Using Bifunctional Peptides Capable of Delivering Antibiotics to Biomaterials as Medical Device Coatings

摘要

Infection surrounding surgically implanted medical devices is a common and sometimes devastating cause of implant failure in a number of fields including oral, craniomaxillofacial (CMF), orthopedic, and cardiovascular surgery. These infections, which arise from the establishment of biofilms on device surfaces, not only necessitate new surgeries but in themselves present a significant threat to life and limb. Once biofilm is established on a medical implant, it is essentially impossible to eradicate by any means except explantation. In fact, surgical wounds are often infected through a similar mechanism involving bacterial colonization of the tissues exposed during surgery. New technologies that decrease microbial colonization - and subsequently infection rates associated with metal implants and surgical sites - would clearly improve care and reduce medical costs. Affinergy has developed a series of generalizable medical device coatings, intended to allow a clinician to load an antibiotic onto an implant at the point of care, immediately prior to implantation. These coating peptides are identified through a laboratory technique called phage display technology. Using this technique, Affinergy has identified a series of peptides that bind with high affinity to various materials including plastics and metals. In addition, peptide sequences have been isolated and optimized which bind the antibiotic vancomycin with high affinity. Vancomycin-binding peptides have been paired with biomaterial-binding peptides to generate a single bifunctional peptide designed to attach vancomycin to the surface of implanted devices. Our leading peptide, capable of linking vancomycin to metal surfaces, retains the high affinity of its component peptides for metals and vancomycin, respectively, and delivers an effective antimicrobial dosage to metal surfaces. We have also demonstrated that this peptide coating for metal surfaces is stable in biological fluids, resists biomechanical and shear stress and does not alter cellular behavior on metal implants.