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Osteogenic and angiogenic tissue formation in high fidelity nanocomposite Laponite-gelatin bioinks

Osteogenic and angiogenic tissue formation in high fidelity nanocomposite Laponite-gelatin bioinks
Osteogenic and angiogenic tissue formation in high fidelity nanocomposite Laponite-gelatin bioinks
Bioprinting of living cells is rapidly developing as an advanced biofabrication approach to engineer tissues. Bioinks can be extruded in three-dimensions (3D) to fabricate complex and hierarchical constructs for implantation. However, lack of functionality can often be attributed to poor bioink properties. Indeed, advanced bioinks encapsulating living cells should: (i) present optimal rheological properties and retain 3D structure post-fabrication, (ii) promote cell viability and support cell differentiation, (iii) localise proteins of interest (e.g. vascular endothelial growth factor (VEGF)) to stimulate encapsulated cell activity and tissue ingrowth upon implantation. In this study, we present the results of the inclusion of a synthetic nanoclay, Laponite (LPN) together with a gelatin methacryloyl (GelMA) bioink and the development of a functional cell-instructive bioink. A nanocomposite bioink displaying enhanced shape fidelity retention and interconnected porosity within extrusion-bioprinted fibres was observed. Human bone marrow stromal cell (HBMSC) viability within the nanocomposite showed no significant changes over 21 days of culture in LPN-GelMA (85.60 ± 10.27 %), compared to a significant decrease in GelMA from 7 (95.88 ± 2.90 %) to 21 days (55.54 ± 14.72 %) (p<0.01). HBMSCs were observed to proliferate in LPN-GelMA with a significant increase in cell number over 21 days (p<0.0001) compared to GelMA alone. HBMSCs-laden LPN-GelMA scaffolds supported osteogenic differentiation evidenced by mineralized nodule formation, including in the absence of the osteogenic drug dexamethasone. Ex vivo implantation in a chick chorioallantoic membrane (CAM) model, demonstrated excellent integration of the bioink constructs in the vascular chick embryo after 7 days of incubation. VEGF-loaded LPN-GelMA constructs demonstrated significantly higher vessel penetration than GelMA-VEGF (p<0.0001) scaffolds. Integration and vascularisation was directly related to increased drug absorption and retention by LPN-GelMA compared to LPN-free GelMA. In summary, a novel light-curable nanocomposite bioink for 3D skeletal regeneration supportive of cell growth and growth factor retention and delivery, evidenced by ex vivo vasculogenesis, was developed with potential application in hard and soft tissue reparation.
1758-5082
Cidonio, Gianluca
558ad583-899a-4d8c-b42b-bc1c354c8757
Alcala Orozco, Cesar Roberto
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Lim, Khoon
17f1bb13-c6cb-4e77-b5d4-1cb5670b7350
Glinka, Michael
7630ab6c-91c5-4840-9c25-12cb61fcb91e
Mutreja, Isha
0d3565ce-c1b8-41f2-8537-0d26aa0108b8
Kim, Yanghee
de0d641b-c2cb-4e73-9ae2-e20d33689f5d
Dawson, Jonathan
b220fe76-498d-47be-9995-92da6c289cf3
Woodfield, Tim
7a3c5071-c961-42fb-b1d8-87816a3ccd27
Oreffo, Richard
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Cidonio, Gianluca
558ad583-899a-4d8c-b42b-bc1c354c8757
Alcala Orozco, Cesar Roberto
0ea3e7de-e838-4621-b6f6-165e69e1c26a
Lim, Khoon
17f1bb13-c6cb-4e77-b5d4-1cb5670b7350
Glinka, Michael
7630ab6c-91c5-4840-9c25-12cb61fcb91e
Mutreja, Isha
0d3565ce-c1b8-41f2-8537-0d26aa0108b8
Kim, Yanghee
de0d641b-c2cb-4e73-9ae2-e20d33689f5d
Dawson, Jonathan
b220fe76-498d-47be-9995-92da6c289cf3
Woodfield, Tim
7a3c5071-c961-42fb-b1d8-87816a3ccd27
Oreffo, Richard
ff9fff72-6855-4d0f-bfb2-311d0e8f3778

Cidonio, Gianluca, Alcala Orozco, Cesar Roberto, Lim, Khoon, Glinka, Michael, Mutreja, Isha, Kim, Yanghee, Dawson, Jonathan, Woodfield, Tim and Oreffo, Richard (2019) Osteogenic and angiogenic tissue formation in high fidelity nanocomposite Laponite-gelatin bioinks. Biofabrication, 11 (3), [035027]. (doi:10.1088/1758-5090/ab19fd).

Record type: Article

Abstract

Bioprinting of living cells is rapidly developing as an advanced biofabrication approach to engineer tissues. Bioinks can be extruded in three-dimensions (3D) to fabricate complex and hierarchical constructs for implantation. However, lack of functionality can often be attributed to poor bioink properties. Indeed, advanced bioinks encapsulating living cells should: (i) present optimal rheological properties and retain 3D structure post-fabrication, (ii) promote cell viability and support cell differentiation, (iii) localise proteins of interest (e.g. vascular endothelial growth factor (VEGF)) to stimulate encapsulated cell activity and tissue ingrowth upon implantation. In this study, we present the results of the inclusion of a synthetic nanoclay, Laponite (LPN) together with a gelatin methacryloyl (GelMA) bioink and the development of a functional cell-instructive bioink. A nanocomposite bioink displaying enhanced shape fidelity retention and interconnected porosity within extrusion-bioprinted fibres was observed. Human bone marrow stromal cell (HBMSC) viability within the nanocomposite showed no significant changes over 21 days of culture in LPN-GelMA (85.60 ± 10.27 %), compared to a significant decrease in GelMA from 7 (95.88 ± 2.90 %) to 21 days (55.54 ± 14.72 %) (p<0.01). HBMSCs were observed to proliferate in LPN-GelMA with a significant increase in cell number over 21 days (p<0.0001) compared to GelMA alone. HBMSCs-laden LPN-GelMA scaffolds supported osteogenic differentiation evidenced by mineralized nodule formation, including in the absence of the osteogenic drug dexamethasone. Ex vivo implantation in a chick chorioallantoic membrane (CAM) model, demonstrated excellent integration of the bioink constructs in the vascular chick embryo after 7 days of incubation. VEGF-loaded LPN-GelMA constructs demonstrated significantly higher vessel penetration than GelMA-VEGF (p<0.0001) scaffolds. Integration and vascularisation was directly related to increased drug absorption and retention by LPN-GelMA compared to LPN-free GelMA. In summary, a novel light-curable nanocomposite bioink for 3D skeletal regeneration supportive of cell growth and growth factor retention and delivery, evidenced by ex vivo vasculogenesis, was developed with potential application in hard and soft tissue reparation.

Text
LPN-GelMA paper_Biofab_ACCEPTED 2019 - Accepted Manuscript
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More information

Accepted/In Press date: 16 April 2019
e-pub ahead of print date: 12 June 2019
Published date: July 2019

Identifiers

Local EPrints ID: 430497
URI: http://eprints.soton.ac.uk/id/eprint/430497
ISSN: 1758-5082
PURE UUID: 5344398b-d7da-4ed1-b184-84390cf07b4e
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: 02 May 2019 16:30
Last modified: 07 Oct 2020 04:33

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