Anti-VEGF-R2 Aptamer and RGD Peptide Synergize in a Bifunctional Hydrogel for Enhanced Angiogenic Potential

Hydrogels have gained interest for use in tissue regeneration and wound healing because of their absorbing and swelling properties as well as their ability to mimic the natural extracellular matrix. Their use in wound healing specifically may be in the form of a patch or wound dressing or they may be administered within the wound bed as a filler, gel in situ, to promote healing. Thiolated hyaluronic acid-polyethylene diacrylate (tHA-PEGDA) hydrogels are ideal for this purpose due to their short gelation times at physiological temperature and pH. But these hydrogels alone are not enough and require added components to gain bioactivity. In this work, RGD adhesion peptides and an antivascular endothelial growth factor receptor-2 (VEGF-R2) DNA aptamer are incorporated into a tHA-PEGDA hydrogel to make a bifunctional hyaluronic acid hydrogel. RGD peptides promote attachment and growth of cells while the anti-VEGF-R2 DNA aptamer seems to improve cell viability, induce cell migration, and spur the onset of angiogenesis by tube formation by endothelial cells. This bifunctional hydrogel supports cell culture and has improved biological properties. The data suggest that these hydrogels can be used for advanced tissue regeneration applications such as in wound healing.