Self-assembling nanostructures to deliver angiogenic factors to pancreatic islets

Biomaterials. 2010 Aug;31(24):6154-61. doi: 10.1016/j.biomaterials.2010.04.002.


Supramolecular self-assembly of nanoscale filaments offers a vehicle to signal cells within dense cell aggregates such as pancreatic islets. We previously developed a heparin-binding peptide amphiphile (HBPA) that self-assembles into nanofiber gels at concentrations of 1% by weight when mixed with heparin and activates heparin-binding, angiogenic growth factors. We report here on the use of these molecules at concentrations 100 times lower to drive delivery of the nanofibers into the dense islet interior. Using fluorescent markers, HBPA molecules, heparin, and FGF2 were shown to be present in and on the surface of murine islets. The intraislet nanofibers were found to be necessary to retain FGF2 within the islet for 48 h and to increase cell viability significantly for at least 7 days in culture. Furthermore, enhanced insulin secretion was observed with the nanofibers for 3 days in culture. Delivery of FGF2 and VEGF in conjunction with the HBPA/heparin nanofibers also induced a significant amount of islet endothelial cell sprouting from the islets into a peptide amphiphile 3-D matrix. We believe the infiltration of bioactive nanofibers in the interior of islets as an artificial ECM can improve cell viability and function in vitro and enhance their vascularization in the presence of growth factors such as FGF2 and VEGF. The approach described here may have significant impact on islet transplantation to treat type 1 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / administration & dosage*
  • Animals
  • Biological Assay
  • Cell Survival / drug effects
  • Drug Delivery Systems / methods*
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Glucose / pharmacology
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / blood supply
  • Islets of Langerhans / cytology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Male
  • Mice
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Nanostructures / chemistry*
  • Neovascularization, Physiologic / drug effects


  • Angiogenesis Inducing Agents
  • Insulin
  • Glucose