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

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• 作者：McKinley C. Lawson ; Richard Shoemaker ; Kevin B. Hoth ; Christopher N. Bowman ; Kristi S. Anseth
• 刊名：Biomacromolecules
• 出版年：2009
• 出版时间：August 10, 2009
• 年：2009
• 卷：10
• 期：8
• 页码：2221-2234
• 全文大小：470K
• 年卷期：v.10,no.8(August 10, 2009)
• ISSN：1526-4602

文摘

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 V₃ or the X₁ 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.