Prevention of Medical Implant Infection through Self-Assembled Engineered Peptides as Surface Active Bio-Agents

Abstract

Titanium medical implants have revolutionized health care in treating bone and joint degeneration, neoplasms and inflammation. Due to their biocompatibility, mechanical strength, and non-corrosive properties, titanium and titanium alloys are among the most common materials used in medical and dental implants. Despite improvements in implant technology, including prophylactic therapy, failure attributed to infection is as high as 7.5% of total hip arthroplasty, 14.8% of total knee arthroplasty, and 8% of dental implants. In the first hours following surgery the implant surface is most vulnerable to bacterial colonization and the bacterial pathogens are also most susceptible to antimicrobial treatment. We demonstrate the design and application of a bifunctional peptide film composed of a titanium anchoring domain linked to an antimicrobial peptide domain through an engineered spacer for prevention and treatment of medical implant infections. To overcome challenges with preserving anchoring and antimicrobial domain function, we propose a spacer design to reduce inter-domain interference and improve function based on understanding the peptide structure/function relationship. This innovative approach overcomes challenges faced with rising numbers of antibiotic resistance bacterial strains, by providing a localized and robust antimicrobial and antifouling effect. Our studies aim to enhance the bifunctional peptide design by incorporating different functional domains using a predictive design approach. Along with these studies, we designed peptides based upon structure-function relationship, characterized their individual functions, and proposed design criteria for effective surface functionalization of the peptide films. Finally, we test the proposed approach as a retreatment option for various stages of peri-implant disease, which is a major unsolved problem in dentistry leading to dental implant failure.