Development of severe bacterial infections is a serious complication in all implant-inserting surgeries. It is associated with considerable morbidity and costs. Solution of this problem requires development of new implant materials that would demonstrate a strong antimicrobial activity without toxic effects on host tissues. Our central hypothesis is that non-antibiotic, UV and visible light resistant silver(I) complexes with strong antimicrobial effect offer such benefits when used either as an adjunct or alternative material. Therefore the goal of the proposed research it to study the ten newly synthesized silver(I) cyanoximates and examine their antimicrobial effect on bacterial adhesion and biofilm formation. Inertness of these compounds towards intense UV and visible light will allow their application as additives to the light curable polymeric composites used in joint replacement therapy and dental implants insertions. Since bacterial adhesion and biofilm formation are important predisposing factors in the development of implant infections, the inhibitory effect of the silver(I) complexes on their development will enable application of the silver(I) cyanoximates as new antimicrobial surfaces. The goal will be achieved by accomplishing the following specific aims: (1) synthesize series of novel silver(I) cyanoximates in sufficient for further studies quantities and test their thermal stability;(2) prepare solid polymeric composites containing different mass % of silver(I) cyanoximates and shape them as cylinders and plates, and also deposit them as films onto the surface of ceramics and metals (Ag, Co, Ni) for further antimicrobial studies;(3) identify and quantitatively characterize the effect of silver(I) cyanoximate-coated surfaces on bacterial adhesion and biofilm formation of P. aeruginosa, S. aureus and S. mutans. The proposed research is innovative since it will be the first systematic and rigorous test of antimicrobial effect of the new light resistant silver(I) complexes on bacterial adhesion and biofilm formation. We expect to have identified the most effective compound that may be offered for further in vivo testing. This study will have a significant impact on the development of new methods of preventing bacterial infections caused by surgical introduction of prosthetic joints and implants. The proposed research is interdisciplinary project between chemistry and microbiology. It will involve two graduate students and three undergraduate students from both institutions, and will provide valuable "hands-on" training in research and discovery process in the areas of modern bio-inorganic chemistry, microbiology and biomedical research. The research experience that students would receive working on the project will significantly impact the development of their professional careers.

Public Health Relevance

Infection of medical implanted materials is a common complication of implant insertions and is associated with considerable morbidity and costs. Therefore there is a critical need for developing new implant materials that would prevent post-surgical infections. Such compounds are required to inhibit bacterial growth, but not to exhibit toxic effect towards human tissues. The proposed research will synthesize a series of new non-antibiotic, silver(I) cyanoximates, which are UV and visible light resistant compounds and exhibit a significant antimicrobial effect on bacterial adhesion and biofilm formation. The resistance of these compounds towards UV and visible light will allow their application as additives to UV-radiation curable polymeric composites in joint replacement therapy and dental implants insertions. Their antimicrobial effect will enable their application in preventing implant associated infections, while thermal stability will allow sterilization of coated indwelling devises. The proposed research is an interdisciplinary project between chemistry and microbiology departments of two state institutions. This project will involve two graduate students and three undergraduate students, and will provide valuable hands-on training in research and discovery process in the areas of modern bio-inorganic chemistry, microbiology and biomedical research.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
3R15AI088594-01A1S1
Application #
8671602
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Xu, Zuoyu
Project Start
2012-03-01
Project End
2015-02-28
Budget Start
2013-07-01
Budget End
2015-02-28
Support Year
1
Fiscal Year
2013
Total Cost
$26,862
Indirect Cost
$8,438
Name
Missouri State University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
076255876
City
Springfield
State
MO
Country
United States
Zip Code
65897
Riddles, Courtney N; Whited, Mark; Lotlikar, Shalaka R et al. (2014) Synthesis and Characterization of Two Cyanoxime Ligands, Their Precursors, and Light Insensitive Antimicrobial Silver(I) Cyanoximates. Inorganica Chim Acta 412:94-103