Proceedings of the National Academy of Sciences · 2006 · 613 citations · 20 references
EngineeringBioengineeringBiotechnologyBiomaterialsDrug DeliveryTissue EngineeringBiomaterials For Tissue EngineeringCardiac RegenerationCardiac Tissue EngineeringGrowth Factor DeliveryPeptide DeliveryProtein DeliveryCardiac Cell EngraftmentCardiomyocyte DifferentiationInsulin-like Growth Factor-1Myocardial Infarction RepairMyocardial RepairMyocardial Tissue EngineeringNanofibersSelf-assembling Biomaterials
Cell injection strategies for cardiac repair are limited by poor engraftment, survival, and differentiation. The authors designed biotinylated peptide nanofibers to deliver IGF‑1 locally and sustain its release, aiming to improve cardiac function after myocardial injury. IGF‑1 was conjugated to streptavidin and bound to biotinylated self‑assembling peptides, forming nanofibers that retained IGF‑1 while still assembling within the myocardium. In rats, the nanofiber‑mediated IGF‑1 delivery activated Akt, reduced caspase‑3 cleavage, increased troponin I and myocyte size, and ultimately improved systolic function after infarction.
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.
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Control of protein–ligand recognition using a stimuli-responsive polymer
Patrick S. Stayton, Tsuyoshi Shimoboji, Cynthia J. Long et al. · Nature · 1995 · 677 citations