Sustained release of platelet-derived growth factor and vascular endothelial growth factor from silk/calcium phosphate/PLGA based nanocomposite scaffold

Int J Pharm. 2013 Sep 15;454(1):216-25. doi: 10.1016/j.ijpharm.2013.06.080. Epub 2013 Jul 12.

Abstract

To exploit the therapeutic potential of growth factors in tissue regeneration, it is necessary to design a porous scaffold in order to concurrently accommodate cells and release angiogenic factors in a controlled manner. In an attempt to address these issues, we developed a nanocomposite scaffold based on silk/calcium phosphate/PLGA by freeze-drying and electrospinning in order to control the release of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). The highly porous scaffold possessed appropriate chemical and physical structure as confirmed by FTIR, XRD, SEM, and Zeta potential analysis. Furthermore, the incorporation of PDGF and VEGF in the scaffold was confirmed using Raman spectroscopy while their bioactivity was maintained by 82% and 89% for up to 28 days, respectively. The release of PDGF was slower than VEGF as respected. Additionally, the scaffold could promote proliferation, alkaline phosphatase production and attachment of human osteoblast cells. Histological examination established new bone matrix formation with neovascularization in the angiogenic factors loaded scaffold after 10 weeks of implantation in rabbit model. Finally, it was considered that the fabricated nanocomposite could be useful for bone tissue engineering applications.

Keywords: Bone tissue engineering; Controlled release; PDGF; Silk/calcium phosphate/PLGA; VEGF.

MeSH terms

  • Animals
  • Calcium Phosphates / chemistry*
  • Cells, Cultured
  • Chemistry, Pharmaceutical
  • Delayed-Action Preparations
  • Drug Carriers*
  • Freeze Drying
  • Humans
  • Lactic Acid / chemistry*
  • Microscopy, Electron, Scanning
  • Nanocomposites*
  • Neovascularization, Physiologic / drug effects
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteogenesis / drug effects
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Porosity
  • Powder Diffraction
  • Proto-Oncogene Proteins c-sis / chemistry
  • Proto-Oncogene Proteins c-sis / metabolism*
  • Proto-Oncogene Proteins c-sis / pharmacology
  • Rabbits
  • Silk / chemistry*
  • Solubility
  • Spectroscopy, Fourier Transform Infrared
  • Spectrum Analysis, Raman
  • Technology, Pharmaceutical / methods
  • Time Factors
  • Tissue Engineering / methods
  • Tissue Scaffolds*
  • Vascular Endothelial Growth Factor A / chemistry
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vascular Endothelial Growth Factor A / pharmacology
  • X-Ray Diffraction

Substances

  • Calcium Phosphates
  • Delayed-Action Preparations
  • Drug Carriers
  • Proto-Oncogene Proteins c-sis
  • Silk
  • Vascular Endothelial Growth Factor A
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • calcium phosphate