Nanohybrid Composites Minimize Antibiotic Resistant Infections - PROJECT SUMMARY/ABSTRACT: Open fractures are frequently (more than 150,000 cases in the U.S. every year) seen and have high (~10%) infection rates. Open fracture-associated infections are clinically devastating, and have led to reduced limb function, secondary operations, delayed union/nonunion, and death. Infection has led to significantly high costs in healthcare, resulting in approximately $500 million of additional costs in managing open fractures each year in the U.S. Further complicating the problem, alarmingly high percentages (e.g., 32.2% for tibial fractures) of open fracture infections are associated with antibiotic resistant bacteria, which have led to a two-fold increase in morbidity and mortality, and have made the drug choices for infection management increasingly limited. The long-term goal of this application is to develop translational strategies to prevent or treat bone infections in clinical settings. The objective of this project is to develop safe antimicrobial nanohybrid methods to reduce antibiotic resistant infections in open fractures. The central hypothesis is that nanohybriding two unique antimicrobial materials with different dimensions at the nanometer scale will synergistically enhance antimicrobial properties and significantly reduce host toxicity. There are three specific aims: (i) To test the hypothesis that innovative silver nanoparticle-carbon nanotube (AgNP-CNT) nanohybrids present high antimicrobial properties against various bacteria seen in open fractures and low toxicity toward cells important to bone. (ii) To test the hypothesis that AgNP-CNT nanohybrids present high antimicrobial properties and low host toxicity in preventing antibiotic resistant infections in an animal model. (iii) To test the hypothesis that bioengineering AgNP-CNT nanohybrids on implant surfaces enhances preclinical outcomes. Specifically, the in vitro antimicrobial properties of AgNP-CNT nanohybrids will be tested against a variety of bacteria and their cytotoxicity properties toward multiple human cells will be determined. The nanohybrids will be tested in an open femur fracture rat model to assess their effects on infection, healing, and host toxicity. Moreover, the nanohybrids will be bioengineered on orthopaedic implants and their coatings will be tested both in vitro and in vivo; delivering antimicrobials at the implant surface is expected to achieve high antimicrobial levels at the right place to minimize systemic toxicity. This project will contribute new knowledge on how hybriding two materials with different dimensions at the nanometer scale may synergistically increase antimicrobial properties and reduce host toxicity. The expected outcome is a biologically safe, nanotechnology-based strategy that will drive and broaden the safe use of silver and carbon nanotubes for local biomedical applications (e.g., open fracture fixation). The nanohybrids may be engineered on various medical products – ranging from bone grafts, dental implants, and catheters, to bandages and needles – to reduce infections while improving recovery.
