Fusion peptide P15-CSP shows antibiofilm activity and pro-osteogenic activity when deposited as a coating on hydrophilic but not hydrophobic surfaces

J Biomed Mater Res A. 2015 Dec;103(12):3736-46. doi: 10.1002/jbm.a.35511. Epub 2015 Jun 11.

Abstract

In the context of porous bone void filler for oral bone reconstruction, peptides that suppress microbial growth and promote osteoblast function could be used to enhance the performance of a porous bone void filler. We tested the hypothesis that P15-CSP, a novel fusion peptide containing collagen-mimetic osteogenic peptide P15, and competence-stimulating peptide (CSP), a cationic antimicrobial peptide, has emerging properties not shared by P15 or CSP alone. Peptide-coated surfaces were tested for antimicrobial activity toward Streptoccocus mutans, and their ability to promote human mesenchymal stem cell (MSC) attachment, spreading, metabolism, and osteogenesis. In the osteogenesis assay, peptides were coated on tissue culture plastic and on thin films generated by plasma-enhanced chemical vapor deposition to have hydrophilic or hydrophobic character (water contact angles 63°, 42°, and 92°, respectively). S. mutans planktonic growth was specifically inhibited by CSP, whereas biofilm formation was inhibited by P15-CSP. MSC adhesion and actin stress fiber formation was strongly enhanced by CSP, P15-CSP, and fibronectin coatings and modestly enhanced by P15 versus uncoated surfaces. Metabolic assays revealed that CSP was slightly cytotoxic to MSCs. MSCs developed alkaline phosphatase activity on all surfaces, with or without peptide coatings, and consistently deposited the most biomineralized matrix on hydrophilic surfaces coated with P15-CSP. Hydrophobic thin films completely suppressed MSC biomineralization, consistent with previous findings of suppressed osteogenesis on hydrophobic bioplastics. Collective data in this study provide new evidence that P15-CSP has unique dual capacity to suppress biofilm formation, and to enhance osteogenic activity as a coating on hydrophilic surfaces.

Keywords: biofilm; biomimetic peptide; biomineralization; cell adhesion; mesenchymal stem cell; osteogenesis; plasma-enhanced chemical vapor deposition; wettability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antimicrobial Cationic Peptides / administration & dosage
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology*
  • Bacterial Proteins / administration & dosage
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / pharmacology
  • Biofilms / drug effects*
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Cells, Cultured
  • Coated Materials, Biocompatible / chemistry*
  • Collagen / administration & dosage
  • Collagen / chemistry
  • Collagen / pharmacology*
  • DNA-Binding Proteins / administration & dosage
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / pharmacology
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Molecular Sequence Data
  • Osteogenesis / drug effects*
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / pharmacology
  • Streptococcal Infections / prevention & control
  • Streptococcus / drug effects*
  • Streptococcus / physiology
  • Wettability

Substances

  • Antimicrobial Cationic Peptides
  • Bacterial Proteins
  • Coated Materials, Biocompatible
  • ComA protein, Bacteria
  • DNA-Binding Proteins
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • cell-binding peptide P-15
  • Collagen