Inhibition of Staphylococcus epidermidis biofilms using polymerizable vancomycin derivatives.
BACKGROUND
Biofilm formation on indwelling medical devices is a ubiquitous problem causing considerable patient morbidity and mortality. In orthopaedic surgery, this problem is exacerbated by the large number and variety of material types that are implanted. Metallic hardware in conjunction with polymethylmethacrylate (PMMA) bone cement is commonly used.


OBJECTIVE
We asked whether polymerizable derivatives of vancomycin might be useful to (1) surface modify Ti-6Al-4V alloy and to surface/bulk modify PMMA bone cement to prevent Staphylococcus epidermidis biofilm formation and (2) whether the process altered the compressive modulus, yield strength, resilience, and/or fracture strength of cement copolymers.


METHODS
A Ti-6Al-4V alloy was silanized with methacryloxypropyltrimethoxysilane in preparation for subsequent polymer attachment. Surfaces were then coated with polymers formed from PEG(375)-acrylate or a vancomycin-PEG(3400)-PEG(375)-acrylate copolymer. PMMA was loaded with various species, including vancomycin and several polymerizable vancomycin derivatives. To assess antibiofilm properties of these materials, initial bacterial adherence to coated Ti-6Al-4V was determined by scanning electron microscopy (SEM). Biofilm dry mass was determined on PMMA coupons; the compressive mechanical properties were also determined.


RESULTS
SEM showed the vancomycin-PEG(3400)-acrylate-type surface reduced adherent bacteria numbers by approximately fourfold when compared with PEG(375)-acrylate alone. Vancomycin-loading reduced all mechanical properties tested; in contrast, loading a vancomycin-acrylamide derivative restored these deficits but demonstrated no antibiofilm properties. A polymerizable, PEGylated vancomycin derivative reduced biofilm attachment but resulted in inferior cement mechanical properties.


CONCLUSIONS
The approaches presented here may offer new strategies for developing biofilm-resistant orthopaedic materials. Specifically, polymerizable derivatives of traditional antibiotics may allow for direct polymerization into existing materials such as PMMA bone cement while minimizing mechanical property compromise. Questions remain regarding ideal monomer structure(s) that confer biologic and mechanical benefits.
Lawson
McKinley C
MC
Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO, USA. mckinley.lawson@ucdenver.edu
Hoth
Kevin C
KC
Deforest
Cole A
CA
Bowman
Christopher N
CN
Anseth
Kristi S
KS
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D001843:Bone Cements / Q000737:chemistry; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D066298:In Vitro Techniques; D019904:Polymethyl Methacrylate / Q000737:chemistry; D013212:Staphylococcus epidermidis / Q000187:drug effects*; D013530:Surgical Wound Infection / Q000517:prevention & control; D014025:Titanium / Q000737:chemistry; D014640:Vancomycin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001843:Bone Cements; D020099:Coated Materials, Biocompatible; D014640:Vancomycin; D019904:Polymethyl Methacrylate; D014025:Titanium