Magnetic field-responsive release of transforming growth factor beta 1 from heparin-modified alginate ferrogels

Carbohydr Polym. 2016 Oct 20:151:467-473. doi: 10.1016/j.carbpol.2016.05.090. Epub 2016 May 26.

Abstract

Stimuli-responsive polymeric systems have been widely used for various drug delivery and tissue engineering applications. Magnetic stimulation can be also exploited to regulate the release of pharmaceutical drugs, growth factors, and cells from hydrogels in a controlled manner, on-demand. In the present study, alginate ferrogels containing iron oxide nanoparticles were fabricated via ionic cross-linking, and their various characteristics were investigated. The deformation of the ferrogels was dependent on the polymer concentration, calcium concentration, iron oxide concentration, and strength of magnetic field. To modulate the release of transforming growth factor beta 1 (TGF-β1) under magnetic stimulation, alginate was chemically modified with heparin, as TGF-β1 has a heparin-binding domain. Alginate was first modified with ethylenediamine, and heparin was then conjugated to the ethylenediamine-modified alginate via carbodiimide chemistry. Conjugation of heparin to alginate was confirmed by infrared spectroscopy and proton nuclear magnetic resonance spectroscopy. Sustained release of TGF-β1 from alginate-g-heparin ferrogels was achieved, and application of a magnetic field to the ferrogels regulated TGF-β1 release, resultantly enhancing chondrogenic differentiation of ATDC5 cells, which were used as a model chondrogenic cell line. Alginate-based ferrogels that release drugs in a controlled manner may therefore be useful in many biomedical applications.

Keywords: Alginate; Ferrogel; Heparin; Magnetic field; Transforming growth factor beta 1.

MeSH terms

  • Alginates / administration & dosage
  • Alginates / chemistry
  • Animals
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Chondrogenesis / drug effects
  • Drug Delivery Systems*
  • Drug Liberation
  • Glucuronic Acid / administration & dosage
  • Glucuronic Acid / chemistry
  • Heparin / administration & dosage
  • Heparin / chemistry
  • Hexuronic Acids / administration & dosage
  • Hexuronic Acids / chemistry
  • Hydrogels / administration & dosage*
  • Hydrogels / chemistry
  • Magnetic Fields
  • Magnetic Phenomena
  • Magnetite Nanoparticles / administration & dosage
  • Magnetite Nanoparticles / chemistry
  • Mice
  • Transforming Growth Factor beta1 / administration & dosage*
  • Transforming Growth Factor beta1 / chemistry

Substances

  • Alginates
  • Hexuronic Acids
  • Hydrogels
  • Magnetite Nanoparticles
  • Transforming Growth Factor beta1
  • Glucuronic Acid
  • Heparin