Journal
ACTA BIOMATERIALIA
Volume 36, Issue -, Pages 99-111Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2016.03.029
Keywords
Intervertebral disc; Injectable hydrogel; Nucleus Pulposus; Mesenchymal stem cells
Funding
- Biomolecular Sciences Research Centre, Sheffield Hallam University
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There is an urgent need for new therapeutic options for low back pain, which target degeneration of the intervertebral disc (IVD). Here, we investigated a pNIPAM hydrogel system, which is liquid at 39 degrees C ex vivo, where following injection into the IVD, body temperature triggers gelation. The combined effects of hypoxia (5% O-2) and the structural environment of the hydrogel delivery system on the differentiation of human mesenchymal stem cells (hMSCs), towards an NP cell phenotype was investigated. hMSCs were incorporated into the liquid hydrogel, the mixture solidified and cultured for up to 6 weeks under 21% O-2 or 5% O-2 where viability was maintained. Immunohistochemistry revealed significant increases in NP matrix components: aggrecan; collagen type II and chondroitin sulphate after culture for 1 week in 5% O-2, accompanied by increased matrix staining for proteoglycans and collagen, observed histologically. NP markers HIF1 alpha, PAX1 and FOXF1 were also significantly increased where hMSC were incorporated into hydrogels with accelerated expression observed when cultured in 5% O-2. hMSCs cultured under hypoxic conditions, which mimic the native disc microenvironment, accelerate differentiation of hMSCs within the hydrogel system, towards the NP phenotype without the need for chondrogenic inducing medium or additional growth factors, thus simplifying the treatment strategy for the repair of IVD degeneration. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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