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Hybrid bioprinting of chondrogenically induced human mesenchymal stem cell spheroids

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Abstract
To date, the treatment of articular cartilage lesions remains challenging. A promising strategy for the development of new regenerative therapies is hybrid bioprinting, combining the principles of developmental biology, biomaterial science, and 3D bioprinting. In this approach, scaffold-free cartilage microtissues with small diameters are used as building blocks, combined with a photo-crosslinkable hydrogel and subsequently bioprinted. Spheroids of human bone marrow-derived mesenchymal stem cells (hBM-MSC) are created using a high-throughput microwell system and chondrogenic differentiation is induced during 42 days by applying chondrogenic culture medium and low oxygen tension (5%). Stable and homogeneous cartilage spheroids with a mean diameter of 116 +/- 2.80 mu m, which is compatible with bioprinting, were created after 14 days of culture and a glycosaminoglycans (GAG)- and collagen II-positive extracellular matrix (ECM) was observed. Spheroids were able to assemble at random into a macrotissue, driven by developmental biology tissue fusion processes, and after 72 h of culture, a compact macrotissue was formed. In a directed assembly approach, spheroids were assembled with high spatial control using the bio-ink based extrusion bioprinting approach. Therefore, 14-day spheroids were combined with a photo-crosslinkable methacrylamide-modified gelatin (gelMA) as viscous printing medium to ensure shape fidelity of the printed construct. The photo-initiators Irgacure 2959 and Li-TPO-L were evaluated by assessing their effect on bio-ink properties and the chondrogenic phenotype. The encapsulation in gelMA resulted in further chondrogenic maturation observed by an increased production of GAG and a reduction of collagen I. Moreover, the use of Li-TPO-L lead to constructs with lower stiffness which induced a decrease of collagen I and an increase in GAG and collagen II production. After 3D bioprinting, spheroids remained viable and the cartilage phenotype was maintained. Our findings demonstrate that hBM-MSC spheroids are able to differentiate into cartilage microtissues and display a geometry compatible with 3D bioprinting. Furthermore, for hybrid bioprinting of these spheroids, gelMA is a promising material as it exhibits favorable properties in terms of printability and it supports the viability and chondrogenic phenotype of hBM-MSC microtissues. Moreover, it was shown that a lower hydrogel stiffness enhances further chondrogenic maturation after bioprinting.
Keywords
Biotechnology, Bioengineering, Histology, Biomedical Engineering, bioprinting, spheroids, chondrogenesis, differentiation, stem cell, fusion, self-assembly, AUTOLOGOUS CHONDROCYTE IMPLANTATION, CARTILAGE, HYDROGELS, REDIFFERENTIATION, DIFFERENTIATION, KNEE, POLYMERIZATION, SCAFFOLDS, DENSITY, 2D

