Sequential BMP-2/BMP-7 delivery from polyester nanocapsules

J Biomed Mater Res A. 2010 May;93(2):528-36. doi: 10.1002/jbm.a.32520.


The aim of this study was to develop a nanosized, controlled growth factor release system to incorporate into tissue engineering scaffolds and thus activate the cells seeded in the scaffold. Nanocapsules of poly(lactic acid-co-glycolic acid) (PLGA) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) were loaded with the bone morphogenetic proteins BMP-2 and BMP-7, respectively, and with bovine serum albumin (BSA), the model protein. BSA-loading efficiency and release kinetics were used to determine the most appropriate nanocapsule pair to achieve the delivery of growth factors in a sequential manner, as occurs in natural processes. BSA-encapsulation efficiency was highest when the polymer concentration used in the preparation of PLGA and PHBV nanocapsules was 10% (w/v) (84.75% and 16.72%, respectively). Release of BSA was faster from PLGA than it was from PHBV. Based on the encapsulation efficiency and release data, 10% PLGA and 10% PHBV nanocapsules were chosen to provide the early BMP-2 and later BMP-7 release, respectively. Simultaneous, sequential delivery and individual release of the BMPs were studied for 7, 14, and 21 days, using rat bone marrow mesenchymal stem cells. Individual BMP-2 release suppressed cell proliferation while providing higher alkaline phosphatase activity with respect to BMP-7. The sequential delivery of BMP-2 and BMP-7 provided slightly lower proliferation than did simultaneous delivery, but the highest alkaline phosphatase activity of all indicated a synergistic effect on the osteogenic differentiation of mesenchymal stem cells caused by the use of the two growth factors in a sequential fashion.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Morphogenetic Protein 2 / metabolism*
  • Bone Morphogenetic Protein 2 / pharmacology
  • Bone Morphogenetic Protein 7 / metabolism*
  • Bone Morphogenetic Protein 7 / pharmacology
  • Cattle
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Drug Delivery Systems / instrumentation
  • Drug Delivery Systems / methods*
  • Lactic Acid / chemistry
  • Male
  • Materials Testing
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Microscopy, Electron, Scanning
  • Nanocapsules / chemistry*
  • Particle Size
  • Polyesters / chemistry*
  • Polyesters / metabolism
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats
  • Rats, Sprague-Dawley
  • Serum Albumin, Bovine / metabolism
  • Tissue Engineering / instrumentation
  • Tissue Engineering / methods


  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 7
  • Nanocapsules
  • Polyesters
  • poly(3-hydroxybutyrate)-co-(3-hydroxyvalerate)
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Serum Albumin, Bovine
  • Lactic Acid