Infection surrounding metal implants 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. The biofilm bacteria that establish themselves on implants are essentially impossible to eradicate by any means except explantation. New technologies that decrease microbial colonization and infection rates associated with metal implants would clearly benefit society. We propose to develop a generalizable peptide coating that will allow a clinician to choose from more than one class of antibiotics to load onto an implant at point of care. Using phage display technology, Affinergy has identified a series of peptides that bind with high affinity to a number of metals, including titanium and stainless steel. These metal-binding peptides will serve as the basis for engineering an antibiotic binding, peptide coating. The goal of this Phase I SBIR proposal is to validate an """"""""Interfacial Biomaterials"""""""" (IFBM) approach to attach an antibiotic onto metal implant surfaces to decrease implant colonization. We initially targeted vancomycin for """"""""proof of principle"""""""" because it has a significant amount of structural complexity. This complexity provides a larger """"""""chemical space"""""""" from which a binding peptide can be found; making the success of phage display panning more likely within a short time frame.
In aim 1, we will synthesize candidate peptides that have binding affinity for vancomycin.
In aim 2, we will synthesize a series of vancomycin:metal IFBM's. We will verify the stability of these candidate IFBM's in biological fluids, test their ability to bind and retain antibiotics, verify that they do not inhibit osteoblast attachment, and quantify the coating density of peptide and antibiotic on metal surfaces.
In aim 3, we will characterize the anti-microbial activity and release kinetics of vancomycin bound and released from peptide coated metal. If successful, Phase II work would involve biopanning of two more antibiotics targets (an aminoglycoside and a tetracycline) commonly used both locally and systemically to prevent or treat implant associated infections. Branched IFBM's containing binding modules for all three classes of antibiotic would be assembled and examined for efficacy in vitro and then in an implant infection model in vivo. ? ? Infection surrounding metal hardware is a common and sometimes devastating cause of implant failure in a number of medical fields including oral, craniomaxillofacial (CMF), orthopedic, and cardiovascular surgery. Arising from the establishment of pathogenic biofilms on device surfaces, these infections not only necessitate new surgeries but in themselves present a significant threat to life and limb. The biofilm bacteria that establish themselves on metal hardware are essentially impossible to eradicate by any means except explantation. Methods that decrease infection rates associated with metal implants would clearly benefit society. We propose to develop a generalizable peptide coating that will promote attachment of multiple antibiotics at point of care to a wide range of metal implants to decrease microbial colonization on their surfaces and ultimately lower implant infection rates. ? ? ?
