUNX2 and osteocalcin, markers of osteogenic differentiation, in collagen regions proximal to the bubble compared to distal regions. Additionally, alkaline phosphatase activity and calcium deposition were enhanced adjacent to the bubble. An opposite trend was observed for CD90, a marker of MSC stemness. Following subcutaneous implantation, bubbles persisted in the hydrogels for two weeks, which led to localized collagen alignment and increases in nuclear asymmetry. These results are a significant step toward controlling the 3D differentiation of MSCs in a non-invasive and on-demand manner. |
| format | Article |
| id | doaj-art-81b099d5ebfa4d7aa354f8695d4cdc63 |
| institution | OA Journals |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-81b099d5ebfa4d7aa354f8695d4cdc632025-08-20T02:33:06ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-01-0143829710.1016/j.bioactmat.2024.09.018Ultrasound-generated bubbles enhance osteogenic differentiation of mesenchymal stromal cells in composite collagen hydrogelsSomnath Maji0Mitra Aliabouzar1Carole Quesada2Anjali Chiravuri3Aidan Macpherson4Abigail Pinch5Karsyn Kazyak6Ziyad Emara7Bachir A. Abeid8Robert N. Kent, III9Firaol S. Midekssa10Man Zhang11Brendon M. Baker12Renny T. Franceschi13Mario L. Fabiilli14Department of Radiology, University of Michigan, Ann Arbor, MI, USADepartment of Radiology, University of Michigan, Ann Arbor, MI, USA; Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USADepartment of Radiology, University of Michigan, Ann Arbor, MI, USADepartment of Radiology, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USADepartment of Radiology, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USADepartment of Radiology, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USADepartment of Radiology, University of Michigan, Ann Arbor, MI, USADepartment of Radiology, University of Michigan, Ann Arbor, MI, USADepartment of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USADepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USADepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USADepartment of Radiology, University of Michigan, Ann Arbor, MI, USADepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USADepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, MI, USADepartment of Radiology, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Applied Physics Program, University of Michigan, Ann Arbor, MI, USA; Corresponding author. University of Michigan, 1301 Catherine Street, 6436C Medical Sciences Building I, Ann Arbor, MI, 48109, USA.Hydrogels can improve the delivery of mesenchymal stromal cells (MSCs) by providing crucial biophysical cues that mimic the extracellular matrix. The differentiation of MSCs is dependent on biophysical cues like stiffness and viscoelasticity, yet conventional hydrogels cannot be dynamically altered after fabrication and implantation to actively direct differentiation. We developed a composite hydrogel, consisting of type I collagen and phase-shift emulsion, where osteogenic differentiation of MSCs can be non-invasively modulated using ultrasound. When exposed to ultrasound, the emulsion within the hydrogel was non-thermally vaporized into bubbles, which locally compacted and stiffened the collagen matrix surrounding each bubble. Bubble growth and matrix compaction were correlated, with collagen regions proximal (i.e., ≤ ∼60 μm) to the bubble displaying a 2.5-fold increase in Young's modulus compared to distal regions (i.e., > ∼60 μm). The viability and proliferation of MSCs, which were encapsulated within the composite hydrogel, were not impacted by bubble formation. In vitro and in vivo studies revealed encapsulated MSCs exhibited significantly elevated levels of RUNX2 and osteocalcin, markers of osteogenic differentiation, in collagen regions proximal to the bubble compared to distal regions. Additionally, alkaline phosphatase activity and calcium deposition were enhanced adjacent to the bubble. An opposite trend was observed for CD90, a marker of MSC stemness. Following subcutaneous implantation, bubbles persisted in the hydrogels for two weeks, which led to localized collagen alignment and increases in nuclear asymmetry. These results are a significant step toward controlling the 3D differentiation of MSCs in a non-invasive and on-demand manner.http://www.sciencedirect.com/science/article/pii/S2452199X24004134UltrasoundAcoustic droplet vaporizationCollagenMesenchymal stromal cellDifferentiationMechanobiology |
| spellingShingle | Somnath Maji Mitra Aliabouzar Carole Quesada Anjali Chiravuri Aidan Macpherson Abigail Pinch Karsyn Kazyak Ziyad Emara Bachir A. Abeid Robert N. Kent, III Firaol S. Midekssa Man Zhang Brendon M. Baker Renny T. Franceschi Mario L. Fabiilli Ultrasound-generated bubbles enhance osteogenic differentiation of mesenchymal stromal cells in composite collagen hydrogels Bioactive Materials Ultrasound Acoustic droplet vaporization Collagen Mesenchymal stromal cell Differentiation Mechanobiology |
| title | Ultrasound-generated bubbles enhance osteogenic differentiation of mesenchymal stromal cells in composite collagen hydrogels |
| title_full | Ultrasound-generated bubbles enhance osteogenic differentiation of mesenchymal stromal cells in composite collagen hydrogels |
| title_fullStr | Ultrasound-generated bubbles enhance osteogenic differentiation of mesenchymal stromal cells in composite collagen hydrogels |
| title_full_unstemmed | Ultrasound-generated bubbles enhance osteogenic differentiation of mesenchymal stromal cells in composite collagen hydrogels |
| title_short | Ultrasound-generated bubbles enhance osteogenic differentiation of mesenchymal stromal cells in composite collagen hydrogels |
| title_sort | ultrasound generated bubbles enhance osteogenic differentiation of mesenchymal stromal cells in composite collagen hydrogels |
| topic | Ultrasound Acoustic droplet vaporization Collagen Mesenchymal stromal cell Differentiation Mechanobiology |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X24004134 |
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