Abstract 520: Promoting Angiogenesis with Heparin-Binding Nanostructures
Background Controlling angiogenesis is of interest in regenerative medicine, wound healing, and cancer treatments. We report here the use of heparin to nucleate nanostructures that can display these macromolecules on their surfaces in order to more effectively bind and activate angiogenic growth factors for cell signaling. We also examine the potential of nanoscale fibers to promote vascularization and improve the recovery after the ischemia attack in the hear and skin.
Methods and Results Heparin, a biopolymer known to bind to angiogenic growth factor domains, was used to nucleate self-assembly of nanoscale fibers from designed peptide amphiphile molecules. This process yielded rigid scaffolds presenting on their surface heparin chains that can capture or display growth factors for cell signaling. For the in vitro angiogenesis assay, bovine pulmonary artery endothelial cells were cultured between the nanofiber heparin gels with growth factors and showed branched anastomosing networks organized tubular structures with continuous lumina penetrating through the thickness of the gel. The structures resembled capillary networks with a high degree of organization. The in vivo rat cornea angiogenesis assay was performed by placing nanofiber gel with VEGF and FGF-2 into a surgically created pocket in the rat cornea. This treatment showed a statistically significant increase in the neovascularization response, as determined by the ratio of the corneal area involved in the response, the average length of blood vessels, and the maximum length of blood vessels formed in each eye. Using only nanogram quantities of VEGF and FGF-2, self-assembly of the nanostructures in heart muscle restored a significant level of cardiovascular function in a chronic ischemic mouse infarct model. In ischemic rabbit ear wounds, the nanostructures promoted healing even without exogeneous growth factors.
CONCLUSIONS These experiments demonstrate that self-assembling peptides can promote vascularization and improve the recovery after the ischemia attack. Since these peptide nanofibers may be modified in a variety of ways, this approach may enable injectable tissue regeneration and recovery strategies.