Phage-bacterium war on polymeric surfaces: can surface-anchored bacteriophages eliminate microbial infections?

These studies illustrate synthetic paths to covalently attach T1 and Φ11 bacteriophages (phages) to inert polymeric surfaces while maintaining the bacteriophage's biological activities capable of killing deadly human pathogens. The first step involved the formation of acid (COOH) groups on polyethylene (PE) and polytetrafluoroethylene (PTFE) surfaces using microwave plasma reactions in the presence of maleic anhydride, followed by covalent attachment of T1 and Φ11 species via primary amine groups. The phages effectively retain their biological activity manifested by a rapid infection with their own DNA and effective destruction of Escherichia coli and Staphylococcus aureus human pathogens. These studies show that simultaneous covalent attachment of two biologically active phages effectively destroy both bacterial colonies and eliminate biofilm formation, thus offering an opportunity for an effective combat against multibacterial colonies as well as surface detections of other pathogens.

Simple click reactions on polymer surfaces leading to antimicrobial behavior.

In this study we developed simple reactions that combined microwave plasma reactions in the presence of maleic anhydride with alkyne click chemistries to achieve a platform for unlimited possibilities for further surface modifications of aliphatic polymer surfaces. Using this approach, we covalently attached ampicillin (AMP) to polyethylene (PE) and polypropylene (PP) substrates. As a result, high efficacy against microbial film formation, manifested by efficient antimicrobial activity against S. aureus with a 97-99.8% decrease of bacterial growth, was achieved. This simple and clean process allows functionalization of any polymeric substrate without adverse effects on bulk polymer properties.

Covalent attachment of multilayers (CAM): a platform for pH switchable antimicrobial and anticoagulant polymeric surfaces.

These studies show covalent attachment of multilayers (CAM) to chemically alter surfaces to achieve pH switchable antimicrobial and anticoagulant properties. Polyethylene (PE), poly(tetrafluoroethylene) (PTFE), and silicon (Si) surfaces were functionalized by tethering pH-responsive "switching" polyelectrolytes consisting of poly(2-vinyl pyridine) (P2VP) and poly(acrylic acid) (PAA) terminated with NH2 and COOH groups, respectively. At pH < 2.3, the P2VP segments are protonated and expended, but at pH > 5.5, they collapse while the PAA segments are expanded. The presence of terminal NH2 or COOH moieties on P2VP and PAA, respectively, facilitated the opportunity for covalently bonding ampicillin (AMP) and heparin (HEP) to both polyelectrolyte chains. Such surfaces, when exposed to S. aureus, inhibit the growth of microbial films (AMP) as well as anticoagulant properties (HEP). Comparison of "dynamic" pH dependent surfaces developed in these studies with "static" surfaces terminated with (AMP) entities shows significant enhancement in the longevity of surface activity against microbial film formation.

Micro-patterning of streptavidin-biotin-ampicillin/heparin on poly(tetrafluoroethylene) (PTFE) surfaces: simultaneous antimicrobial and anticoagulant activity.

Formation of heterogeneous and controllable surface patterns on polymeric materials containing antimicrobial and anticoagulant components represent an attractive way of maintaining synthetic materials "clean" from adverse bio-activities. The primary surface "contaminants" are microbial films as well as blood coagulation, both affecting not only performance of internal or external devices, but often exhibiting detrimental effects on patients. In an effort to simultaneously inhibit formation of microbial films and surface blood coagulation multifunctional assemblies containing streptavidin (STR)-biotin bioconjugates were developed on poly(tetrafluoroethylene) (PTFE) surfaces. Using STR conjugated to a biotin-functionalized PTFE surface, spatially controlled micro-patterning was produced by grafting biotinylated polyethylene glycol (B-PEG) to COOH modified PTFE (MA-PTFE), followed by inkjet micro-printing of biotinylated ampicillin (B-AM) and biotinylated heparin (B-HP) molecules. These surfaces exhibit simultaneous antimicrobial and anticoagulant attributes manifested by "zone of inhibition" and anticoagulant measurements. Quantitative spectroscopic analysis revealed that the required surface density of COOH groups on PTFE is 2.94 × 10-7 g cm-2, and B-PEG and STR densities of 9.2 × 10-8 g cm-2 and 3.5 × 10-8 g cm-2, respectively, are sufficient to achieve simultaneous antimicrobial and anticoagulant responses. These studies also showed that the force required to remove STR-biotin conjugates attached to PTFE surfaces measured by atomic force microscopy is approximately 1090 pN, thus providing desirable surface mechanical stability.