Self-assembled VEGF-R2 targeting DNA aptamer-collagen fibers stimulate an angiogenic-like endothelial cell phenotype

Vascularization of engineered tissue is one of the hallmark challenges of tissue engineering. Leveraging self-assembled nucleic acid-collagen complexes (NACCs), we mixed a VEGF-R2 targeting aptamer or its receptor agonist divalent assembly with type I collagen to assemble NACC microfibers. Human umbilical vein endothelial cells (HUVECs) quickly remodeled these fibers into tubulogenic-like structures over 48 h. Moreover, NACCs made with the receptor agonist divalent aptamer assembly promoted enhanced expression of von Willebrand factor (vWF), angiopoietin-2 (ANGPT-2), and matrix metalloproteinase-2 (MMP-2) by HUVECs as measured by either immunocytochemistry or ELISA. The findings suggest, endothelial cell phenotype was directed by both biochemical cues afforded by the agonist behavior of the divalent aptamer assembly as well as by the biophysical cues afforded by the fibrous topography. Collectively, these results support the development of an angiogenic endothelial cell phenotype stimulated by the VEGF-R2 agonist NACC fibers. Thus, the combination of engineered DNA aptamer nanotechnology and DNA-collagen complexation phenomena is a promising biofunctional natural scaffold material system for tissue engineering and regenerative medicine applications.