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

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 (R) PLUS). Noteworthy, 24hour incubation of a clinical synovial fluid sample collected froma late-stage OA patientwith 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 (R) 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. (C) 2020 Elsevier B.V. All rights reserved.