Growth factor delivery from self-assembling nanofibers to facilitate islet transplantation.
Recent advances in nanotechnology and molecular self-assembly may provide novel solutions to current cell transplantation deficiencies. Heparin-binding peptide amphiphiles (HBPAs) self-assemble from aqueous media into nanofibers that bind growth factors through interactions with the bioactive polymer heparin. In this report, we demonstrate that delivery of vascular endothelial growth factor and fibroblast growth factor-2 from HBPA scaffolds significantly increases blood vessel density in the mouse omentum over control scaffolds without growth factors (P<0.0005) and significantly enhances islet engraftment. Diabetic recipients transplanted with 250 isologous islets and HBPA scaffolds containing vascular endothelial growth factor/fibroblast growth factor-2 achieved normoglycemia at a higher rate (78%) than control animals receiving identical scaffolds without growth factors (30%; P<0.05) or growth factors alone (20%). These data indicate that the enhanced engraftment can be attributed to specific growth factor effects that were made possible by the delivery mechanism of HBPA nanostructures.
Stendahl
John C
JC
Institute for BioNanotechnology in Medicine, Northwestern University, Chicago, IL, USA.
Wang
Ling-Jia
LJ
Chow
Lesley W
LW
Kaufman
Dixon B
DB
Stupp
Samuel I
SI
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology*; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D049329:Nanostructures; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009852:Omentum / Q000098:blood supply / Q000601:surgery; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
D001786:Blood Glucose; D010455:Peptides; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D016222:Fibroblast Growth Factor 2; D006493:Heparin; D040301:Vascular Endothelial Growth Factor Receptor-2