Research Project
7808486
DESCRIPTION (provided by applicant): 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. Once biofilm is established on a medical implant, it is essentially impossible to eradicate by any means except explantation. New technologies that decrease microbial colonization and infection rates associated with metal implants would clearly improve care and reduce medical costs. In Phase I we proposed the development of a generalizable peptide coating, allowing a clinician to load an antibiotic onto an implant at point of care. Using phage display technology, Affinergy has identified a series of peptides that bind with high affinity to metals, including titanium and stainless steel, as well as peptides which bind the antibiotic vancomycin with high affinity. These peptides were synthesized as a single bifunctional peptide to serve as an "interfacial biomaterial" or IFBM designed to attach a coating of vancomycin on the surface of metal implants. The IFBM developed in Phase I retains the high affinity of its component peptides for metals and vancomycin, delivering an effective antimicrobial dosage to metal surfaces. We 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. With the successful completion of our Phase I aims, we are now eager to further optimize our vancomycin-binding sequences, as well as test new vancomycin:metal bifunctional peptides assembled using different ligation chemistries, peptide orientations and asymmetric ratios of peptide components. We will also initiate biocompatibility, storage and sterilization testing of our prototype vancomycin:metal IFBM to ensure this is a commercializable product concept. Finally, we are eager to test our prototype peptide in an in vivo infection model of metal implants. Upon completing these aims, we will have a well-characterized, commercializable antibiotic/peptide coating, ready for a Phase III large animal study likely funded by Affinergy and/or new potential partners. The insights gained from these studies will provide key information for the continued pursuit of a generalizable peptide coating that will promote attachment of antibiotics at point of care to a wide range of medical implants to decrease microbial colonization on their surfaces. 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. Once biofilm-forming bacteria colonize metal hardware, they 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 the continued Phase II development of a generalizable peptide coating that will promote attachment of antibiotics at point of care to a wide range of medical implants to decrease microbial colonization on their surfaces and ultimately lower implant infection rates.
