  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 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 %
--> 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.
