An injectable, self-healing and MMP-inhibiting hyaluronic acid gel via iron coordination

GAO, Ziyu, YANG, Xuebin, JONES, Elena, BINGHAM, Paul, SCRIMSHIRE, Alex, THORNTON, Paul and TRONCI, Giuseppe (2020). An injectable, self-healing and MMP-inhibiting hyaluronic acid gel via iron coordination. International Journal of Biological Macromolecules.

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    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 one minute 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 21 the elasticity and biocompatibility requirements for connective tissue application. Significantly enhanced inhibition of MMP-13 activity was achieved after 12 hours 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 % à 81.0±7.5 %), with at least comparable extent to the case of the OSTENIL® PLUS-treated SF group (100.0±17.6 % à 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.

    Item Type: Article
    Uncontrolled Keywords: 0601 Biochemistry and Cell Biology; Polymers
    SWORD Depositor: Symplectic Elements
    Depositing User: Symplectic Elements
    Date Deposited: 12 Oct 2020 10:28
    Last Modified: 12 Oct 2020 10:30
    URI: http://shura.shu.ac.uk/id/eprint/27389

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