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The effect of a heparin-based coacervate of fibroblast growth factor-2 on scarring in the infarcted myocardium

Chu, H and Chen, CW and Huard, J and Wang, Y (2013) The effect of a heparin-based coacervate of fibroblast growth factor-2 on scarring in the infarcted myocardium. Biomaterials, 34 (6). 1747 - 1756. ISSN 0142-9612

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Abstract

Effective delivery of exogenous angiogenic growth factors can provide a new therapy for ischemic diseases. However, clinical translation of growth factor therapies faces multiples challenges; the most significant one is the short half-life of the naked protein. We use heparin and a nontoxic polycation to form an injectable coacervate that protects growth factors and preserves their bioactivities. Here we report the effectiveness of fibroblast growth factor-2 (FGF2) coacervate in reducing scar burden in a mouse myocardial infarction model. The coacervate provides spatial and temporal control of the release of heparin-binding proteins. Coacervate treated animals show lower level of inflammation, fibrosis and cardiomyocyte death in the infarcted myocardium. Histological evaluation indicates that FGF2 coacervate significantly increases the number of endothelial and mural cells and results in stable capillaries and arterioles to at least 6 weeks post injection. Echocardiographic assessment shows that FGF2 coacervate promotes cardiac contractibility and inhibits ventricular dilation, suggesting that the improvement at the tissue level leads to better cardiac functions. On the contrary, identical dosage of free FGF2 shows no statistical difference from saline or vehicle control in histological or functional assessment. Overall, injection of FGF2 coacervate ameliorated the ischemic injury caused by myocardial infarction. The promising data in rodent warrant further examination of the potential of clinical translation of this technology. © 2012 Elsevier Ltd.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Chu, H
Chen, CW
Huard, J
Wang, Yyaw20@pitt.eduYAW20orcid.org/0000-0003-2067-382X
Centers: Other Centers, Institutes, or Units > McGowan Institute for Regenerative Medicine
Date: 1 February 2013
Date Type: Publication
Journal or Publication Title: Biomaterials
Volume: 34
Number: 6
Page Range: 1747 - 1756
DOI or Unique Handle: 10.1016/j.biomaterials.2012.11.019
Schools and Programs: School of Medicine > Orthopaedic Surgery
School of Medicine > Surgery
Swanson School of Engineering > Bioengineering
Swanson School of Engineering > Chemical Engineering
Refereed: Yes
ISSN: 0142-9612
MeSH Headings: Animals; Fibroblast Growth Factor 2--pharmacology; Heparin--chemistry; Heparin--pharmacology; Male; Mice; Mice, Inbred BALB C; Myocardial Infarction--pathology
PubMed ID: 23211448
Date Deposited: 31 Mar 2014 15:21
Last Modified: 25 Jan 2019 21:55
URI: http://d-scholarship.pitt.edu/id/eprint/20829

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