The effects of Sr-incorporated micro/nano rough titanium surface on rBMSC migration and osteogenic differentiation for rapid osteointegration

Biomater Sci. 2018 Jun 25;6(7):1946-1961. doi: 10.1039/c8bm00473k.

Abstract

Recruitment of endogenous bone marrow-derived mesenchymal stem cells (BMSCs) has been widely discussed as an alternative strategy for bone regeneration. Strontium (Sr) is known to direct the BMSCs' commitment to the bone lineage and encourage bone formation; however, the underlying mechanisms remain elusive. In this study, an Sr-incorporated micro/nano rough titanium surface (MNT-Sr) was fabricated by hydrothermal treatment in an attempt to facilitate BMSCs' recruitment and their osteogenic differentiation to enhance rapid osseointegration. Micro rough titanium (MT) was set as the control biomaterial. In vitro, MNT-Sr and its extracts promoted the migration and osteogenic differentiation of BMSCs. In animal studies, green fluorescent protein (GFP)-labeled BMSCs were intravenously injected into wild-type rats for tracing before tibial implantation surgery. The GFP+BMSC recruitment to the implantation site was successfully triggered by MNT-Sr implantation. A trend for increased bone area (BA%), bone-implant contact (BIC%) and removal torque values (RTVs) was observed for the MNT-Sr implant compared to that observed for MT at 2 weeks. Advanced mechanism analysis indicated that Sr2+ enhanced the SDF-1α/CXCR4 signaling pathway both in vitro and in vivo. Taken together, these findings suggest that MNT-Sr has promising therapeutic potential for future use in dental implants by homing endogenous stem cells to stimulate bone regeneration.

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology*
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Bone-Implant Interface
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Cells, Cultured
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / metabolism
  • Gene Expression Regulation
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Osseointegration / drug effects*
  • Osseointegration / genetics
  • Osteogenesis / drug effects*
  • Osteogenesis / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism
  • Signal Transduction
  • Strontium / chemistry
  • Strontium / pharmacology*
  • Tibia / drug effects
  • Tibia / surgery
  • Titanium / chemistry
  • Titanium / pharmacology*

Substances

  • Biocompatible Materials
  • CXCL12 protein, rat
  • Chemokine CXCL12
  • Cxcr4 protein, rat
  • Receptors, CXCR4
  • Green Fluorescent Proteins
  • Titanium
  • Strontium