Osteostatin-coated porous titanium can improve early bone regeneration of cortical bone defects in rats

Tissue Eng Part A. 2015 May;21(9-10):1495-506. doi: 10.1089/ten.TEA.2014.0476. Epub 2015 Mar 10.

Abstract

A promising bone graft substitute is porous titanium. Porous titanium, produced by selective laser melting (SLM), can be made as a completely open porous and load-bearing scaffold that facilitates bone regeneration through osteoconduction. In this study, the bone regenerative capacity of porous titanium is improved with a coating of osteostatin, an osteoinductive peptide that consists of the 107-111 domain of the parathyroid hormone (PTH)-related protein (PTHrP), and the effects of this osteostatin coating on bone regeneration were evaluated in vitro and in vivo. SLM-produced porous titanium received an alkali-acid-heat treatment and was coated with osteostatin through soaking in a 100 nM solution for 24 h or left uncoated. Osteostatin-coated scaffolds contained ∼0.1 μg peptide/g titanium, and in vitro 81% was released within 24 h. Human periosteum-derived osteoprogenitor cells cultured on osteostatin-coated scaffolds did not induce significant changes in osteogenic (alkaline phosphatase [ALP], collagen type 1 [Col1], osteocalcin [OCN], runt-related transcription factor 2 [Runx2]), or angiogenic (vascular endothelial growth factor [VEGF]) gene expression; however, it resulted in an upregulation of osteoprotegerin (OPG) gene expression after 24 h and a lower receptor activator of nuclear factor kappa-B ligand (RankL):OPG mRNA ratio. In vivo, osteostatin-coated, porous titanium implants increased bone regeneration in critical-sized cortical bone defects (p=0.005). Bone regeneration proceeded until 12 weeks, and femurs grafted with osteostatin-coated implants and uncoated implants recovered, respectively, 66% and 53% of the original femur torque strength (97±31 and 77±53 N·mm, not significant). In conclusion, the osteostatin coating improved bone regeneration of porous titanium. This effect was initiated after a short burst release and might be related to the observed in vitro upregulation of OPG gene expression by osteostatin in osteoprogenitor cells. Long-term beneficial effects of osteostatin-coated, porous titanium implants on bone regeneration or mechanical strength were not established here and may require optimization of the pace and dose of osteostatin release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Biomechanical Phenomena / drug effects
  • Bone Regeneration / drug effects*
  • Cell Adhesion / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coated Materials, Biocompatible / pharmacology*
  • Femur / diagnostic imaging
  • Femur / drug effects
  • Femur / pathology*
  • Femur / physiopathology*
  • Gene Expression Regulation / drug effects
  • Humans
  • Male
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / genetics
  • Osteoblasts / drug effects
  • Osteoblasts / pathology
  • Osteoclasts / drug effects
  • Osteoclasts / pathology
  • Parathyroid Hormone-Related Protein / pharmacology*
  • Peptide Fragments / pharmacology*
  • Porosity
  • Rats, Wistar
  • Titanium / pharmacology*
  • X-Ray Microtomography

Substances

  • Coated Materials, Biocompatible
  • Parathyroid Hormone-Related Protein
  • Peptide Fragments
  • parathyroid hormone-related protein (107-111)
  • Titanium