Dual Delivery of Hepatocyte and Vascular Endothelial Growth Factors via a Protease-Degradable Hydrogel Improves Cardiac Function in Rats

• Type of Material: Article
• Authors: Apoorva S. Salimath, Georgia Institute of Technology; Edward A. Phelps, Georgia Institute of Technology; Archana V. Boopathy, Georgia Institute of Technology; Pao-lin Che, Emory University; Milton Brown, Emory University; Andres J. Garcia, Georgia Institute of Technology; Michael Davis, Emory University
• Language: English
• Date: 2012-11-30
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Salimath et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0050980
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 7
• Issue: 11
• Start Page: e50980
• End Page: e50980
• Grant/Funding Information: Additionally, funding was received in the form of an American Heart Association (AHA) fellowship, National Science Foundation (NSF) Center Grant (CBET-0939511), and Georgia Tech/Emory Center for the Engineering of Living Tissues.; This work was supported by a contract from the National Heart, Lung, and Blood Institute (NHLBI) (HHSN268201000043C) as part of a Program of Excellence in Nanotechnology.
• Keywords: PEPTIDE NANOFIBERS; ANGIOGENESIS; Science & Technology - Other Topics; ENGINEERED PEG HYDROGELS; STEM-CELLS; IN-VITRO; Multidisciplinary Sciences; MULTIDISCIPLINARY SCIENCES; Science & Technology; PROGENITOR CELLS; ACUTE MYOCARDIAL-INFARCTION; INTRAMYOCARDIAL INJECTION; CELL THERAPY; ALGINATE BIOMATERIAL
• Research Categories: Engineering, Mechanical; Health Sciences, Medicine and Surgery; Engineering, Biomedical

Abstract

Acute myocardial infarction (MI) caused by ischemia and reperfusion (IR) is the most common cause of cardiac dysfunction due to local cell death and a temporally regulated inflammatory response. Current therapeutics are limited by delivery vehicles that do not address spatial and temporal aspects of healing. The aim of this study was to engineer biotherapeutic delivery materials to harness endogenous cell repair to enhance myocardial repair and function. We have previously engineered poly(ethylene glycol) (PEG)-based hydrogels to present cell adhesive motifs and deliver VEGF to promote vascularization in vivo. In the current study, bioactive hydrogels with a protease-degradable crosslinker were loaded with hepatocyte and vascular endothelial growth factors (HGF and VEGF, respectively) and delivered to the infarcted myocardium of rats. Release of both growth factors was accelerated in the presence of collagenase due to hydrogel degradation. When delivered to the border zones following ischemia-reperfusion injury, there was no acute effect on cardiac function as measured by echocardiography. Over time there was a significant increase in angiogenesis, stem cell recruitment, and a decrease in fibrosis in the dual growth factor delivery group that was significant compared with single growth factor therapy. This led to an improvement in chronic function as measured by both invasive hemodynamics and echocardiography. These data demonstrate that dual growth factor release of HGF and VEGF from a bioactive hydrogel has the capacity to significantly improve cardiac remodeling and function following IR injury.