The induction of matrix metalloproteinases (MMPs) and subsequent extracellular matrix breakdown is a significant adverse tissue remodeling process that occurs following a myocardial infarction (MI).  One approach to attenuate matrix breakdown therapeutically is through the delivery of tissue inhibitors of MMPs (i.e., TIMP-3).  Since systemic levels of MMP inhibitors have dangerous off-target effects, MMP-triggered release of TIMP-3 would facilitate on-demand release of MMP inhibitors in regions of MMP activity.  In this report, we developed hyaluronic acid (HA) hydrogels containing MMP-sensitive crosslinks where the presence of MMPs controls gel degradation and coincident release of encapsulated TIMP-3 for local MMP inhibition.  These gels form by mixing an aldehyde modified HA with a hydrazide modified HA, where the latter contains an MMP degradable peptide, to form gels in situ without the use of free-radical initiators.  This hydrogel system represents a novel advance towards translating MMP-inhibiting therapeutics to treat MI.

Protease triggered release of molecules from MMP-sensitive hyaluronic acid hydrogels

244th National Meeting (2012)

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