Osteogenic/angiogenic dual growth factor delivery microcapsules for regeneration of vascularized bone tissue

Adv Healthc Mater. 2015 Sep 16;4(13):1982-92. doi: 10.1002/adhm.201500341. Epub 2015 Jul 2.


Growth factors (GFs) are major biochemical cues for tissue regeneration. Herein, a novel dual GF delivery system is designed composed of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and alginate microcapsules (MCs) via an electrodropping method. While bone morphogenetic protein (BMP)-2 is encapsulated in the PLGA NPs, vascular endothelial growth factor (VEGF) is included in the alginate MCs, where BMP-2-loaded PLGA NPs are entrapped together in the fabrication process. The initial loading efficiencies of BMP-2 and VEGF are 78% ± 3.6% and 43% ± 1.7%, respectively. When our dual GF-loaded MCs are assessed for in vitro osteogenesis of umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) on 2D and 3D environment, MCs contribute to much better UCB-MSCs osteogenesis as confirmed by von Kossa staining, immunofluorescence (osteocalcin, collagen 1), calcium content measurement, and osteogenic markers expression. In addition, when dual GF-encapsulated MCs are combined with collagen and then applied to 8 mm diameter rat calvarial defect model, the positive effects on vascularized bone regeneration are much more pronounced; micro computed tomography (CT) and histology analyses exhibit 82.3% bone healing coupled with 12.6% vessel occupied area. Put together, current study indicates a synergistic effect of BMP-2/VEGF and highlights the great potential of dual GF delivery modality (PLGA NPs-in-MC) for regeneration of vascularized bone.

Keywords: bone regeneration; dual growth factor delivery; microcapsules; nanoparticles; umbilical cord, mesenchymal stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / chemistry
  • Animals
  • Bone Diseases / therapy
  • Bone Morphogenetic Protein 2 / chemistry
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Bone Regeneration / drug effects*
  • Capsules / chemistry*
  • Drug Carriers / chemistry*
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / chemistry
  • Lactic Acid / chemistry
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Nanoparticles / chemistry
  • Osteogenesis / drug effects
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats
  • Rats, Sprague-Dawley
  • Umbilical Cord / cytology
  • Vascular Endothelial Growth Factor A / chemistry
  • Vascular Endothelial Growth Factor A / pharmacology*
  • X-Ray Microtomography


  • Alginates
  • Bone Morphogenetic Protein 2
  • Capsules
  • Drug Carriers
  • Hexuronic Acids
  • Vascular Endothelial Growth Factor A
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Glucuronic Acid