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. New technologies that decrease microbial colonization of metal implants would reduce these infections, mitigating their severe consequences. Affinergy is developing bifunctional affinity peptides, called interfacial biomaterials (IFBMs), that promote the attachment and retention of drugs, proteins, and cells on the surface of medical devices. Using phage display, we have identified specific peptide sequences that bind with high affinity to a number of metals and another specific set of peptide sequences that bind with high affinity to vancomycin. Synthesizing these sequences as a single IFBM using appropriate linkers permits the attachment of vancomycin directly to the surface of a metal implant at point-of-care. Thus far however, Affinergy's drug delivery coatings have been limited to arranging a 1-to-1 interaction between a peptide molecule and an antibiotic. While we have observed promising preliminary data with this technique using antibiotics, there are likely additional drugs we might target if the amount of drug loaded to a given surface could be increased. Because our coatings are comprised of high affinity peptides, expanding our technology using an approach which employs the structural and chemical properties of peptides would be desirable. We therefore propose here the coupling of our material and drug-binding peptides to sequences which assemble into higher-order nanostructures. Our goal is to generate a three-dimensional surface coating from self-assembling affinity peptides, capable of binding and retaining significantly higher concentrations of a drug to a device surface. Data from our preliminary studies, suggest that peptides capable of limited self-assembly bind to materials with improved resistance to chemical challengers compared to traditional IFBMs. This research program attempts to continue these studies, toward developing a self assembling coating system, attaching vancomycin to metal.
In Aim 1, we will synthesize and characterize vancomycin and metal binding peptides with the addition of various self-assembling peptide sequences.
In Aim 2, we will characterize the biochemical and biophysical nature of self-assembling affinity peptides in solution and on metal surfaces. We will compare the loading density, on-rate, and release of vancomycin from metal coated with traditional IFBMs and new self-assembling affinity peptides. Finally, in Aim 3, we will characterize the anti-microbial activity of vancomycin linked to metals with traditional IFBMs and self-assembling affinity peptides. Successful completion of these aims would encourage us to expand self-assembling affinity peptides to other clinical applications utilizing additional combinations of Affinergy drug, protein, cell, and material affinity peptides. ? ? Public Health Relevance: 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 self-assembling affinity peptide coating that will promote attachment of antibiotics at point of care to a wide range of metal implants to decrease microbial colonization on their surfaces. ? ? ?
