Dynamic in vivo biocompatibility of angiogenic peptide amphiphile nanofibers

Shahram Ghanaati, Matthew J. Webber, Ronald E. Unger, Carina Orth, James F. Hulvat, Sarah E. Kiehna, Mike Barbeck, Angela Rasic, Samuel I. Stupp, C. James Kirkpatrick

Research output: Contribution to journalArticlepeer-review

110 Scopus citations


Biomaterials that promote angiogenesis have great potential in regenerative medicine for rapid revascularization of damaged tissue, survival of transplanted cells, and healing of chronic wounds. Supramolecular nanofibers formed by self-assembly of a heparin-binding peptide amphiphile and heparan sulfate-like glycosaminoglycans were evaluated here using a dorsal skinfold chamber model to dynamically monitor the interaction between the nanofiber gel and the microcirculation, representing a novel application of this model. We paired this model with a conventional subcutaneous implantation model for static histological assessment of the interactions between the gel and host tissue. In the static analysis, the heparan sulfate-containing nanofiber gels were found to persist in the tissue for up to 30 days and revealed excellent biocompatibility. Strikingly, as the nanofiber gel biodegraded, we observed the formation of a de novo vascularized connective tissue. In the dynamic experiments using the dorsal skinfold chamber, the material again demonstrated good biocompatibility, with minimal dilation of the microcirculation and only a few adherent leukocytes, monitored through intravital fluorescence microscopy. The new application of the dorsal skinfold model corroborated our findings from the traditional static histology, demonstrating the potential use of this technique to dynamically evaluate the biocompatibility of materials. The observed biocompatibility and development of new vascularized tissue using both techniques demonstrates the potential of these angiogenesis-promoting materials for a host of regenerative strategies.

Original languageEnglish
Pages (from-to)6202-6212
Number of pages11
Issue number31
StatePublished - Oct 2009
Externally publishedYes

Bibliographical note

Funding Information:
This work was financially supported by grants from the European Commission EXPERTISSUES Contract: (500283-2) and the USA National Institutes of Health (NIBIB) award 1RO1-EB003806-04 to S.I. Stupp. M.J. Webber was supported by the Northwestern Regenerative Medicine Training Program (RMTP) NIH award 5T90-DA022881. The authors would like to thank U. Hilbig and J. Hilbig for their excellent technical assistance. Two of the authors (J.F. Hulvat and S.E. Kiehna) are employees of Nanotope Inc., a company with a financial interest in the peptide compound used in this study. Nanotope Inc. provided the peptide compound used for these studies. There are no conflicts of interest reported by the other authors.


  • Angiogenesis
  • Biocompatibility
  • Peptide amphiphile
  • Regenerative medicine
  • Self-assembly


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