Controlled Co-delivery of Growth Factors through Layer-by-Layer Assembly of Core-Shell Nanofibers for Improving Bone Regeneration

ACS Nano. 2019 Jun 25;13(6):6372-6382. doi: 10.1021/acsnano.8b06032. Epub 2019 Jun 13.


The regeneration of bone tissue is regulated by both osteogenic and angiogenic growth factors which are expressed in a coordinated cascade of events. The aim of this study was to create a dual growth factor-release system that allows for time-controlled release to facilitate bone regeneration. We fabricated core-shell SF/PCL/PVA nanofibrous mats using coaxial electrospinning and layer-by-layer (LBL) techniques, where bone morphogenetic protein 2 (BMP2) was incorporated into the core of the nanofibers and connective tissue growth factor (CTGF) was attached onto the surface. Our study confirmed the sustained release of BMP2 and a rapid release of CTGF. Both in vitro and in vivo experiments demonstrated improvements in bone tissue recovery with the dual-drug release system. In vivo studies showed improvement in bone regeneration by 43% compared with single BMP2 release systems. Time-controlled release enabled by the core-shell nanofiber assembly provides a promising strategy to facilitate bone healing.

Keywords: bone defects; coaxial electrospinning; controlled release; growth factor; layer-by-layer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / chemistry*
  • Bone Regeneration*
  • Cells, Cultured
  • Connective Tissue Growth Factor / chemistry*
  • Drug Liberation*
  • Mesenchymal Stem Cell Transplantation / methods
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Nanofibers / chemistry*
  • Polyesters / chemistry
  • Polyvinyl Alcohol / chemistry


  • Bone Morphogenetic Protein 2
  • Polyesters
  • Connective Tissue Growth Factor
  • polycaprolactone
  • Polyvinyl Alcohol