Abstract
Scaffold-based bone tissue engineering strategies fail to meet the clinical need to fabricate patient-specific and defect shape-specific, anatomically relevant load-bearing bone constructs. 3D bioprinting strategies are gaining major interest as a potential alternative, but design of a specific bioink is still a major challenge that can modulate key signaling pathways to induce osteogenic differentiation of progenitor cells, as well as offer appropriate microenvironment to augment mineralization. In the present study, we developed silk fibroin protein and gelatin-based conjugated bioink, which showed localized presence and sustained release of calcium. Presence of 2.6 mM Ca 2+ ions within the bioink could further induce enhanced osteogenesis of Bone marrow derived progenitor cells (hMSCs) compared to the bioink without calcium, or same concentration of calcium added to the media, as evidenced by upregulated gene expression of osteogenic markers. This study generated unprecedented mechanistic insights on the role of fibroin-gelatin-CaCl 2 bioink in modulating expression of several proteins which are known to play crucial role in bone regeneration as well as key signaling pathways such as β-catenin, BMP signaling pathway, Parathyroid hormone-dependent signaling pathway, Forkhead box O (FOXO) pathway, and Hippo pathways in hMSC-laden bioprinted constructs.
| Original language | English |
|---|---|
| Pages (from-to) | 1518-1533 |
| Number of pages | 16 |
| Journal | ACS Biomaterials Science and Engineering |
| Volume | 5 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Feb 12 2019 |
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Keywords
- 3D bioprinting
- extracellular calcium
- osteogenesis
- signaling pathways
- silk bioink
ASJC Scopus subject areas
- Biomaterials
- Biomedical Engineering
Cite this
Investigating the Role of Sustained Calcium Release in Silk-Gelatin-Based Three-Dimensional Bioprinted Constructs for Enhancing the Osteogenic Differentiation of Human Bone Marrow Derived Mesenchymal Stromal Cells. / Sharma, Aarushi; Desando, Giovanna; Petretta, Mauro; Chawla, Shikha; Bartolotti, Isabella; Manferdini, Cristina; Paolella, Francesca; Gabusi, Elena; Trucco, Diego; Ghosh, Sourabh; Lisignoli, Gina.
In: ACS Biomaterials Science and Engineering, Vol. 5, No. 3, 12.02.2019, p. 1518-1533.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Investigating the Role of Sustained Calcium Release in Silk-Gelatin-Based Three-Dimensional Bioprinted Constructs for Enhancing the Osteogenic Differentiation of Human Bone Marrow Derived Mesenchymal Stromal Cells
AU - Sharma, Aarushi
AU - Desando, Giovanna
AU - Petretta, Mauro
AU - Chawla, Shikha
AU - Bartolotti, Isabella
AU - Manferdini, Cristina
AU - Paolella, Francesca
AU - Gabusi, Elena
AU - Trucco, Diego
AU - Ghosh, Sourabh
AU - Lisignoli, Gina
PY - 2019/2/12
Y1 - 2019/2/12
N2 - Scaffold-based bone tissue engineering strategies fail to meet the clinical need to fabricate patient-specific and defect shape-specific, anatomically relevant load-bearing bone constructs. 3D bioprinting strategies are gaining major interest as a potential alternative, but design of a specific bioink is still a major challenge that can modulate key signaling pathways to induce osteogenic differentiation of progenitor cells, as well as offer appropriate microenvironment to augment mineralization. In the present study, we developed silk fibroin protein and gelatin-based conjugated bioink, which showed localized presence and sustained release of calcium. Presence of 2.6 mM Ca 2+ ions within the bioink could further induce enhanced osteogenesis of Bone marrow derived progenitor cells (hMSCs) compared to the bioink without calcium, or same concentration of calcium added to the media, as evidenced by upregulated gene expression of osteogenic markers. This study generated unprecedented mechanistic insights on the role of fibroin-gelatin-CaCl 2 bioink in modulating expression of several proteins which are known to play crucial role in bone regeneration as well as key signaling pathways such as β-catenin, BMP signaling pathway, Parathyroid hormone-dependent signaling pathway, Forkhead box O (FOXO) pathway, and Hippo pathways in hMSC-laden bioprinted constructs.
AB - Scaffold-based bone tissue engineering strategies fail to meet the clinical need to fabricate patient-specific and defect shape-specific, anatomically relevant load-bearing bone constructs. 3D bioprinting strategies are gaining major interest as a potential alternative, but design of a specific bioink is still a major challenge that can modulate key signaling pathways to induce osteogenic differentiation of progenitor cells, as well as offer appropriate microenvironment to augment mineralization. In the present study, we developed silk fibroin protein and gelatin-based conjugated bioink, which showed localized presence and sustained release of calcium. Presence of 2.6 mM Ca 2+ ions within the bioink could further induce enhanced osteogenesis of Bone marrow derived progenitor cells (hMSCs) compared to the bioink without calcium, or same concentration of calcium added to the media, as evidenced by upregulated gene expression of osteogenic markers. This study generated unprecedented mechanistic insights on the role of fibroin-gelatin-CaCl 2 bioink in modulating expression of several proteins which are known to play crucial role in bone regeneration as well as key signaling pathways such as β-catenin, BMP signaling pathway, Parathyroid hormone-dependent signaling pathway, Forkhead box O (FOXO) pathway, and Hippo pathways in hMSC-laden bioprinted constructs.
KW - 3D bioprinting
KW - extracellular calcium
KW - osteogenesis
KW - signaling pathways
KW - silk bioink
UR - http://www.scopus.com/inward/record.url?scp=85062798130&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062798130&partnerID=8YFLogxK
U2 - 10.1021/acsbiomaterials.8b01631
DO - 10.1021/acsbiomaterials.8b01631
M3 - Article
AN - SCOPUS:85062798130
VL - 5
SP - 1518
EP - 1533
JO - ACS Biomaterials Science and Engineering
JF - ACS Biomaterials Science and Engineering
SN - 2373-9878
IS - 3
ER -