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Fabrication of core-shell spheroids as building blocks for engineering 3D complex vascularized tissue
- Source :
- Acta Biomaterialia. 100:158-172
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Cell spheroids as building blocks for engineering micro-tissue should be able to mimic the complex structure of natural tissue. However, control of the distribution of multiple cell populations within cell spheroids is difficult to achieve with current spheroid-harvest methods such as hanging-drop and with the use of microwell plates. In this study, we report the fabrication of core-shell spheroids with the ultimate goal to form 3D complex micro-tissue. We used endothelial cells and two types of stem cells (human turbinate mesenchymal stem cells (hTMSCs)/adipose-derived stem cells (ADSCs)). The stem cells and endothelial cells formed layered micro-sized cell sheets (µCSs) on polydopamine micro-patterned temperature-responsive hydrogel surfaces by a sequential seeding method, and these layered µCSs self-assembled to form core-shell spheroids by expansion of the hydrogels. The co-cultured spheroids formed a core-shell structure irrespective of stem cell type. In addition, the size of the core-shell spheroids was controlled from 90 ± 1 to 144 ± 3 µm by changing pattern sizes (200, 300, and 400 µm). The shell thickness gradually increased from 12 ± 3 to 30 ± 6 µm by adjusting the endothelial cell seeding density. Finally, we fabricated the micro-tissue by fusion of the co-cultured spheroids, and the spheroids with the core-shell structure rapidly induced in vitro vessel-like network in 3 days. Thus, the position of endothelial cells in co-cultured spheroids may be an important factor for the modulation of the vascularization process, which can be useful for the production of 3D complex micro-tissues using spheroids as building blocks. Statement of significance This manuscript describes our work on the fabrication of core-shell spheroids as building blocks to form 3D complex vascularized micro-tissue. Stem cells (human turbinate mesenchymal stem cells (hTMSCs) or adipose-derived stem cells (ADSCs)) and endothelial cells formed layered micro-sized cell sheets (µCSs) on micro-patterned temperature-responsive hydrogel surfaces by a sequential seeding method, and these layered µCSs self-assembled to form core-shell spheroids (core – stem cells, shell – endothelial cells), irrespective of stem cell type. In addition, the size and shell thickness of the core-shell spheroids were controlled by modifying pattern size and endothelial cell seeding density. We fabricated the vascularized micro-tissue by fusion of the spheroids and demonstrated that the spheroids with a core-shell structure rapidly induced vessel-like network.
- Subjects :
- Materials science
Fabrication
0206 medical engineering
Cell
Biomedical Engineering
Neovascularization, Physiologic
02 engineering and technology
Biochemistry
Fluorescence
Biomaterials
Core shell
Spheroids, Cellular
Human Umbilical Vein Endothelial Cells
medicine
Humans
Molecular Biology
Tissue Engineering
Mesenchymal stem cell
Temperature
Spheroid
Mesenchymal Stem Cells
General Medicine
021001 nanoscience & nanotechnology
020601 biomedical engineering
Endothelial stem cell
medicine.anatomical_structure
embryonic structures
Self-healing hydrogels
Biophysics
Microtechnology
Stem cell
0210 nano-technology
Biotechnology
Subjects
Details
- ISSN :
- 17427061
- Volume :
- 100
- Database :
- OpenAIRE
- Journal :
- Acta Biomaterialia
- Accession number :
- edsair.doi.dedup.....0a69891e3808b0d20661eae5c8f247e7