A papain-induced disc degeneration model for the assessment of thermo-reversible hydrogel-cells therapeutic approach

Malonzo, Cherry; Chan, Samantha CW; Kabiri, Azadeh; Eglin, David; Grad, Sybille; Bonel, Harald Marcel; Benneker, Lorin Michael; Gantenbein, Benjamin (2013). A papain-induced disc degeneration model for the assessment of thermo-reversible hydrogel-cells therapeutic approach. Journal of tissue engineering and regenerative medicine, 9(12), E167-E176. John Wiley & Sons 10.1002/term.1667

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Nucleus pulposus (NP) regeneration by the application of injectable cell-embedded hydrogels is an appealing approach for tissue engineering. We investigated a thermo-reversible hydrogel (TR-HG), based on a modified polysaccharide with a thermo-reversible polyamide [poly(N-isopropylacrylamide), pNIPAM], which is made to behave as a liquid at room temperature and hardens at > 32 °C. In order to test the hydrogel, a papain-induced bovine caudal disc degeneration model (PDDM), creating a cavity in the NP, was employed. Human mesenchymal stem cells (hMSCs) or autologous bovine NP cells (bNPCs) were seeded in TR-HG; hMSCs were additionally preconditioned with rhGDF-5 for 7 days. Then, TR-HG was reversed to a fluid and the cell suspension injected into the PDDM and kept under static loading for 7 days. Experimental design was: (D1) fresh disc control + PBS injection; (D2) PDDM + PBS injection; (D3) PDDM + TR-HG (material control); (D4) PDDM + TR-HG + bNPCs; (D5) PDDM + TR-HG + hMSCs. Magnetic resonance imaging performed before and after loading, on days 9 and 16, allowed imaging of the hydrogel-filled PDDM and assessment of disc height and volume changes. In gel-injected discs the NP region showed a major drop in volume and disc height during culture under static load. The RT–PCR results of injected hMSCs showed significant upregulation of ACAN, COL2A1, VCAN and SOX9 during culture in the disc cavity, whereas the gene expression profile of NP cells remained unchanged. The cell viability of injected cells (NPCs or hMSCs) was maintained at over 86% in 3D culture and dropped to ~72% after organ culture. Our results underline the need for load-bearing hydrogels that are also cyto-compatible.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute for Surgical Technology & Biomechanics ISTB
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Orthopaedic Surgery
04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Institute of Diagnostic, Interventional and Paediatric Radiology

UniBE Contributor:

Kabiri, Azadeh; Bonel, Harald Marcel; Benneker, Lorin Michael and Gantenbein, Benjamin

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1932-6254

Publisher:

John Wiley & Sons

Language:

English

Submitter:

Benjamin Gantenbein

Date Deposited:

19 Mar 2014 00:39

Last Modified:

26 Jun 2016 01:47

Publisher DOI:

10.1002/term.1667

PubMed ID:

23303720

URI:

https://boris.unibe.ch/id/eprint/43388

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