The objective of this research is to determine the feasibility of developing an absorbable antimicrobial bone graft substitute for the treatment of osteomyelitis. Osteomyelitis occurs in an estimated 1-3% of all orthopedic surgeries with the incidence being even higher in spinal fusion and open fractures. Despite this rate of infection, there is currently no FDA approved implantable antibiotic loaded bone grafting material for the treatment and prevention of osteomyelitis. The research approach will employ a new absorbable biomaterial, known as TephaFLEX(tm) polymer, that offers a new set of properties for developing a suitable implantable drug delivery device for the treatment of osteomyelitis. In preliminary studies, it has been demonstrated that the TephaFLEX(tm) polymer can be loaded with a high percentage of a model antibiotic, and deliver this drug in vitro over a prolonged period that is potentially required for the treatment of osteomyelitis. The specific aims of this project are to: (1) Prepare antimicrobial drug release matrices from the TephaFLEX(tm) polymer and gentamicin that can be combined with existing bone graft materials, (2) Identify conditions to sterilize the TephaFLEX-gentimicin devices, (3) Identify suitable formulations of gentamicin loaded TephaFLEX(tm) bone graft substitutes and matrices that provide prolonged release of the antibiotic at therapeutic levels, (4) Confirm that gentamicin retains antibiotic activity after release and determine the Minimal Inhibitory Concentrations (MIC) of the sterilized bone graft substitutes and matrices against select target bacteria, (5) Confirm that the TephaFLEX(tm) devices lack cytotoxicity (i.e. grade <2) in an animal cell culture model for cell viability, and (6) Establish an animal model for infection that can be used to confirm the suitability of the TephaFLEX(tm) polymer for bone grafting, and also for Phase II in vivo studies of efficacy. In addition to developing a new product for the treatment of osteomyelitis, the research will also help to introduce a new absorbable medical biomaterial into the medical community that could be used in other drug delivery and medical device applications. Preliminary results using tetracycline and gentamycin release confirmed a linear release of antibiotic over a period typical for a course of antibiotic. Proposed experiments will employ bone matrix studies to demonstrate the dual utility of this polymeric composition
