Bi-functionalization of a calcium phosphate-coated titanium surface with slow-release simvastatin and metronidazole to provide antibacterial activities and pro-osteodifferentiation capabilities

PLoS One. 2014 May 20;9(5):e97741. doi: 10.1371/journal.pone.0097741. eCollection 2014.

Abstract

Coating the surface of titanium implants or other bone graft substitute materials with calcium phosphate (Ca-P) crystals is an effective way to enhance the osteoconduction of the implants. Ca-P coating alone cannot confer pro-osteodifferentiation and antibacterial capabilities on implants; however, it can serve as a carrier for biological agents which could improve the performance of implants and bone substitutes. Here, we constructed a novel, bi-functional Ca-P coating with combined pro-osteodifferentiation and antibacterial capabilities. Different concentrations of metronidazole (MNZ) and simvastatin (SIM) were integrated into biomimetic Ca-P coatings on the surface of titanium disks. The biological effects of this bi-functional biomimetic coating on human bone marrow mesenchymal stem cells (hBMMSCs), human adipose derived stromal cells (hASCs), and Porphyromonas gingivalis were assessed in vitro. We observed that Ca-P coatings loaded with both SIM and MNZ display favorable release kinetics without affecting cell proliferation or attachment. In the inhibition zone test, we found that the bi-functional coating showed lasting antibacterial effects when incubated with Porphyromonas gingivalis for 2 and 4 days. Moreover, the osteodifferentiation of hBMMSCs and hASCs were increased when cultured on this bi-functional coating for 7 and 14 days. Both drugs were loaded onto the Ca-P coating at specific concentrations (10(-5) M SIM; 10(-2) M MNZ) to achieve optimal release kinetics. Considering the safety, stability and low cost of SIM and MNZ, this novel bi-functional Ca-P coating technique represents a promising method to improve the performance of metal implants or other bone substitute materials, and can theoretically be easily translated to clinical applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / chemistry
  • Calcium Phosphates* / chemistry
  • Cell Adhesion
  • Cell Culture Techniques
  • Cell Differentiation
  • Cell Proliferation
  • Coated Materials, Biocompatible*
  • Delayed-Action Preparations*
  • Disk Diffusion Antimicrobial Tests
  • Humans
  • Kinetics
  • Mesenchymal Stem Cells / cytology
  • Metronidazole / administration & dosage*
  • Metronidazole / chemistry
  • Osteogenesis
  • Prostheses and Implants
  • Simvastatin / administration & dosage*
  • Simvastatin / chemistry
  • Surface Properties
  • Titanium* / chemistry

Substances

  • Anti-Bacterial Agents
  • Calcium Phosphates
  • Coated Materials, Biocompatible
  • Delayed-Action Preparations
  • Metronidazole
  • calcium phosphate
  • Simvastatin
  • Titanium

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (No. 30901693, No. 81170937), http://www.nsfc.gov.cn/Portal0/default152.htm. This study was also supported by the Program for New Century Excellent Talents in University from Ministry of Education (BMU20110274), http://www.moe.edu.cn/publicfiles/business/htmlfiles/moe/A16/index.html. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.