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MLA
De Moor, Lise, et al. “Hybrid Bioprinting of Chondrogenically Induced Human Mesenchymal Stem Cell Spheroids.” FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, vol. 8, 2020, doi:10.3389/fbioe.2020.00484.
APA
De Moor, L., Fernandez, S., Vercruysse, C., Tytgat, L., Asadian, M., De Geyter, N., … Declercq, H. (2020). Hybrid bioprinting of chondrogenically induced human mesenchymal stem cell spheroids. FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, 8. https://doi.org/10.3389/fbioe.2020.00484
Chicago author-date
De Moor, Lise, Sélina Fernandez, Chris Vercruysse, Liesbeth Tytgat, Mahtab Asadian, Nathalie De Geyter, Sandra Van Vlierberghe, Peter Dubruel, and Heidi Declercq. 2020. “Hybrid Bioprinting of Chondrogenically Induced Human Mesenchymal Stem Cell Spheroids.” FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY 8. https://doi.org/10.3389/fbioe.2020.00484.
Chicago author-date (all authors)
De Moor, Lise, Sélina Fernandez, Chris Vercruysse, Liesbeth Tytgat, Mahtab Asadian, Nathalie De Geyter, Sandra Van Vlierberghe, Peter Dubruel, and Heidi Declercq. 2020. “Hybrid Bioprinting of Chondrogenically Induced Human Mesenchymal Stem Cell Spheroids.” FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY 8. doi:10.3389/fbioe.2020.00484.
Vancouver
1.
De Moor L, Fernandez S, Vercruysse C, Tytgat L, Asadian M, De Geyter N, et al. Hybrid bioprinting of chondrogenically induced human mesenchymal stem cell spheroids. FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY. 2020;8.
IEEE
[1]
L. De Moor et al., “Hybrid bioprinting of chondrogenically induced human mesenchymal stem cell spheroids,” FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, vol. 8, 2020.
@article{8663083,
  abstract     = {{To date, the treatment of articular cartilage lesions remains challenging. A promising strategy for the development of new regenerative therapies is hybrid bioprinting, combining the principles of developmental biology, biomaterial science, and 3D bioprinting. In this approach, scaffold-free cartilage microtissues with small diameters are used as building blocks, combined with a photo-crosslinkable hydrogel and subsequently bioprinted. Spheroids of human bone marrow-derived mesenchymal stem cells (hBM-MSC) are created using a high-throughput microwell system and chondrogenic differentiation is induced during 42 days by applying chondrogenic culture medium and low oxygen tension (5%). Stable and homogeneous cartilage spheroids with a mean diameter of 116 +/- 2.80 mu m, which is compatible with bioprinting, were created after 14 days of culture and a glycosaminoglycans (GAG)- and collagen II-positive extracellular matrix (ECM) was observed. Spheroids were able to assemble at random into a macrotissue, driven by developmental biology tissue fusion processes, and after 72 h of culture, a compact macrotissue was formed. In a directed assembly approach, spheroids were assembled with high spatial control using the bio-ink based extrusion bioprinting approach. Therefore, 14-day spheroids were combined with a photo-crosslinkable methacrylamide-modified gelatin (gelMA) as viscous printing medium to ensure shape fidelity of the printed construct. The photo-initiators Irgacure 2959 and Li-TPO-L were evaluated by assessing their effect on bio-ink properties and the chondrogenic phenotype. The encapsulation in gelMA resulted in further chondrogenic maturation observed by an increased production of GAG and a reduction of collagen I. Moreover, the use of Li-TPO-L lead to constructs with lower stiffness which induced a decrease of collagen I and an increase in GAG and collagen II production. After 3D bioprinting, spheroids remained viable and the cartilage phenotype was maintained. Our findings demonstrate that hBM-MSC spheroids are able to differentiate into cartilage microtissues and display a geometry compatible with 3D bioprinting. Furthermore, for hybrid bioprinting of these spheroids, gelMA is a promising material as it exhibits favorable properties in terms of printability and it supports the viability and chondrogenic phenotype of hBM-MSC microtissues. Moreover, it was shown that a lower hydrogel stiffness enhances further chondrogenic maturation after bioprinting.}},
  articleno    = {{484}},
  author       = {{De Moor, Lise and Fernandez, Sélina and Vercruysse, Chris and Tytgat, Liesbeth and Asadian, Mahtab and De Geyter, Nathalie and Van Vlierberghe, Sandra and Dubruel, Peter and Declercq, Heidi}},
  issn         = {{2296-4185}},
  journal      = {{FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY}},
  keywords     = {{Biotechnology,Bioengineering,Histology,Biomedical Engineering,bioprinting,spheroids,chondrogenesis,differentiation,stem cell,fusion,self-assembly,AUTOLOGOUS CHONDROCYTE IMPLANTATION,CARTILAGE,HYDROGELS,REDIFFERENTIATION,DIFFERENTIATION,KNEE,POLYMERIZATION,SCAFFOLDS,DENSITY,2D}},
  language     = {{eng}},
  pages        = {{20}},
  title        = {{Hybrid bioprinting of chondrogenically induced human mesenchymal stem cell spheroids}},
  url          = {{http://dx.doi.org/10.3389/fbioe.2020.00484}},
  volume       = {{8}},
  year         = {{2020}},
}

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