Enhanced angiogenesis in porous collagen-chitosan scaffolds loaded with angiogenin

Tissue Eng Part A. 2008 Nov;14(11):1775-85. doi: 10.1089/ten.tea.2007.0007.

Abstract

Artificial dermis lacks a vascular network, and angiogenesis is slow in vivo. Controlled delivery of angiogenin (ANG), a potent inducer of angiogenesis, should promote angiogenesis in artificial dermis. In this study, a porous collagen-chitosan scaffold was fabricated and heparinized using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS) with a freeze-drying method. Using radioiodine labeling, the effect of heparin on the binding of ANG to the scaffold was studied. The release of ANG from the heparinized scaffold was investigated using a radioiodine labeling method or an enzyme-linked immunosorbent assay method. In vivo angiogenesis of the scaffold was studied for 28 days. All scaffolds possess three-dimensional porous structures, and their mean pore sizes increase upon EDC-NHS cross-linking. The binding of ANG to the scaffold showed a linear correlation with ANG concentration. With ANG concentrations of 160 ng/mL, the binding of ANG to the heparinized scaffold was 36.5%. In vitro, ANG was released from the heparinized scaffold in a controlled manner. The presence of ANG enhanced the angiogenesis of the heparinized scaffold after subcutaneous implantation into rabbits. The results of this study indicate that a porous collagen-chitosan scaffold loaded with ANG may be valuable in the development of artificial dermis requiring enhanced angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chitosan / chemistry*
  • Chitosan / metabolism
  • Collagen / chemistry*
  • Collagen / metabolism
  • Humans
  • Microscopy, Electron, Scanning
  • Neovascularization, Physiologic / drug effects
  • Porosity
  • Protein Binding
  • Rabbits
  • Ribonuclease, Pancreatic / chemistry*
  • Ribonuclease, Pancreatic / metabolism
  • Ribonuclease, Pancreatic / pharmacology
  • Skin, Artificial
  • Tissue Engineering / methods*
  • Tissue Scaffolds / chemistry*

Substances

  • Collagen
  • Chitosan
  • angiogenin
  • Ribonuclease, Pancreatic