Copyright © 2007, European Society of Cardiology
Angiogenic effects of sequential release of VEGF-A165 and PDGF-BB with alginate hydrogels after myocardial infarction
aKarolinska Institute at Department of Internal Medicine, Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
bSchool of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA
cKarolinska Institute at Department of Thoracic Surgery, Karolinska University Hospital, Stockholm, Sweden
dKarolinska Institute at Department of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden
* Corresponding author. Department of Cardiology, Karolinska University Hospital, S-141 86 Stockholm, Sweden. Tel.: +46 8 58580000; fax: +46 8 585 86710. Christer.Sylven{at}ki.se
Objective This study investigates whether local sequential delivery of vascular endothelial growth factor-A165 (VEGF-A165) followed by platelet-derived growth factor-BB (PDGF-BB) with alginate hydrogels could induce an angiogenic effect and functional improvement greater than single factors after myocardial infarction.
Methods Alginate hydrogels were prepared by combining high and low molecular weight alginate. Growth factor release rates were monitored over time in vitro with 125I-labelled VEGF-A165 and PDGF-BB included in the gels. One week after myocardial infarction was induced in Fisher rats, gels with VEGF-A165, PDGF-BB, or both were given intra-myocardially along the border of the myocardial infarction. Vessel density was analysed in hearts and cardiac function was determined by Tissue Doppler Echocardiography. In addition, the angiogenic effect of sequenced delivery was studied in vitro in aortic rings from C57B1/6 mice.
Results Alginate gels were capable of delivering VEGF-A165 and PDGF-BB in a sustainable manner, and PDGF-BB was released more slowly than VEGF-A165. Sequential growth factor administration led to a higher density of 
-actin positive vessels than single factors, whereas no further increment was found in capillary density. Sequential protein delivery increased the systolic velocity-time integral and displayed a superior effect than single factors. In the aortic ring model, sequential delivery led to a higher angiogenic effect than single factor administration.
Conclusions The alginate hydrogel is an effective and promising injectable delivery system in a myocardial infarction model. Sequential growth factor delivery of VEGF-A165 and PDGF-BB induces mature vessels and improves cardiac function more than each factor singly. This may indicate clinical utility.
KEYWORDS Angiogenesis; Growth factors; Tissue engineering; Ventricular function; Infarction
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