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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
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 days 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 days 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
1758-5082
Cidonio, Gianluca
558ad583-899a-4d8c-b42b-bc1c354c8757
Glinka, Michael
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Kim, Yanghee
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Kanczler, Janos
eb8db9ff-a038-475f-9030-48eef2b0559c
Lanham, Stuart
28fdbbef-e3b6-4fdf-bd0f-4968eeb614d6
Ahlfeld, T.
e7376b44-1dff-482e-ae3f-cabda3b294d7
Lode, Anja
03670eff-fd29-4a5e-b3da-4f48797b81ec
Dawson, Jonathan
b220fe76-498d-47be-9995-92da6c289cf3
Gelinsky, M.
72546c96-7c96-430a-9862-75953a2678ea
Oreffo, Richard
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Cidonio, Gianluca
558ad583-899a-4d8c-b42b-bc1c354c8757
Glinka, Michael
7630ab6c-91c5-4840-9c25-12cb61fcb91e
Kim, Yanghee
de0d641b-c2cb-4e73-9ae2-e20d33689f5d
Kanczler, Janos
eb8db9ff-a038-475f-9030-48eef2b0559c
Lanham, Stuart
28fdbbef-e3b6-4fdf-bd0f-4968eeb614d6
Ahlfeld, T.
e7376b44-1dff-482e-ae3f-cabda3b294d7
Lode, Anja
03670eff-fd29-4a5e-b3da-4f48797b81ec
Dawson, Jonathan
b220fe76-498d-47be-9995-92da6c289cf3
Gelinsky, M.
72546c96-7c96-430a-9862-75953a2678ea
Oreffo, Richard
ff9fff72-6855-4d0f-bfb2-311d0e8f3778

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. (doi:10.1088/1758-5090/ab8753/meta).

Record type: Article

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 days 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 days 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

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Nanoclay based 3D printed scaffolds accepted manuscript - Accepted Manuscript
Available under License Creative Commons Attribution.
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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
ORCID for Janos Kanczler: ORCID iD orcid.org/0000-0001-7249-0414
ORCID for Stuart Lanham: ORCID iD orcid.org/0000-0002-4516-264X
ORCID for Jonathan Dawson: ORCID iD orcid.org/0000-0002-6712-0598
ORCID for Richard Oreffo: ORCID iD orcid.org/0000-0001-5995-6726

Catalogue record

Date deposited: 16 Apr 2020 16:30
Last modified: 18 Feb 2021 17:11

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Contributors

Author: Michael Glinka
Author: Yanghee Kim
Author: Janos Kanczler ORCID iD
Author: Stuart Lanham ORCID iD
Author: T. Ahlfeld
Author: Anja Lode
Author: Jonathan Dawson ORCID iD
Author: M. Gelinsky
Author: Richard Oreffo ORCID iD

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