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

TL;DR

This study introduces an injectable, self-healing hyaluronic acid hydrogel that inhibits MMP activity, offering a promising localized treatment approach for osteoarthritis by combining mechanical support with enzyme regulation.

Contribution

The paper presents a novel iron-coordinated HA hydrogel that is rapidly formed, biocompatible, and effectively inhibits MMP activity in vitro and in clinical samples, advancing OA therapy methods.

Findings

Hydrogel forms within one minute at room temperature.

Hydrogel exhibits high shear strain tolerance and biocompatibility.

Significant MMP-13 inhibition observed after 12 hours in vitro and in clinical samples.

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 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.