An injectable hydrogel incorporating mesenchymal precursor cells and pentosan polysulphate for intervertebral disc regeneration

Frith, Jessica E., Cameron, Andrew R., Menzies, Donna J., Ghosh, Peter, Whitehead, Darryl L., Gronthos, Stan, Zannettino, Andrew C.W. and Cooper-White, Justin J. (2013) An injectable hydrogel incorporating mesenchymal precursor cells and pentosan polysulphate for intervertebral disc regeneration. Biomaterials, 34 37: 9430-9440. doi:10.1016/j.biomaterials.2013.08.072


Author Frith, Jessica E.
Cameron, Andrew R.
Menzies, Donna J.
Ghosh, Peter
Whitehead, Darryl L.
Gronthos, Stan
Zannettino, Andrew C.W.
Cooper-White, Justin J.
Title An injectable hydrogel incorporating mesenchymal precursor cells and pentosan polysulphate for intervertebral disc regeneration
Journal name Biomaterials   Check publisher's open access policy
ISSN 0142-9612
1878-5905
Publication date 2013-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.biomaterials.2013.08.072
Volume 34
Issue 37
Start page 9430
End page 9440
Total pages 11
Place of publication Amsterdam, The Netherlands
Publisher Elsevier BV
Collection year 2014
Language eng
Subject 2502 Biomaterials
1502 Banking, Finance and Investment
2503 Ceramics and Composites
2211 Mechanics of Materials
1304 Biophysics
Abstract Intervertebral disc (IVD) degeneration is one of the leading causes of lower back pain and a major health problem worldwide. Current surgical treatments include excision or immobilisation, with neither approach resulting in the repair of the degenerative disc. As such, a tissue engineering-based approach in which stem cells, coupled with an advanced delivery system, could overcome this deficiency and lead to a therapy that encourages functional fibrocartilage generation in the IVD. In this study, we have developed an injectable hydrogel system based on enzymatically-crosslinked polyethylene glycol and hyaluronic acid. We examined the effects of adding pentosan polysulphate (PPS), a synthetic glycosaminoglycan-like factor that has previously been shown (invitro and invivo) to this gel system in order to induce chondrogenesis in mesnchymal precursor cells (MPCs) when added as a soluble factor, even in the absence of additional growth factors such as TGF-β. We show that both the gelation rate and mechanical strength of the resulting hydrogels can be tuned in order to optimise the conditions required to produce gels with the desired combination of properties for an IVD scaffold. Human immunoselected STRO-1+ MPCs were then incorporated into the hydrogels. They were shown to retain good viability after both the initial formation of the gel and for longer-term culture periods invitro. Furthermore, MPC/hydrogel composites formed cartilage-like tissue which was significantly enhanced by the incorporation of PPS into the hydrogels, particularly with respect to the deposition of type-II-collagen. Finally, using a wild-type rat subcutaneous implantation model, we examined the extent of any immune reaction and confirmed that this matrix is well tolerated by the host. Together these data provide evidence that such a system has significant potential as both a delivery vehicle for MPCs and as a matrix for fibrocartilage tissue engineering applications.
Keyword Fibrocartilage
Hydrogel
Mesenchymal progenitor cell
Nucleus pulposus
Pentosan polysulphate
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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