Browsing by Subject "Neovascularization"

Now showing 1 - 3 of 3

Open Access
Affinity of glycopeptide nanofibers to growth factors and their effects on cells
(2017-09) Haştar, Nurcan
The development of scaffolds for growth factor delivery is a promising approach for tissue regeneration applications due to their crucial roles during regeneration. Growth factor secretion and interactions with glycosaminoglycans are essential steps for the regulation of cellular behavior. Therefore, glycosaminoglycan-mimetic scaffolds provide a great opportunity to modulate the effects of growth factor actions on cell fate. In this thesis, sugar-bearing peptide amphiphile molecules were characterized and tested for VEGF, FGF-2 and NGF affinity. ELISA-based affinity analyses revealed that glycopeptide nanofibers had high affinity to NGF; however, glycopeptides alone were not enough to interact efficiently with VEGF and FGF-2. Since VEGF and NGF contain heparin-binding domains, the addition of a sulfonated peptide amphiphile increased the affinity of the nanofiber network to these growth factors. Glycopeptide-sulfonate nanofibers were also found to promote in vitro tube formation through their VEGF and FGF-2 affinity. VEGF release profiles of HUVECs indicated that increasing concentration of VEGF may provide autocrine signaling and enhance tube formation without any exogenous pro-angiogenic factor addition. In addition, when NGF-responsive PC-12 cells were cultured on glycopeptide nanofibers, they extended their neurites to an extent comparable with a widely-used positive control molecule (poly-L-lysine). These results suggest that glycosaminoglycan-mimetic glycopeptide nanofiber networks can be used as efficient growth factor presentation platforms for tissue regeneration applications to induce angiogenesis or peripheral nerve regeneration.
Open Access
Angiogenic peptide nanofibers repair cardiac tissue defect after myocardial infarction
(Acta Materialia Inc, 2017) Rufaihah, A. J.; Yasa, I. C.; Ramanujam, V. S.; Arularasu, S. C.; Kofidis, T.; Güler, Mustafa O.; Tekinay, A. B.
Myocardial infarction remains one of the top leading causes of death in the world and the damage sustained in the heart eventually develops into heart failure. Limited conventional treatment options due to the inability of the myocardium to regenerate after injury and shortage of organ donors require the development of alternative therapies to repair the damaged myocardium. Current efforts in repairing damage after myocardial infarction concentrates on using biologically derived molecules such as growth factors or stem cells, which carry risks of serious side effects including the formation of teratomas. Here, we demonstrate that synthetic glycosaminoglycan (GAG) mimetic peptide nanofiber scaffolds induce neovascularization in cardiovascular tissue after myocardial infarction, without the addition of any biologically derived factors or stem cells. When the GAG mimetic nanofiber gels were injected in the infarct site of rodent myocardial infarct model, increased VEGF-A expression and recruitment of vascular cells was observed. This was accompanied with significant degree of neovascularization and better cardiac performance when compared to the control saline group. The results demonstrate the potential of future clinical applications of these bioactive peptide nanofibers as a promising strategy for cardiovascular repair. Statement of Significance We present a synthetic bioactive peptide nanofiber system can enhance cardiac function and enhance cardiovascular regeneration after myocardial infarction (MI) without the addition of growth factors, stem cells or other biologically derived molecules. Current state of the art in cardiac repair after MI utilize at least one of the above mentioned biologically derived molecules, thus our approach is ground-breaking for cardiovascular therapy after MI. In this work, we showed that synthetic glycosaminoglycan (GAG) mimetic peptide nanofiber scaffolds induce neovascularization and cardiomyocyte differentiation for the regeneration of cardiovascular tissue after myocardial infarction in a rat infarct model. When the peptide nanofiber gels were injected in infarct site at rodent myocardial infarct model, recruitment of vascular cells was observed, neovascularization was significantly induced and cardiac performance was improved. These results demonstrate the potential of future clinical applications of these bioactive peptide nanofibers as a promising strategy for cardiovascular repair.
Open Access
HER2 and proliferation of wound-induced breast carcinoma
(The Lancet Publishing, 2003-11-01) Tez, M.; Göçmen, E.; Özçelik, T.