Inflammation-Responsive Antibiotic Coatings for Prophylactic Bacterial Infection Treatment in Orthopaedic Reconstructions
Abstract
Bacterial bone infections are highly destructive pathologies that especially affect military Service Members and civilians following orthopedic trauma injuries. In particular, blast injuries suffered by Soldiers during combat tours often result in open, complex fractures that are susceptible to both initial and recurrent bacterial infections even with treatment. Some recent technologies have attempted to locally deliver antibiotics to surgically reconstructed bone through drug-loaded cements, but these systems have typically been limited by poorly controlled drug release kinetics that often misalign with disease progression or infection recurrence events. To directly address these shortcomings and create a system with sustained antibiotic delivery in bone healing applications, this proposal outlines the creation of drug coatings on the surface of bone implants that selectively release antimicrobials in response to bacterial infections. This specifically triggered system will discharge antibacterial therapies only when needed, thereby significantly extending the drug delivery window of local antibiotic treatments by creating on-demand drug release for combating bacterial re-infection. This responsive technology efficiently falls within the FY21 PRMRP Topic Area of Sustained Release Drug Delivery by offering an innovative strategy to better treat intermittent and recurrent bone infections without the limitations of current short-lived drug release technologies. For this projected work, we will fabricate the environmentally responsive antibiotic coatings on the surface of metal plates used to stabilize bone fractures. These thin film coatings will contain potent antibiotics that target the most common bacteria that infect bone injuries. However, the films will also contain binder materials that are selectively broken down by free radicals generated through the body’s natural defenses during a bacterial infection. Therefore, the coatings will remain inert under normal conditions but will degrade and release their antibiotic payload only when an infection is detected. Since most conventional drug-loaded implants release their entire antibiotic dose within a few days of implantation in the body, these new responsive coatings are predicted to significantly prolong the delivery window and offer protection against bacterial re-infections. Responsive drug coatings that effectively eliminate bacteria without harming mammalian cells will first be established in lab testing. Finally, lead candidate coating formulations will be tested in an infected bone model in rats. These animal studies will confirm antimicrobial protection and improvements in bone healing as mediated by these responsive antibiotic coatings. This proposal represents an innovative departure from previous drug delivery technologies that rely on predetermined drug release rates and often do not match bacterial infection progression or recurrence events. Instead, this newly described delivery platform directly links localized, preventative antibiotic release to bacterial infection to prolong drug delivery profiles. Moreover, this system will employ simple film fabrication techniques for creating these responsive drug delivery systems, potentially enabling broad applicability across a host of antimicrobial indications. Ultimately, these efforts will establish the feasibility of responsive, preventative antibiotic delivery in orthopedic repair for the long-term goal of bringing this system into the clinic for both military and civilian bone infection treatment. This exciting work represents a promising advance for sustained release drug delivery technologies and has the potential to substantially improve patient care with these difficult to treat pathologies.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210075
Entities
People
- John D Martin
Organizations
- United States Army
- University of Cincinnati