Improved anchorage of Ti6Al4V orthopaedic bone implants through oligonucleotide mediated immobilization of BMP-2 in osteoporotic rats

PLoS One. 2014 Jan 21;9(1):e86151. doi: 10.1371/journal.pone.0086151. eCollection 2014.

Abstract

The aim of the present study was to test the biocompatibility and functionality of orthopaedic bone implants with immobilized oligonucleotides serving as anchor stands for rhBMP-2 and rhVEGF-A conjugated with complementary oligonucleotides in an osteoporotic rat model. Al2O3-blasted acid etched Ti6Al4V implants, carrying oligonucleotide anchor strands and hybridized with rhBMP-2 or rhVEGF-A through complementary 31-mer oligonucleotide stands were inserted into the proximal tibia of ovariectomized rats. At the time of surgery (15 weeks after ovariectomy) microCT analysis showed significantly lower bone mineral density compared to non-ovariectomized animals. Bone-implant contact (BIC) and pullout-force were not negatively affected by non-hybridized anchor strands. Twelve weeks after surgery, a significantly higher pullout force was found for BMP-2 hybridized to the anchor strands compared to non-hybridized anchor strands or native samples, and on histomorphometric analysis BIC was highest in the BMP group. Thus, we could show the biocompatibility and in vivo functionality of this modular, self-organizing system for immobilization and subsequent release of BMP-2 in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alloys
  • Animals
  • Biomechanical Phenomena / drug effects
  • Bone Density / drug effects
  • Bone Morphogenetic Protein 2 / metabolism*
  • Female
  • Humans
  • Immobilized Proteins / metabolism*
  • Implants, Experimental*
  • Microscopy, Electron, Scanning
  • Oligonucleotides / metabolism*
  • Orthopedics
  • Osteoporosis / diagnostic imaging
  • Osteoporosis / physiopathology
  • Osteoporosis / therapy*
  • Rats
  • Rats, Wistar
  • Recombinant Proteins / metabolism
  • Surface Properties
  • Tibia / diagnostic imaging
  • Tibia / drug effects
  • Tibia / pathology*
  • Tibia / physiopathology
  • Titanium / pharmacology*
  • Transforming Growth Factor beta / metabolism*
  • X-Ray Microtomography

Substances

  • Alloys
  • Bone Morphogenetic Protein 2
  • Immobilized Proteins
  • Oligonucleotides
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2
  • titanium alloy (TiAl6V4)
  • Titanium

Grants and funding

This work has been funded by a grant from the German Federal Ministry of Education and Research (BMBF, FKZ 13N1006). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.