Compositions containing one or more types of membrane-targeting
antimicrobial agents immobilized on a substrate with activity in relevant biological environments, and methods of making and using thereof, are described herein. The
antimicrobial agents retain their activity in the presence of
blood proteins and / or
in vivo due to improved molecular structures which allow for cooperative action of immobilized agents and hydrophilic chemistries which
resist non-
specific protein adsorption. Suitable molecular structures include branched structures, such as dendrimers and randomly branched polymers. The molecule structures may also include hydrophilic tethers which provide both flexibility and resistance to non-
specific protein adsorption. The membrane targeting
antimicrobial agent coatings can be applied to a variety of different types of substrates including medical implants such as vascular grafts,
orthopedic devices,
dialysis access grafts, and catheters; surgical tools, surgical garments; and bandages. The substrates can be composed of
metallic materials, ceramics, polymers, fibers,
inert materials such as
silicon, and combinations thereof. The compositions described herein are substantially non-leaching, resistant to non-
specific protein adsorption, and non-hemolytic.