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Title: Three-dimensional hypoxic culture of human mesenchymal stem cells encapsulated in a photocurable, biodegradable polymer hydrogel: a potential injectable cellular product for nucleus pulposus regeneration
Authors: Kumar, Deepak
Gerges, Irini
Tamplenizza, Margherita
Lenardi, Cristina
Forsyth, Nicholas R.
Liu, Yang
Keywords: Chondrogenic differentiation
Encapsulation
Hypoxia
Mesenchymal stem cells
Photocurable hydrogels
Issue Date: 2014
Publisher: Elsevier / © Acta Materialia Inc.
Citation: KUMAR, D. ... et al, 2014. Three-dimensional hypoxic culture of human mesenchymal stem cells encapsulated in a photocurable, biodegradable polymer hydrogel: a potential injectable cellular product for nucleus pulposus regeneration. Acta Biomaterialia, 10 (8), pp. 3463-3474.
Abstract: Nucleus pulposus (NP) tissue damage can induce detrimental mechanical stresses and strains on the intervertebral disc, leading to disc degeneration. This study demonstrates the potential of a novel, photo-curable, injectable, synthetic polymer hydrogel (pHEMA-co-APMA grafted with polyamidoamine (PAA)) to encapsulate and differentiate human mesenchymal stem cells (hMSC) towards a NP phenotype under hypoxic conditions which could be used to restore NP tissue function and mechanical properties. Encapsulated hMSC cultured in media (hMSC and chondrogenic) displayed good cell viability up to day 14. The genotoxicity effects of ultraviolet (UV) on hMSC activity confirmed the acceptability of 2.5min of UV light exposure to cells. Cytotoxicity investigations revealed that hMSC cultured in media containing p(HEMA-co-APMA) grafted with PAA degradation product (10% and 20%v/v concentration) for 14days significantly decreased the initial hMSC adhesion ability and proliferation rate from 24h to day 14. Successful differentiation of encapsulated hMSC within hydrogels towards chondrogenesis was observed with elevated expression levels of aggrecan and collagen II when cultured in chondrogenic media under hypoxic conditions, in comparison with culture in hMSC media for 14days. Characterization of the mechanical properties revealed a significant decrease in stiffness and modulus values of cellular hydrogels in comparison with acellular hydrogels at both day 7 and day 14. These results demonstrate the potential use of an in vivo photo-curable injectable, synthetic hydrogel with encapsulated hMSC for application in the repair and regeneration of NP tissue.
Description: This is an Open Access Article. It is published by Elsevier under the Creative Commons Attribution 3.0 Unported Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/3.0/
Sponsor: This work was supported by the EPSRC [grant number EP/H028277/1].
Version: Published
DOI: 10.1016/j.actbio.2014.04.027
URI: https://dspace.lboro.ac.uk/2134/14591
Publisher Link: http://dx.doi.org/10.1016/j.actbio.2014.04.027
Appears in Collections:Published Articles (Mechanical, Electrical and Manufacturing Engineering)

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