Proper spatio-temporal delivery of multiple therapeutic proteins represents a 
major challenge in therapy strategies aimed at inducing myocardial regeneration 
after myocardial infarction (MI). We hypothesized that the dual delivery of 
insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) by 
injectable affinity-binding alginate biomaterial would maximize their 
therapeutic effects, leading to a more favorable course of tissue restoration 
after acute MI. A sequential release of IGF-1 followed by HGF was attained from 
affinity-binding alginate biomaterial, which also protected the proteins from 
proteolysis (shown by mass spectroscopy). The released factors retained 
bioactivity, as judged by their capability to activate their respective 
signaling pathways and to prevent cardiomyocyte apoptosis in vitro. In a rat 
model of acute MI, an intramyocardial injection of the dual IGF-1/HGF 
affinity-bound alginate biomaterial preserved scar thickness, attenuated infarct 
expansion and reduced scar fibrosis after 4 weeks, concomitantly with increased 
angiogenesis and mature blood vessel formation at the infarct. Furthermore, this 
treatment prevented cell apoptosis, induced cardiomyocyte cell cycle re-entry 
and increased the incidence of GATA-4-positive cell clusters. The dual delivery 
of IGF-1 and HGF from affinity-binding alginate biomaterial represents a useful 
strategy to treat MI. It showed a marked therapeutic efficacy at various tissue 
levels, as well as potential to induce endogenous regeneration of cardiac 
muscle.