Strategies for cardiac repair include injection of cells, but these approaches 
have been hampered by poor cell engraftment, survival, and differentiation. To 
address these shortcomings for the purpose of improving cardiac function after 
injury, we designed self-assembling peptide nanofibers for prolonged delivery of 
insulin-like growth factor 1 (IGF-1), a cardiomyocyte growth and differentiation 
factor, to the myocardium, using a "biotin sandwich" approach. Biotinylated 
IGF-1 was complexed with tetravalent streptavidin and then bound to biotinylated 
self-assembling peptides. This biotin sandwich strategy allowed binding of IGF-1 
but did not prevent self-assembly of the peptides into nanofibers within the 
myocardium. IGF-1 that was bound to peptide nanofibers activated Akt, decreased 
activation of caspase-3, and increased expression of cardiac troponin I in 
cardiomyocytes. After injection into rat myocardium, biotinylated nanofibers 
provided sustained IGF-1 delivery for 28 days, and targeted delivery of IGF-1 in 
vivo increased activation of Akt in the myocardium. When combined with 
transplanted cardiomyocytes, IGF-1 delivery by biotinylated nanofibers decreased 
caspase-3 cleavage by 28% and increased the myocyte cross-sectional area by 25% 
compared with cells embedded within nanofibers alone or with untethered IGF-1. 
Finally, cell therapy with IGF-1 delivery by biotinylated nanofibers improved 
systolic function after experimental myocardial infarction, demonstrating how 
engineering the local cellular microenvironment can improve cell therapy.