Injectable biomaterial induces regeneration of the intervertebral disc in a caprine loaded disc culture model †

SNUGGS, Joseph W., EMANUEL, Kaj S., RUSTENBURG, Christine, JANANI, Ronak, PARTRIDGE, Simon, SAMMON, Christopher, SMIT, Theo H. and LE MAITRE, Christine L. (2023). Injectable biomaterial induces regeneration of the intervertebral disc in a caprine loaded disc culture model †. Biomaterials Science.

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Abstract

Back pain is the leading cause of disability with half of cases attributed to intervertebral disc (IVD) degeneration, yet currently no therapies target this cause. We previously reported an ex vivo caprine loaded disc culture system (LDCS) that accurately represents the cellular phenotype and biomechanical environment of human IVD degeneration. Here, the efficacy of an injectable hydrogel system (LAPONITE® crosslinked pNIPAM-co-DMAc, (NPgel)) to halt or reverse the catabolic processes of IVD degeneration was investigated within the LDCS. Following enzymatic induction of degeneration using 1 mg mL−1 collagenase and 2 U mL−1 chondroitinase ABC within the LDCS for 7 days, IVDs were injected with NPgel alone or with encapsulated human bone marrow progenitor cells (BMPCs). Un-injected caprine discs served as degenerate controls. IVDs were cultured for a further 21 days within the LDCS. Tissues were then processed for histology and immunohistochemistry. No extrusion of NPgel was observed during culture. A significant decrease in histological grade of degeneration was seen in both IVDs injected with NPgel alone and NPgel seeded with BMPCs, compared to un-injected controls. Fissures within degenerate tissue were filled by NPgel and there was evidence of native cell migration into injected NPgel. The expression of healthy NP matrix markers (collagen type II and aggrecan) was increased, whereas the expression of catabolic proteins (MMP3, ADAMTS4, IL-1β and IL-8) was decreased in NPgel (±BMPCs) injected discs, compared to degenerate controls. This demonstrates that NPgel promotes new matrix production at the same time as halting the degenerative cascade within a physiologically relevant testing platform. This highlights the potential of NPgel as a future therapy for IVD degeneration.

Item Type:	Article
Additional Information:	** Embargo end date: 17-05-2023 ** From Royal Society of Chemistry via Jisc Publications Router ** Licence for this article starting on 17-05-2023: http://creativecommons.org/licenses/by/3.0/ ** Acknowledgements: We thank Mark Wilkinson, Diane Swift and South Yorkshire and North Derbyshire Musculoskeletal Biobank for providing surgical samples for BMPCs, and Versus Arthritis and the MRC (MR/P026796/1) for funding this research. **Journal IDs: pissn 2047-4830; eissn 2047-4849 **Article IDs: publisher-id: d3bm00150d **History: published_online 17-05-2023; accepted 07-05-2023; submitted 30-01-2023
Identification Number:	https://doi.org/10.1039/d3bm00150d
SWORD Depositor:	Colin Knott
Depositing User:	Colin Knott
Date Deposited:	19 May 2023 16:26
Last Modified:	11 Oct 2023 14:46
URI:	https://shura.shu.ac.uk/id/eprint/31912

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