BMP-2 encapsulated polysaccharide nanoparticle modified biphasic calcium phosphate scaffolds for bone tissue regeneration

J Biomed Mater Res A. 2015 Apr;103(4):1520-32. doi: 10.1002/jbm.a.35282. Epub 2014 Aug 7.

Abstract

Bone morphology protein-2 (BMP-2) encapsulated chitosan/chondrotin sulfate nanoparticles (CHI/CS NPs) are developed to enhance ectopic bone formation on biphasic calcium phosphate (BCP) scaffolds. BMP-2 contained CHI/CS NPs were prepared by a simple and mild polyelectrolyte complexation process. It does not involve harsh organic solvents and high temperature, and therefore retain growth factors activity. These NPs were immobilized on BCP scaffolds, and realize the sustained release of growth factors from the scaffolds. The bare BCP scaffolds, NP loaded scaffolds (BCP-NP), and NP loaded and polydopamine coated scaffolds (BCP-Dop-NP) were seeded with bone marrow stroma cells (BMSC) to evaluate the osteoinductivity of the scaffolds. BMSC culture results indicate that all scaffolds favor cell adhesion, proliferation, differentiation. Afterwards, the bare BCP, BCP-NP, and BCP-Dop-NP scaffolds were implanted into rabbits intramuscularly to evaluate the ectopic bone formation of scaffolds. In vivo results indicate that the BCP-NP and BCP-Dop-NP scaffolds enhance more ectopic bone formation than the bare BCP scaffolds. Both the in vitro and in vivo results demonstrate that BMP-2 encapsulated polysaccharide NPs are effective to improve the osteoinductivity of the scaffolds. In addition, BCP-NP scaffolds induce more bone formation than BCP-Dop-NP scaffolds. This is because BCP-NP scaffolds harness the intrinsic osteoinductivity BCP and BMP-2, whereas BCP-Dop-NP scaffolds have polydopamine coatings that inhibit the surfaces biological features of BCP scaffolds, and therefore weaken the bone formation ability of scaffolds.

Keywords: BMP-2; biphasic calcium phosphate scaffolds; bone tissue regeneration; chitosan; chondroitin sulfate; nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Bone Regeneration / drug effects*
  • Cattle
  • Cell Adhesion / drug effects
  • Chitosan / pharmacology
  • Chondroitin Sulfates / pharmacology
  • Collagen Type I / metabolism
  • Hydroxyapatites / pharmacology*
  • Immunohistochemistry
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Osteogenesis / drug effects
  • Particle Size
  • Polysaccharides / pharmacology*
  • Rabbits
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology
  • Serum Albumin, Bovine / metabolism
  • Staining and Labeling
  • Static Electricity
  • Tissue Scaffolds / chemistry*
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Bone Morphogenetic Protein 2
  • Collagen Type I
  • Hydroxyapatites
  • Polysaccharides
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • hydroxyapatite-beta tricalcium phosphate
  • recombinant human bone morphogenetic protein-2
  • Serum Albumin, Bovine
  • Chondroitin Sulfates
  • Chitosan