Functional analysis of bioactivated and antiinfective PDLLA - coated surfaces

J Biomed Mater Res A. 2017 Jun;105(6):1672-1683. doi: 10.1002/jbm.a.36042. Epub 2017 Mar 27.


Common scaffold surfaces such as titanium can have side effects; for example, infections, cytotoxicity, impaired osseointegration, or low regeneration rates for bone tissue. These effects lead to poor implant integration or even implant loss. Therefore, bioactive implants are promising instruments in tissue regeneration. Osteoinductive elements-such as growth factors and anti-infectives-support wound healing and bone growth and thereby enable faster osseointegration, even in elderly patients. In this study, titanium surfaces were coated with a poly-(d,l-lactide) (PDLLA) layer containing different concentrations of copolymer-protected gene vectors (COPROGs) to locally provide bone morphogenetic protein-2 (BMP-2) or activated anti-infective agents, such as chlorhexidine gluconate, triclosan, and metronidazole, to prevent peri-implantitis. The coated titanium implants were then loaded with osteoblasts, NIH 3T3 fibroblasts, and human mesenchymal stem cells in 96-well plates. When shielded by COPROGs as a protective layer and resuspended in PDLLA, BMP-2-encoding pDNA at relatively low doses (5.63 µg/implant) induced the local expression of BMP-2. A linear dose dependence, which is common for recombinant growth factors, was not found, probably due to the retention property of the PDLLA surface. PDLLA, in general, successfully retains additional elements, such as osteoconductive growth factors (BMP-2) and anti-infective agents, which was demonstrated using metronidazole, and thus prevents the systemic application of excessive doses. These bioactive implant surfaces that provide the local release of therapeutic gene vectors or anti-infective agents allow the controlled stimulation of the implant and scaffold osseointegration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1672-1683, 2017.

Keywords: bioactive materials; controlled release; nonviral gene transfer; poly(d,l-lactide); protective copolymer.

MeSH terms

  • Animals
  • Anti-Infective Agents / administration & dosage*
  • Bone Morphogenetic Protein 2 / genetics
  • Coated Materials, Biocompatible / chemistry*
  • Delayed-Action Preparations / chemistry*
  • Drug Delivery Systems / methods
  • Gene Transfer Techniques*
  • Genetic Vectors / genetics
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • NIH 3T3 Cells
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Peri-Implantitis / prevention & control*
  • Polyesters / chemistry*
  • Prostheses and Implants
  • Surface Properties
  • Titanium / chemistry*


  • Anti-Infective Agents
  • Bone Morphogenetic Protein 2
  • Coated Materials, Biocompatible
  • Delayed-Action Preparations
  • Polyesters
  • poly(lactide)
  • Titanium