Controlled dual delivery of BMP-2 and dexamethasone by nanoparticle-embedded electrospun nanofibers for the efficient repair of critical-sized rat calvarial defect

Biomaterials. 2015 Jan:37:218-29. doi: 10.1016/j.biomaterials.2014.10.015. Epub 2014 Oct 23.

Abstract

There is an urgent need to develop biomimetic bone tissue engineering scaffolds for the repair of critical-sized calvarial defect. In this study, we developed a new nanoparticle-embedded electrospun nanofiber scaffold for the controlled dual delivery of BMP-2 and dexamethasone (DEX). The scaffold was achieved by (1) the encapsulation of BMP-2 into bovine serum albumin (BSA) nanoparticles to maintain the bioactivity of BMP-2 and (2) the co-electrospinning of the blending solution composed of the BSA nanoparticles, DEX and the poly(ε-caprolactone)-co-poly(ethylene glycol) (PCE) copolymer. The in vitro studies showed that the bioactivity of DEX and BMP-2 was preserved in the dual-drug-loaded nanofiber scaffold, and a sequential release pattern in which most of the DEX was released in the original eight days and the BMP-2 release lasted up to 35 days was achieved. The in vitro osteogenesis study demonstrated that the drug-loaded groups exhibited a strong ability to induce differentiation toward osteoblasts. In vivo osteogenesis studies also revealed that the degrees of repair of rat calvarial defect achieved with the drug-loaded nanofiber scaffolds were significantly better than those obtained with the blank materials; in particular, the dual-drug-loaded nanofiber scaffold manifested the best repair efficacy due to a synergistic effect of BMP-2 and DEX. Therefore, the dual-drug-loaded nanofiber scaffold is deemed a strong potential candidate for the repair of bone defects in bone tissue engineering.

Keywords: Critical bone defect; Drug delivery; Electrospinning; Nanofiber; Nanoparticle; Tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone Morphogenetic Protein 2 / administration & dosage*
  • Bone Morphogenetic Protein 2 / pharmacology
  • Cattle
  • Delayed-Action Preparations
  • Dexamethasone / administration & dosage*
  • Dexamethasone / pharmacology
  • Female
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / enzymology
  • Nanofibers / chemistry*
  • Nanofibers / ultrastructure
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Osteogenesis / drug effects
  • Rats, Sprague-Dawley
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacology
  • Skull / drug effects*
  • Skull / pathology*
  • Staining and Labeling
  • Tissue Engineering / methods*
  • Tissue Scaffolds / chemistry
  • Transforming Growth Factor beta / administration & dosage*
  • Transforming Growth Factor beta / pharmacology
  • Wound Healing / drug effects*

Substances

  • Bone Morphogenetic Protein 2
  • Delayed-Action Preparations
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2
  • Dexamethasone
  • Alkaline Phosphatase