Abstract 17103: VEGF-Mimicking Nanostructures for Ischemic Tissue Repair
Purpose: Repair of ischemic tissue remains an unsolved goal. Current strategies aim to enhance perfusion and, thereby, overcome dysfunction of ischemic tissue. Neovascularization can be achieved via pro-angiogenic agents that enhance sprouting from preexisting vessels (angiogenesis). Due to practical limitations, therapeutic angiogenesis has not shown convincing results in patients. Advances in bionanotechnology, however, enable the development of specific biomaterials to therapeutically improve recovery.
Methods/Results: We chose the self-assembling peptide amphiphile (PA) nanofiber platform to design a pro-angiogenic nanofiber that mimics the activity of a pro-angiogenic factor VEGF (VEGF-PA) to enhance angiogenesis. Incubation of human umbilical vein endothelial cells (HUVECs) with VEGF-PA induced cellular functions important for angiogenesis: Compared to untreated control cells, HUVECs treated with VEGF-PA were more resistant to serum-starvation (Annexin staining: VEGF-PA 10±3%, control 32±3, n=6, P<0.001), more mitogenic (CyQuant proliferation assay: VEGF-PA 137±2%, control 100±1%, n=8, P<0.001), and migrated better (scratch assay, reduction of denuded area: VEGF-PA 69±4, control 25±13%, n=6, P<0.05). In a chicken embryo angiogenesis assay, VEGF-PA showed a substantial pro-angiogenic activity (VEGF-PA 229±19%, saline 132±5%, n=16, P<0.001). Local injection of VEGF-PA enhanced limb recovery after surgical hind-limb ischemia in 8-week-old, male FVB/N mice. At day 28, VEGF-PA treated animals showed better perfusion (laser Doppler, ischemic/non-ischemic limb ratio: VEGF-PA 0.7±0.1, saline 0.5±0.1, P<0.05), less tissue damage (score: VEGF-PA 4.2±0.2, saline 3.5±0.2, P<0.05), and better motor function (score: VEGF-PA 4.2±0.2, saline 3.4±0.2, P<0.01) of the ischemic limb. Better recovery after VEGF-PA treatment is associated with more CD31+ capillaries in the ischemic muscle (VEGF-PA 1582±76/mm2, saline 93±53/mm2, P<0.001).
Conclusion: Self-assembling, pro-angiogenic PA nanofibers mimicking VEGF enhance ischemic tissue repair and thereby constitute a novel therapeutic alternate to overcome practical limitations in therapeutic angiogenesis.
- © 2011 by American Heart Association, Inc.