Nanoclay-based 3D printed scaffolds promote vascular ingrowth ex vivo and generate bone mineral tissue in vitro and in vivo
Nanoclay-based 3D printed scaffolds promote vascular ingrowth ex vivo and generate bone mineral tissue in vitro and in vivo
Acellular soft hydrogels are not ideal for hard tissue engineering given their poor mechanical stability, however, in combination with cellular components offer significant promise for tissue regeneration. Indeed, nanocomposite bioinks provide an attractive platform to deliver human bone marrow stromal cells (HBMSCs) in three dimensions producing cell-laden constructs that aim to facilitate bone repair and functionality. Here we present the in vitro, ex vivo and in vivo investigation of bioprinted HBMSCs encapsulated in a nanoclay-based bioink to produce viable and functional three-dimensional constructs. HBMSC-laden constructs remained viable over 21 d in vitro and immediately functional when conditioned with osteogenic media. 3D scaffolds seeded with human umbilical vein endothelial cells (HUVECs) and loaded with vascular endothelial growth factor (VEGF) implanted ex vivo into a chick chorioallantoic membrane (CAM) model showed integration and vascularisation after 7 d of incubation. In a pre-clinical in vivo application of a nanoclay-based bioink to regenerate skeletal tissue, we demonstrated bone morphogenetic protein-2 (BMP-2) absorbed scaffolds produced extensive mineralisation after 4 weeks (p < 0.0001) compared to the drug-free and alginate controls. In addition, HBMSC-laden 3D printed scaffolds were found to significantly (p < 0.0001) support bone tissue formation in vivo compared to acellular and cast scaffolds. These studies illustrate the potential of nanoclay-based bioink, to produce viable and functional constructs for clinically relevant skeletal tissue regeneration.
Cidonio, Gianluca
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Glinka, Michael
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Kim, Yanghee
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Kanczler, Janos
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Lanham, Stuart
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Ahlfeld, T.
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Lode, Anja
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Dawson, Jonathan
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Gelinsky, M.
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Oreffo, Richard
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Cidonio, Gianluca
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Glinka, Michael
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Kim, Yanghee
de0d641b-c2cb-4e73-9ae2-e20d33689f5d
Kanczler, Janos
eb8db9ff-a038-475f-9030-48eef2b0559c
Lanham, Stuart
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Ahlfeld, T.
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Lode, Anja
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Dawson, Jonathan
b220fe76-498d-47be-9995-92da6c289cf3
Gelinsky, M.
72546c96-7c96-430a-9862-75953a2678ea
Oreffo, Richard
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Cidonio, Gianluca, Glinka, Michael, Kim, Yanghee, Kanczler, Janos, Lanham, Stuart, Ahlfeld, T., Lode, Anja, Dawson, Jonathan, Gelinsky, M. and Oreffo, Richard
(2020)
Nanoclay-based 3D printed scaffolds promote vascular ingrowth ex vivo and generate bone mineral tissue in vitro and in vivo.
Biofabrication, 12 (3).
(doi:10.1088/1758-5090/ab8753/meta).
Abstract
Acellular soft hydrogels are not ideal for hard tissue engineering given their poor mechanical stability, however, in combination with cellular components offer significant promise for tissue regeneration. Indeed, nanocomposite bioinks provide an attractive platform to deliver human bone marrow stromal cells (HBMSCs) in three dimensions producing cell-laden constructs that aim to facilitate bone repair and functionality. Here we present the in vitro, ex vivo and in vivo investigation of bioprinted HBMSCs encapsulated in a nanoclay-based bioink to produce viable and functional three-dimensional constructs. HBMSC-laden constructs remained viable over 21 d in vitro and immediately functional when conditioned with osteogenic media. 3D scaffolds seeded with human umbilical vein endothelial cells (HUVECs) and loaded with vascular endothelial growth factor (VEGF) implanted ex vivo into a chick chorioallantoic membrane (CAM) model showed integration and vascularisation after 7 d of incubation. In a pre-clinical in vivo application of a nanoclay-based bioink to regenerate skeletal tissue, we demonstrated bone morphogenetic protein-2 (BMP-2) absorbed scaffolds produced extensive mineralisation after 4 weeks (p < 0.0001) compared to the drug-free and alginate controls. In addition, HBMSC-laden 3D printed scaffolds were found to significantly (p < 0.0001) support bone tissue formation in vivo compared to acellular and cast scaffolds. These studies illustrate the potential of nanoclay-based bioink, to produce viable and functional constructs for clinically relevant skeletal tissue regeneration.
Text
Nanoclay based 3D printed scaffolds accepted manuscript
- Accepted Manuscript
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Accepted/In Press date: 7 April 2020
e-pub ahead of print date: 7 April 2020
Identifiers
Local EPrints ID: 439327
URI: http://eprints.soton.ac.uk/id/eprint/439327
ISSN: 1758-5082
PURE UUID: 9f3ebb5d-0347-49db-b9c6-4e602d62867c
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Date deposited: 16 Apr 2020 16:30
Last modified: 17 Mar 2024 03:41
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Contributors
Author:
Gianluca Cidonio
Author:
Michael Glinka
Author:
Janos Kanczler
Author:
Stuart Lanham
Author:
T. Ahlfeld
Author:
Anja Lode
Author:
M. Gelinsky
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