Gao, Z orcid.org/0000-0003-2808-0826, Yang, X orcid.org/0000-0002-0144-2826, Jones, E orcid.org/0000-0001-9365-2283 et al. (4 more authors) (2020) An injectable, self-healing and MMP-inhibiting hyaluronic acid gel via iron coordination. International Journal of Biological Macromolecules, 165 (B). pp. 2022-2029. ISSN 0141-8130
Abstract
Regulating the activity of matrix metalloproteinases (MMPs) is a potential strategy for osteoarthritis (OA) therapy, although delivering this effect in a spatially and temporally localised fashion remains a challenge. Here, we report an injectable and self-healing hydrogel enabling factor-free MMP regulation and biomechanical competence in situ. The hydrogel is realised within 1 min upon room temperature coordination between hyaluronic acid (HA) and a cell-friendly iron-glutathione complex in aqueous environment. The resultant gel displayed up to 300% in shear strain and tolerance towards ATDC 5 chondrocytes, in line with the elasticity and biocompatibility requirements for connective tissue application. Significantly enhanced inhibition of MMP-13 activity was achieved after 12 h in vitro, compared with a commercial HA injection (OSTENIL® PLUS). Noteworthy, 24-hour incubation of a clinical synovial fluid sample collected from a late-stage OA patient with the reported hydrogel was still shown to downregulate synovial fluid MMP activity (100.0 ± 17.6% ➔ 81.0 ± 7.5%), with at least comparable extent to the case of the OSTENIL® PLUS-treated SF group (100.0 ± 17.6% ➔ 92.3 ± 27.3%). These results therefore open up new possibilities in the use of HA as both mechanically-competent hydrogel as well as a mediator of MMP regulation for OA therapy.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020, Elsevier B.V. All rights reserved. This is an author produced version of an article published in International Journal of Biological Macromolecules. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Hyaluronic acid; Iron-glutathione complex; Injectable hydrogel; Synovial fluid; Osteoarthritis; MMP-13 inhibition |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Colour Science (Leeds) The University of Leeds > Faculty of Arts, Humanities and Cultures (Leeds) > School of Design (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Dentistry (Leeds) > Oral Biology (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Experimental Musculoskeletal Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 15 Oct 2020 10:34 |
Last Modified: | 17 Oct 2021 00:38 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.ijbiomac.2020.10.079 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:166544 |