Intervening to Preserve Function in Ischemic Cardiomyopathy with a Porous Hydrogel and Extracellular Matrix Composite in a Rat Myocardial Infarction Model

Yasunari Hayashi; Taro Fujii; Seungil Kim; Takahiro Ozeki; Stephen F Badylak; Antonio D'Amore; Masato Mutsuga; William R Wagner

doi:10.1002/adhm.202402757

Intervening to Preserve Function in Ischemic Cardiomyopathy with a Porous Hydrogel and Extracellular Matrix Composite in a Rat Myocardial Infarction Model

Adv Healthc Mater. 2024 Nov 3:e2402757. doi: 10.1002/adhm.202402757. Online ahead of print.

Authors

Yasunari Hayashi^{1

2

3}, Taro Fujii^{1

2

3}, Seungil Kim^{1

4

5}, Takahiro Ozeki^{1

2

3}, Stephen F Badylak^{1

2

4}, Antonio D'Amore^{1

2

4

6}, Masato Mutsuga³, William R Wagner^{1

2

4

7}

Affiliations

¹ McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, 15219, USA.
² Department of Surgery, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
³ Department of Cardiac Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 4668550, Japan.
⁴ Departments of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
⁵ Department of Agricultural and Biological Engineering, Mississippi State University, MS, 39762, USA.
⁶ Fondazione RiMED, Palermo, 90133, Italy.
⁷ Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA, 15213, USA.

PMID: 39491520
DOI: 10.1002/adhm.202402757

Abstract

Multiple hydrogels are developed for injection therapy after myocardial infarction, with some incorporating substances promoting tissue regeneration and others emphasizing mechanical effects. In this study, porosity and extracellular matrix-derived digest (ECM) are incorporated, into a mechanically optimized, thermoresponsive, degradable hydrogel (poly(N-isopropylacrylamide-co-N-vinylpyrrolidone-co-MAPLA)) and evaluate whether this biomaterial injectate can abrogate adverse remodeling in rat ischemic cardiomyopathy. After myocardial infarction, rats are divided into four groups: NP (non-porous hydrogel) without either ECM or porosity, PM (porous hydrogel) from the same synthetic copolymer with mannitol beads as porogens, and PME with porosity and ECM digest added to the synthetic copolymer. PBS injection alone is a control group. Intramyocardial injections occurred 3 days after myocardial infarction followed by serial echocardiography and histological assessments 8 weeks after infarction. Echocardiographic function and neovascularization improved in the PME group compared to the other hydrogels and PBS injection. The PME group also demonstrated improved LV geometry and macrophage polarization (toward M2) compared to PBS, whereas differences are not observed in the NP or PM groups versus control. These results demonstrate further functional improvement may be achieved in hydrogel injection therapy for ischemic cardiomyopathy by incorporating porosity and ECM digest, representing combined mechanical and biological effects.

Keywords: extracellular matrix; hydrogel; myocardial infarction; porous structure.