Multifunctional sulfonated polyetheretherketone coating with beta-defensin-14 for yielding durable and broad-spectrum antibacterial activity and osseointegration

Acta Biomater. 2019 Mar 1:86:323-337. doi: 10.1016/j.actbio.2019.01.016. Epub 2019 Jan 11.

Abstract

To address periprosthetic joint infection (PJI), a formidable complication after joint arthroplasty, an implant with excellent osseointegration and effective antibacterial activity has being extensively pursued and developed. In this work, the mouse beta-defensin-14 (MBD-14) was immobilized on the polyetheretherketone (PEEK) surface with three-dimensional (3D) porous structure to improve its antibacterial activity and osseointegration. An in vitro antibacterial evaluation showed that the porous PEEK loaded with MBD-14 wages a durable and effective fight against both Staphylococcus aureus (gram-positive) and Pseudomonas aeruginosa (gram-negative). In addition to the superior antibacterial activity, we found that the enhanced proliferation and osteogenic differentiation of bone mesenchymal stem cells were verified through various in vitro analyses. To evaluate the in vivo bactericidal effect and osseointegration of the samples, the rat femoral models with infection and non-infection were established. The enhanced osseointegration of the MBD-14-loaded samples was found in both two in vivo models. And no bacteria survived on the surfaces of samples with a relatively high MBD-14 concentration. Above results indicate that the 3D porous PEEK coating loaded with MBD-14 simultaneously yields excellent osseointegration while exerting durable and broad-spectrum antibacterial activity. And it paves the way for PEEK to be applied clinically to address PJI. STATEMENT OF SIGNIFICANCE: (1). By using the physio-chemical technique including sulfonation and lyophilization etc., a three-dimensional porous network is developed on polyetheretherketone (PEEK) surface, in which mouse beta-defensin-14 (MBD-14, a broad-spectrum antimicrobial peptide) is then loaded. It endows PEEK with antibacterial activity and osseointegration. (2). Two in vivo animal models with infection and non-infection are used to prove the new bone formation around the samples. (3). Supplementary material also proves that MBD-14 promotes the osteogenic differentiation of BMSCs. However, its potential mechanism needs to be further studied in future. (4). The modified PEEK, including excellent osseointegration and a durable and broad-spectrum antibacterial activity, could be applied clinically to address PJI which is a hot potato for surgeons and patients undergoing total joint arthroplasty.

Keywords: Antibacterial activity; Beta-defensin-14; Osseointegration; Periprosthetic joint infection; Polyetheretherketone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Benzophenones
  • Cells, Cultured
  • Cytoskeleton / drug effects
  • Cytoskeleton / metabolism
  • Female
  • Femur / diagnostic imaging
  • Femur / drug effects
  • Femur / pathology
  • Gene Expression Regulation / drug effects
  • Ketones / chemistry*
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Microbial Sensitivity Tests
  • Osseointegration / drug effects*
  • Osteogenesis / drug effects
  • Polyethylene Glycols / chemistry*
  • Polymers
  • Pseudomonas aeruginosa / drug effects
  • Rats, Sprague-Dawley
  • Staphylococcus aureus / drug effects
  • Sulfonic Acids / chemistry*
  • beta-Defensins / chemistry*

Substances

  • Anti-Bacterial Agents
  • Benzophenones
  • Ketones
  • Polymers
  • Sulfonic Acids
  • beta-Defensins
  • polyetheretherketone
  • Polyethylene Glycols