Heparin Functionalized Injectable Cryogel with Rapid Shape-Recovery Property for Neovascularization

Biomacromolecules. 2018 Jun 11;19(6):2257-2269. doi: 10.1021/acs.biomac.8b00331. Epub 2018 May 3.

Abstract

Cryogel based scaffolds have high porosity with interconnected macropores that may provide cell compatible microenvironment. In addition, cryogel based scaffolds can be utilized in minimally invasive surgery due to its sponge-like properties, including rapid shape recovery and injectability. Herein, we developed an injectable cryogel by conjugating heparin to gelatin as a carrier for vascular endothelial growth factor (VEGF) and fibroblasts in hindlimb ischemic disease. Our gelatin/heparin cryogel showed gelatin concentration-dependent mechanical properties, swelling ratios, interconnected porosities, and elasticities. In addition, controlled release of VEGF led to effective angiogenic responses both in vitro and in vivo. Furthermore, its sponge-like properties enabled cryogels to be applied as an injectable carrier system for in vivo cells and growth factor delivery. Our heparin functionalized injectable cryogel facilitated the angiogenic potential by facilitating neovascularization in a hindlimb ischemia model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Immobilized / metabolism
  • Cells, Immobilized / pathology
  • Cells, Immobilized / transplantation*
  • Cryogels* / chemistry
  • Cryogels* / pharmacology
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Fibroblasts / transplantation*
  • Heparin* / chemistry
  • Heparin* / pharmacology
  • Hindlimb / blood supply*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Ischemia / metabolism
  • Ischemia / pathology
  • Ischemia / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neovascularization, Physiologic / drug effects*
  • Vascular Endothelial Growth Factor A* / chemistry
  • Vascular Endothelial Growth Factor A* / pharmacology

Substances

  • Cryogels
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Heparin