Synchronous delivery of hydroxyapatite and connective tissue growth factor derived osteoinductive peptide enhanced osteogenesis

J Control Release. 2019 May 10:301:129-139. doi: 10.1016/j.jconrel.2019.02.037. Epub 2019 Mar 14.

Abstract

In bone tissue engineering, electrospun fibrous scaffolds can provide excellent mechanical support, extracellular matrix mimicking components, such as 3D spacial fibrous environment for cell growth and controlled release of signaling molecules for osteogenesis. Here, a facile strategy comprising the incorporation of an osteogenic inductive peptide H1, derived from the cysteine knot (CT) domain of connective tissue growth factor (CTGF), in the core of Silk Fibroin (SF) was developed for osteogenic induction, synergistically with co-delivering hydroxyapatite (HA) from the shell of poly(l-lactic acid-co-ε-caprolactone) (PLCL). The core-shell nanofibrous structure was confirmed by transmission electron microscopy (TEM). Furthermore, the sustained released H1 has effectively promoted proliferation and osteoblastic differentiation of human induced pluripotent stem cells-derived mesenchymal stem cells (hiPS-MSCs). Moreover, after 8 weeks implantation in mice, this SF-H1/PLCL-HA composite induced bone tissue formation significantly faster than SF/PLCL as indicated by μCT. The present study is the first to demonstrate that release of short hydrophilic peptides derived from CTGF combined with HA potentiated the regenerative capacity for healing critical sized calvarial defect in vivo.

Keywords: Calvarial defect; Connective tissue growth factor; Core-shell nanofibers; Oesteogenesis; Oesteoinductive peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Connective Tissue Growth Factor / administration & dosage*
  • Connective Tissue Growth Factor / chemistry
  • Drug Liberation
  • Durapatite / administration & dosage*
  • Durapatite / chemistry
  • Female
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / drug effects
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mice
  • Osteogenesis / drug effects*
  • Peptides / administration & dosage*
  • Peptides / chemistry
  • Skull / diagnostic imaging
  • Skull / drug effects
  • Skull / physiology
  • X-Ray Microtomography

Substances

  • Peptides
  • Connective Tissue Growth Factor
  • Durapatite