Engineered resveratrol-loaded fibrous scaffolds promotes functional cardiac repair and regeneration through Thioredoxin-1 mediated VEGF pathway

Jacob D Campbell; Rajesh Lakshmanan; Vaithinathan Selvaraju; Diego Accorsi; David W McFadden; Nilanjana Maulik; Mahesh Thirunavukkarasu

doi:10.1016/j.ijpharm.2021.120236

Engineered resveratrol-loaded fibrous scaffolds promotes functional cardiac repair and regeneration through Thioredoxin-1 mediated VEGF pathway

Int J Pharm. 2021 Mar 15:597:120236. doi: 10.1016/j.ijpharm.2021.120236. Epub 2021 Feb 1.

Authors

Jacob D Campbell¹, Rajesh Lakshmanan¹, Vaithinathan Selvaraju¹, Diego Accorsi², David W McFadden³, Nilanjana Maulik⁴, Mahesh Thirunavukkarasu⁵

Affiliations

¹ Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, Farmington 06030, CT, USA; Department of Surgery, University of Connecticut Health, Farmington 06030, CT, USA.
² Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, Farmington 06030, CT, USA; Department of Surgery, University of Connecticut Health, Farmington 06030, CT, USA; Stanley J. Dudrick, Department of Surgery, Saint Mary's Hospital, Waterbury 06706, CT, USA.
³ Department of Surgery, University of Connecticut Health, Farmington 06030, CT, USA.
⁴ Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, Farmington 06030, CT, USA; Department of Surgery, University of Connecticut Health, Farmington 06030, CT, USA. Electronic address: nmaulik@uchc.edu.
⁵ Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, Farmington 06030, CT, USA; Department of Surgery, University of Connecticut Health, Farmington 06030, CT, USA. Electronic address: mthirunavukkarasu@uchc.edu.

PMID: 33539996
DOI: 10.1016/j.ijpharm.2021.120236

Abstract

Despite recent advancements, mortality due to coronary heart disease (CHD) remains high. Recently, the use of tissue-engineered grafts and scaffolds has emerged as a candidate for supporting the myocardium after an ischemic event. Resveratrol is a naturally occurring plant-based non-flavonoid polyphenolic compound found in many natural foods, including grapes and red wine. We embedded resveratrol in a polycaprolactone (PCL) scaffold and evaluated the cardio-therapeutic effects in a murine model of myocardial infarction (MI), with animals being grouped into Sham (S), Myocardial Infarction (MI), MI + PCL, and MI + PCL-Resveratrol (MI + PCL-R). After 4 and 8 weeks, echocardiography was performed to assess ejection fraction (EF) and fractional shortening (FS), which was followed by immunohistochemistry and immunofluorescence analysis at 8 weeks. The MI + PCL-R group showed a significant improvement in EF and FS compared with the MI + PCL group at 4 and 8-weeks post-surgery. PCL-R scaffolds treated hearts revealed decreased inflammatory cell infiltration, improved collagen extracellular matrix (ECM) secretion and blood vessel network formation following MI. The immunofluorescence analysis revealed resveratrol-loaded scaffolds promote increased expression of cTnT, Cx-43, Trx-1, and VEGF proteins. This study reports resveratrol-mediated rescue of ischemic myocardium when delivered through a biodegradable polymeric scaffold system after MI.

Keywords: Acute myocardial ischemia; Angiogenesis; Cardiac regeneration; Resveratrol; Trx-1.

MeSH terms

Animals
Mice
Myocardial Infarction* / drug therapy
Myocardium
Regeneration
Resveratrol
Thioredoxins
Vascular Endothelial Growth Factor A*

Substances

Txn1 protein, mouse
Vascular Endothelial Growth Factor A
vascular endothelial growth factor A, mouse
Thioredoxins
Resveratrol