Research ArticlesBIOMATERIALS

Local Hydrogel Release of Recombinant TIMP-3 Attenuates Adverse Left Ventricular Remodeling After Experimental Myocardial Infarction

Science Translational Medicine  12 Feb 2014:
Vol. 6, Issue 223, pp. 223ra21
DOI: 10.1126/scitranslmed.3007244

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Hydrogel-Inhibitor Combo Stops Heart Damage

After a heart attack, or myocardial infarction (MI), the heart tries to repair itself. This natural process is well intentioned but results in infarct expansion, scar formation, and, in turn, reduced heart function. To prevent such adverse remodeling, Eckhouse and colleagues designed an injectable hydrogel that inhibits the activity of enzymes directly involved in tissue repair.

Matrix metalloproteinases (MMPs) are enzymes that are activated in heart tissue after MI. The authors encapsulated TIMP-3 (tissue inhibitor of metalloproteinase 3) in hyaluronic acid hydrogels. The gel/TIMP-3 combo or a control gel without the inhibitor was injected into the hearts of pigs after a heart attack. Weeks later, heart function, inflammation, and remodeling were evaluated. Animals administered the hydrogel with TIMP-3 had improved heart function [as determined by the left ventricular ejection fraction (LVEF)], improved LV geometry, and reduced infarct size. This local delivery mechanism could be used in the context of surgery, such as during coronary revascularization after a heart attack. Because it has been tested in pigs—which have similar heart anatomy to humans—and because other hydrogels, like alginate, have been tested in the human heart before, it is possible that this gel-inhibitor combination therapy could advance to clinical trials in the near future.