Intramyocardial Hydrogel Delivery Decreases Left Ventricular Remodeling and Increases Angiogenesis Post Myocardial Infarction

Inga H Melvinsdottir^{1

2}, Dan Midgett³, Shin Rong Lee⁴, Stephanie L Thorn^{1

2}, Selen Uman⁵, Ricardo Avendano^{1

2}, Taras Lysyy⁶, Fatema Tuj Zohora^{1

2}, Kevin Chen², Marina Mamarian², James S Duncan^{7

8}, Francis G Spinale⁹, Jason A Burdick^{5

10}, Albert J Sinusas^{1

2

7

8}

Affiliations

¹ Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, CT. (I.H.M., S.L.T., R.A., F.T.Z., A.J.S.).
² Department of Internal Medicine, Yale Translational Research Imaging Center, Yale University, New Haven, CT. (I.H.M., S.L.T., R.A., F.T.Z., K.C., M.M., A.J.S.).
³ Johns Hopkins Applied Physics Laboratory, Johns Hopkins University, Laurel, MD (D.M.).
⁴ Department of General Surgery , Yale University, New Haven, CT. (S.R.L.).
⁵ Department of Bioengineering, University of Pennsylvania, Philadelphia (S.U., J.A.B.).
⁶ Section of Transplantation and Immunology, Department of Surgery, Yale University, New Haven, CT. (T.L.).
⁷ Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT. (J.S.D., A.J.S.).
⁸ School of Medicine, and Department of Biomedical Engineering, Yale University, New Haven, CT. (J.S.D., A.J.S.).
⁹ Department of Cell Biology and Anatomy and Cardiovascular Research Center, University of South Carolina School of Medicine and the Columbia VA Health Care System (F.G.S.).
¹⁰ BioFrontiers Institute and Department of Chemical and Biological Engineering, University of Colorado Boulder (J.A.B.).

PMID: 41017463
DOI: 10.1161/CIRCIMAGING.125.018357

Intramyocardial Hydrogel Delivery Decreases Left Ventricular Remodeling and Increases Angiogenesis Post Myocardial Infarction

Inga H Melvinsdottir et al. Circ Cardiovasc Imaging. 2025.

. 2025 Sep 29:e018357.

doi: 10.1161/CIRCIMAGING.125.018357. Online ahead of print.

Authors

Affiliations

¹ Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, CT. (I.H.M., S.L.T., R.A., F.T.Z., A.J.S.).
² Department of Internal Medicine, Yale Translational Research Imaging Center, Yale University, New Haven, CT. (I.H.M., S.L.T., R.A., F.T.Z., K.C., M.M., A.J.S.).
³ Johns Hopkins Applied Physics Laboratory, Johns Hopkins University, Laurel, MD (D.M.).
⁴ Department of General Surgery , Yale University, New Haven, CT. (S.R.L.).
⁵ Department of Bioengineering, University of Pennsylvania, Philadelphia (S.U., J.A.B.).
⁶ Section of Transplantation and Immunology, Department of Surgery, Yale University, New Haven, CT. (T.L.).
⁷ Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT. (J.S.D., A.J.S.).
⁸ School of Medicine, and Department of Biomedical Engineering, Yale University, New Haven, CT. (J.S.D., A.J.S.).
⁹ Department of Cell Biology and Anatomy and Cardiovascular Research Center, University of South Carolina School of Medicine and the Columbia VA Health Care System (F.G.S.).
¹⁰ BioFrontiers Institute and Department of Chemical and Biological Engineering, University of Colorado Boulder (J.A.B.).

PMID: 41017463
DOI: 10.1161/CIRCIMAGING.125.018357

Abstract

Background: Intramyocardial injection of hydrogel into myocardial infarction (MI) areas can reduce left ventricular remodeling and potentially increase angiogenesis post-MI. The radiotracer ^99mTc-Maraciclatide binds to activated αvβ3-integrin, a key factor in angiogenesis, and can be used to evaluate myocardial angiogenesis. This study used multimodality imaging to assess the effects of imageable intramyocardial hydrogel delivery on left ventricular remodeling and angiogenesis after MI.

Methods: Fourteen pigs (N=14) underwent 90 minutes of balloon occlusion and reperfusion. Five days post-MI, they were randomized to receive either intramyocardial hydrogel (n=8) or control saline injections (n=6). Contrast cine-computed tomography was used to assess biomechanical changes before and after treatment (day 1, day 5, and day 12). ^99mTc-Maraciclatide uptake was measured with gamma well counting. Scar burden and angiogenesis were evaluated through histology.

Results: Both groups initially showed a decrease in ejection fraction and an increase in end-diastolic volume post-MI. Hydrogel delivery on day 5 led to a reduction in end-diastolic volume and improvement in left ventricular ejection fraction by day 12. The hydrogel group also exhibited decreased compensatory radial strain in remote myocardial segments, but decreased strain in the hydrogel myocardial segments. There was increased uptake of ^99mTc-maraciclatide in the infarct segments after hydrogel delivery, associated with increased αvβ3-integrin and factor VIII expression in the hydrogel treatment group on histology. However, there was no difference in regional inflammation or scar size between the groups.

Conclusions: Intramyocardial delivery of hydrogel early post-MI resulted in decreased left ventricular remodeling and increased αvβ3-integrin activation associated with an increase in angiogenesis.

Keywords: angiogenesis; hydrogels; multimodal imaging; myocardial infarction; tomography.

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Intramyocardial Hydrogel Delivery Decreases Left Ventricular Remodeling and Increases Angiogenesis Post Myocardial Infarction

Affiliations

Intramyocardial Hydrogel Delivery Decreases Left Ventricular Remodeling and Increases Angiogenesis Post Myocardial Infarction

Authors

Affiliations

Abstract

LinkOut - more resources

Full Text Sources