Self-assembling nanostructures to deliver angiogenic factors to pancreatic islets

Lesley W. Chow, Ling jia Wang, Dixon B. Kaufman, Samuel I Stupp

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)6154-6161
Number of pages8
JournalBiomaterials
Volume31
Issue number24
DOIs
Publication statusPublished - Aug 2010

Fingerprint

Nanostructures
Nanofibers
Angiogenesis Inducing Agents
Islets of Langerhans
Heparin
Amphiphiles
Fibroblast Growth Factor 2
Peptides
Vascular Endothelial Growth Factor A
Cell Survival
Intercellular Signaling Peptides and Proteins
Cells
Military electronic countermeasures
Islets of Langerhans Transplantation
Molecules
Insulin
Endothelial cells
Medical problems
Type 1 Diabetes Mellitus
Infiltration

Keywords

  • Angiogenesis
  • Cell viability
  • Diabetes
  • Heparin
  • Peptide
  • Self-assembly

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics
  • Medicine(all)

Cite this

Self-assembling nanostructures to deliver angiogenic factors to pancreatic islets. / Chow, Lesley W.; Wang, Ling jia; Kaufman, Dixon B.; Stupp, Samuel I.

In: Biomaterials, Vol. 31, No. 24, 08.2010, p. 6154-6161.

Research output: Contribution to journalArticle

Chow, Lesley W. ; Wang, Ling jia ; Kaufman, Dixon B. ; Stupp, Samuel I. / Self-assembling nanostructures to deliver angiogenic factors to pancreatic islets. In: Biomaterials. 2010 ; Vol. 31, No. 24. pp. 6154-6161.
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