Dual Aptamer-Functionalized in Situ Injectable Fibrin Hydrogel for Promotion of Angiogenesis via Codelivery of Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor-BB

ACS Appl Mater Interfaces. 2019 May 22;11(20):18123-18132. doi: 10.1021/acsami.9b02462. Epub 2019 May 7.

Abstract

In situ injectable hydrogels hold great potential for in vivo applications such as drug delivery and regenerative medicine. However, it is challenging to ensure stable sequestration and sustained release of loaded biomolecules in these hydrogels. As aptamers have high binding affinities and specificities against target biomolecules, we studied the capability of aptamers in functionalizing in situ injectable fibrin (Fn) hydrogels for in vivo delivery of two growth factors including vascular endothelial growth factor (VEGF) and platelet-derived growth factor-BB (PDGF-BB). The results show that aptamer-functionalized fibrinogen (Fg) could form in situ injectable Fn hydrogels with porous structures. The aptamer-functionalized Fn hydrogels could sequester more VEGF and PDGF-BB than the native Fn and release these growth factors in a sustained manner with high bioactivity. After the aptamer-functionalized Fn hydrogels were subcutaneously injected into mice, the codelivery of VEGF and PDGF-BB could promote the growth of mature blood vessels. Therefore, this study has successfully demonstrated that aptamer-functionalized in situ injectable hydrogels hold great potential for in vivo codelivery of multiple growth factors and promotion of angiogenesis .

Keywords: angiogenesis; aptamer; drug delivery; growth factor; hydrogel.

MeSH terms

  • Animals
  • Aptamers, Nucleotide* / chemistry
  • Aptamers, Nucleotide* / pharmacology
  • Becaplermin* / chemistry
  • Becaplermin* / pharmacology
  • Female
  • Fibrin* / chemistry
  • Fibrin* / pharmacology
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Neovascularization, Physiologic / drug effects*
  • Vascular Endothelial Growth Factor A* / chemistry
  • Vascular Endothelial Growth Factor A* / pharmacology

Substances

  • Aptamers, Nucleotide
  • Hydrogels
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Becaplermin
  • Fibrin