Engineering 3D functional tissue constructs using self-assembling cell-laden microniches.

Xing, D; Liu, W; Li, JJ; Liu, L; Guo, A; Wang, B; Yu, H; Zhao, Y; Chen, Y; You, Z; Lyu, C; Li, W; Liu, A; Du, Y; Lin, J

Engineering 3D functional tissue constructs using self-assembling cell-laden microniches.

Xing, D Liu, W

Li, JJ Liu, L Guo, A Wang, B Yu, H Zhao, Y Chen, Y You, Z Lyu, C Li, W Liu, A Du, Y Lin, J

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Publisher:: ELSEVIER SCI LTD
Publication Type:: Journal Article
Citation:: Acta biomaterialia, 2020, 114, pp. 170-182
Issue Date:: 2020-09

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Field	Value	Language
dc.contributor.author	Xing, D
dc.contributor.author	Liu, W https://orcid.org/0000-0002-3003-1313
dc.contributor.author	Li, JJ
dc.contributor.author	Liu, L
dc.contributor.author	Guo, A
dc.contributor.author	Wang, B
dc.contributor.author	Yu, H
dc.contributor.author	Zhao, Y
dc.contributor.author	Chen, Y
dc.contributor.author	You, Z
dc.contributor.author	Lyu, C
dc.contributor.author	Li, W
dc.contributor.author	Liu, A
dc.contributor.author	Du, Y
dc.contributor.author	Lin, J
dc.date.accessioned	2020-12-28T05:15:12Z
dc.date.available	2020-07-31
dc.date.available	2020-12-28T05:15:12Z
dc.date.issued	2020-09
dc.identifier.citation	Acta biomaterialia, 2020, 114, pp. 170-182
dc.identifier.issn	1742-7061
dc.identifier.issn	1878-7568
dc.identifier.uri	http://hdl.handle.net/10453/144976
dc.description.abstract	Tissue engineering using traditional size fixed scaffolds and injectable biomaterials are faced with many limitations due to the difficulties of producing macroscopic functional tissues. In this study, 3D functional tissue constructs were developed by inducing self-assembly of microniches, which were cell-laden gelatin microcryogels. During self-assembly, the accumulation of extracellular matrix (ECM) components was found to strengthen cell-cell and cell-ECM interactions, leading to the construction of a 'native' microenvironment that better preserved cell viability and functions. MSCs grown in self-assembled constructs showed increased maintenance of stemness, reduced senescence and improved paracrine activity compared with cells grown in individual microniches without self-assembly. As an example of applying the self-assembled constructs in tissue regeneration, the constructs were used to induce in vivo articular cartilage repair and successfully regenerated hyaline-like cartilage tissue in the absence of other extrinsic factors. This unique approach of developing self-assembled 3D functional constructs holds great promise for the generation of tissue engineered organoids and repair of challenging tissue defects. STATEMENT OF SIGNIFICANCE: We developed 3D functional tissue constructs using a unique gelatin-based microscopic hydrogel (microcryogels). Mesenchymal stem cells (MSCs) were loaded into gelatin microcryogels to form microscopic cell-laden units (microniches), which were induced to undergo self-assembly using a specially designed 3D printed frame. Extracellular matrix accumulation among the microniches resulted in self-assembled macroscopic constructs with superior ability to maintain the phenotypic characteristics and stemness of MSCs, together with the suppression of senescence and enhanced paracrine function. As an example of application in tissue regeneration, the self-assembled constructs were shown to successfully repair articular cartilage defects without any other supplements. This unique strategy for developing 3D functional tissue constructs allows the optimisation of stem cell functions and construction of biomimetic tissue organoids.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	ELSEVIER SCI LTD
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT1120249
dc.relation.ispartof	Acta biomaterialia
dc.relation.isbasedon	10.1016/j.actbio.2020.07.058
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject.classification	Biomedical Engineering
dc.title	Engineering 3D functional tissue constructs using self-assembling cell-laden microniches.
dc.type	Journal Article
utslib.citation.volume	114
utslib.location.activity	England
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Strength - AAI - Advanced Analytics Institute Research Centre
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Computer Science
utslib.copyright.status	closed_access	*
dc.date.updated	2020-12-28T05:14:24Z
pubs.publication-status	Published
pubs.volume	114

Abstract:

Tissue engineering using traditional size fixed scaffolds and injectable biomaterials are faced with many limitations due to the difficulties of producing macroscopic functional tissues. In this study, 3D functional tissue constructs were developed by inducing self-assembly of microniches, which were cell-laden gelatin microcryogels. During self-assembly, the accumulation of extracellular matrix (ECM) components was found to strengthen cell-cell and cell-ECM interactions, leading to the construction of a 'native' microenvironment that better preserved cell viability and functions. MSCs grown in self-assembled constructs showed increased maintenance of stemness, reduced senescence and improved paracrine activity compared with cells grown in individual microniches without self-assembly. As an example of applying the self-assembled constructs in tissue regeneration, the constructs were used to induce in vivo articular cartilage repair and successfully regenerated hyaline-like cartilage tissue in the absence of other extrinsic factors. This unique approach of developing self-assembled 3D functional constructs holds great promise for the generation of tissue engineered organoids and repair of challenging tissue defects. STATEMENT OF SIGNIFICANCE: We developed 3D functional tissue constructs using a unique gelatin-based microscopic hydrogel (microcryogels). Mesenchymal stem cells (MSCs) were loaded into gelatin microcryogels to form microscopic cell-laden units (microniches), which were induced to undergo self-assembly using a specially designed 3D printed frame. Extracellular matrix accumulation among the microniches resulted in self-assembled macroscopic constructs with superior ability to maintain the phenotypic characteristics and stemness of MSCs, together with the suppression of senescence and enhanced paracrine function. As an example of application in tissue regeneration, the self-assembled constructs were shown to successfully repair articular cartilage defects without any other supplements. This unique strategy for developing 3D functional tissue constructs allows the optimisation of stem cell functions and construction of biomimetic tissue organoids.

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http://hdl.handle.net/10453/144976