Shear-Thinning Hydrogel for Delayed Delivery of a Small Molecule Metalloproteinase Inhibitor Attenuates Myocardial Infarction Remodeling

Joshua E Mealy; William M Torres; Lisa A Freeburg; Shayne C Barlow; Alison A Whalen; Chima V Maduka; Tarek M Shazly; Jason A Burdick; Francis G Spinale

doi:10.1016/j.jacbts.2024.11.009

Shear-Thinning Hydrogel for Delayed Delivery of a Small Molecule Metalloproteinase Inhibitor Attenuates Myocardial Infarction Remodeling

JACC Basic Transl Sci. 2025 Apr;10(4):458-472. doi: 10.1016/j.jacbts.2024.11.009. Epub 2025 Jan 29.

Authors

Joshua E Mealy¹, William M Torres², Lisa A Freeburg³, Shayne C Barlow³, Alison A Whalen³, Chima V Maduka⁴, Tarek M Shazly⁵, Jason A Burdick⁶, Francis G Spinale⁷

Affiliations

¹ Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
² College of Engineering and Computing, University of South Carolina, Columbia, South Carolina, USA; Cardiovascular Translational Research Center, University of South Carolina School of Medicine, Columbia, South Carolina, USA.
³ Cardiovascular Translational Research Center, University of South Carolina School of Medicine, Columbia, South Carolina, USA.
⁴ BioFrontiers Institute and Department of Chemical and Biological Engineering, University of Colorado-Boulder, Boulder, Colorado, USA.
⁵ College of Engineering and Computing, University of South Carolina, Columbia, South Carolina, USA.
⁶ Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA; BioFrontiers Institute and Department of Chemical and Biological Engineering, University of Colorado-Boulder, Boulder, Colorado, USA.
⁷ College of Engineering and Computing, University of South Carolina, Columbia, South Carolina, USA; Cardiovascular Translational Research Center, University of South Carolina School of Medicine, Columbia, South Carolina, USA; Columbia VA Health Care Center, Columbia, South Carolina, USA. Electronic address: cvctrc@uscmed.sc.edu.

Abstract

Strategic delivery of hydrogels to the newly formed myocardial infarction (MI) is an area of active investigation and offers high target specificity for releasing a small molecule therapeutic payload. This study examined the effects of delayed post-MI delivery (pigs, 3 days post-MI) of a shear-thinning hydrogel which encapsulated and released a small molecule matrix metalloproteinase inhibitor. The results demonstrated the feasibility and efficacy of targeted delivery of a shear-thinning injectable hydrogel containing a small molecule matrix metalloproteinase inhibitor to attenuate post-MI remodeling.

Keywords: extracellular remodelling; matrix metalloproteinase; ventricular function and failure.

Abstract

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