Polymerizable Vancomycin Derivatives for Bactericidal Biomaterial Surface Modification: Structure-Function Evaluation

Surface modification of implantable biomaterials with biologically active functionalities, including antimicrobials, has wide potential for addressing implant-related design problems. Here, four polymerizable vancomycin derivatives bearing either acrylamide or poly(ethylene glycol) (PEG)-acrylate were synthesized and then polymerized through a surface-mediated reaction. Functionalization of vancomycin at either the V-3 or the X-1 position decreased monomeric activity by 6-75-fold depending on the modification site and the nature of the adduct (P < 0.08 for all comparisons). A 5000 Da PEG chain showed an order of magnitude decrease in activity relative to a 3400 Da counterpart. Molecular dynamics computational simulations were used to explore the mechanisms of this decreased activity. Assays were also conducted to demonstrate the utility of a living radical photopolymerization to create functional, polymeric surfaces with these monomers and to demonstrate surface-based activity against Staphylococcus epidermidis. In particular, the vancomycin-PEG-acrylate derivatives demonstrated a 7-8 log reduction in bacterial colony forming units (CFU) with respect to nonfunctionalized control surfaces.