Covalent Attachment of N,N-Dodecyl,Methyl-Polyethylenimine to Boston Keratoprosthesis Materials Inhibits S. aureus Biofilm Formation Without Cytotoxicity or Corneal Cell Reactivity

Abstract

Purpose: : To minimize bacterial adherence and biofilm formation by comparative analysis of new polycations bound to bio-prosthetic ocular-associated materials, particularly poly (methyl methacrylate) (PMMA), using the Boston Keratoprosthesis as a model system.

Methods: : Quantitative assessments of S. aureus microbial biofilm formation by a linear version of N, N-dodecyl, methyl-polyethyleneimine (DMPEI) (217 kDa) covalently bound to PMMA (DMPEI-PMMA) compared to PMMA respectively was performed. DMPEI-bound materials compared to the unbound original materials were screened for corneal reactivity in both cell tissue culture and in vivo in the rabbit. By using a newly developed intrastromal infection model in the rodent, the antimicrobial efficacy of DMPEI-PMMA compared to parent PMMA is being determined.

Results: : There is an inhibitory effect on S. aureus biofilm formation by DMPEI-derivatized materials compared to the parent PMMA. DMPEI-PMMA did not confer any additional epithelial cell cytotoxicity in vitro nor corneal reactivity in vivo in the rabbit. Assessment of the antimicrobial efficacy of DMPEI-PMMA in an intrastromal infection model in rodent species is ongoing.

Conclusions: : We found that covalent derivatization with DMPEI of PMMA greatly reduces S. aureus biofilm formation compared to the parent materials in vitro. There is no additional cytotoxicity seen in either a human corneal epithelial cell tissue culture model or an intrastromal rabbit model in vivo. Ongoing studies are evaluating DMPEI-derivatized materials for in vivo antimicrobial efficacy in a new intrastromal infection model in rodent species.

Keywords: Staphylococcus • keratoprostheses • microbial pathogenesis: experimental studies