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Biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells

Biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells
Biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells

Autograft or metal implants are routinely used in skeletal repair. However, they fail to provide long-term clinical resolution, necessitating a functional biomimetic tissue engineering alternative. The use of native human bone tissue for synthesizing a biomimetic material ink for three-dimensional (3D) bioprinting of skeletal tissue is an attractive strategy for tissue regeneration. Thus, human bone extracellular matrix (bone-ECM) offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells (HBMSCs) to proliferate and differentiate along the osteogenic lineage. In this study, we engineered a novel material ink (LAB) by blending human bone-ECM (B) with nanoclay (L, Laponite ®) and alginate (A) polymers using extrusion-based deposition. The inclusion of the nanofiller and polymeric material increased the rheology, printability, and drug retention properties and, critically, the preservation of HBMSCs viability upon printing. The composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor (VEGF) enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane (CAM) model. The inclusion of bone morphogenetic protein-2 (BMP-2) with the HBMSCs further enhanced vascularization and mineralization after only seven days. This study demonstrates the synergistic combination of nanoclay with biomimetic materials (alginate and bone-ECM) to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair. Graphic abstract: (Figure presented.)

3D bioprinting, Bone, Extracellular matrix, Nanoclay
121-136
Kim, Yang-Hee
de0d641b-c2cb-4e73-9ae2-e20d33689f5d
Kanczler, Janos M.
eb8db9ff-a038-475f-9030-48eef2b0559c
Lanham, Stuart
28fdbbef-e3b6-4fdf-bd0f-4968eeb614d6
Rawlings, Andrew
f7d578ff-a012-4f84-b91f-097736b1f483
Cidonio, Gianluca
558ad583-899a-4d8c-b42b-bc1c354c8757
Dawson, Jon
b220fe76-498d-47be-9995-92da6c289cf3
Oreffo, Richard
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
et al.
Kim, Yang-Hee
de0d641b-c2cb-4e73-9ae2-e20d33689f5d
Kanczler, Janos M.
eb8db9ff-a038-475f-9030-48eef2b0559c
Lanham, Stuart
28fdbbef-e3b6-4fdf-bd0f-4968eeb614d6
Rawlings, Andrew
f7d578ff-a012-4f84-b91f-097736b1f483
Cidonio, Gianluca
558ad583-899a-4d8c-b42b-bc1c354c8757
Dawson, Jon
b220fe76-498d-47be-9995-92da6c289cf3
Oreffo, Richard
ff9fff72-6855-4d0f-bfb2-311d0e8f3778

Kim, Yang-Hee, Kanczler, Janos M. and Lanham, Stuart , et al. (2024) Biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells. Bio-Design and Manufacturing, 7 (2), 121-136. (doi:10.1007/s42242-023-00265-z).

Record type: Article

Abstract

Autograft or metal implants are routinely used in skeletal repair. However, they fail to provide long-term clinical resolution, necessitating a functional biomimetic tissue engineering alternative. The use of native human bone tissue for synthesizing a biomimetic material ink for three-dimensional (3D) bioprinting of skeletal tissue is an attractive strategy for tissue regeneration. Thus, human bone extracellular matrix (bone-ECM) offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells (HBMSCs) to proliferate and differentiate along the osteogenic lineage. In this study, we engineered a novel material ink (LAB) by blending human bone-ECM (B) with nanoclay (L, Laponite ®) and alginate (A) polymers using extrusion-based deposition. The inclusion of the nanofiller and polymeric material increased the rheology, printability, and drug retention properties and, critically, the preservation of HBMSCs viability upon printing. The composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor (VEGF) enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane (CAM) model. The inclusion of bone morphogenetic protein-2 (BMP-2) with the HBMSCs further enhanced vascularization and mineralization after only seven days. This study demonstrates the synergistic combination of nanoclay with biomimetic materials (alginate and bone-ECM) to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair. Graphic abstract: (Figure presented.)

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Accepted/In Press date: 13 December 2023
e-pub ahead of print date: 5 March 2024
Published date: 5 March 2024
Additional Information: This study was supported by grants from the Biotechnology and Biological Sciences Research Council (Nos. BBSRC LO21071/ and BB/L00609X/1) and UK Regenerative Medicine Platform Hub Acellular Approaches for Therapeutic Delivery (No. MR/K026682/1), Acellular Hub, SMART Materials 3D Architecture (No. MR/R015651/1), and the UK Regenerative Medicine Platform (No. MR/L012626/1 Southampton Imaging) to ROCO and MRC-AMED Regenerative Medicine and Stem Cell Research Initiative (No. MR/ V00543X/1) to JID, ROCO and YHK. GC acknowledges funding from AIRC Aldi Fellowship under grant agreement No. 25412. Publisher Copyright: © The Author(s) 2024.
Keywords: 3D bioprinting, Bone, Extracellular matrix, Nanoclay

Identifiers

Local EPrints ID: 487989
URI: http://eprints.soton.ac.uk/id/eprint/487989
PURE UUID: 547151e8-d4a3-46f4-bbd4-27d26c83d1ae
ORCID for Yang-Hee Kim: ORCID iD orcid.org/0000-0002-5312-3448
ORCID for Janos M. Kanczler: ORCID iD orcid.org/0000-0001-7249-0414
ORCID for Stuart Lanham: ORCID iD orcid.org/0000-0002-4516-264X
ORCID for Jon 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: 12 Mar 2024 17:40
Last modified: 15 Aug 2024 01:47

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Contributors

Author: Yang-Hee Kim ORCID iD
Author: Janos M. Kanczler ORCID iD
Author: Stuart Lanham ORCID iD
Author: Andrew Rawlings
Author: Gianluca Cidonio
Author: Jon Dawson ORCID iD
Author: Richard Oreffo ORCID iD
Corporate Author: et al.

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