Snuggs, J.W. orcid.org/0000-0002-0200-4596, Emanuel, K.S. orcid.org/0000-0002-4970-4303, Rustenburg, C. orcid.org/0000-0003-1779-2641 et al. (5 more authors) (2023) Injectable biomaterial induces regeneration of the intervertebral disc in a caprine loaded disc culture model. Biomaterials Science, 11 (13). pp. 4630-4643. ISSN 2047-4830
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Royal Society of Chemistry 2023. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence 3.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/3.0/ |
Keywords: | Stem Cell Research; Clinical Research; Biotechnology; Bioengineering; Regenerative Medicine; Chronic Pain; Pain Research; Cellular and gene therapies; Aetiology; Development of treatments and therapeutic interventions; Biological and endogenous factors; Musculoskeletal |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 23 May 2023 08:51 |
Last Modified: | 03 Oct 2024 14:16 |
Status: | Published |
Publisher: | Royal Society of Chemistry (RSC) |
Refereed: | Yes |
Identification Number: | 10.1039/d3bm00150d |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:199426 |