Ceragenin-coated pedicle screws to tackle surgical-site infections.

PROJECT SUMMARY Surgical Site Infection (SSI) is one of the major complications of implant surgery, especially in spinal surgery, where SSI leads to unfavorable health and functional outcomes. Antimicrobial coatings have been explored as a way to prevent microbial colonization on the surface of pedicle screws. However, current strategies to generate antimicrobial coatings do not show broad-spectrum antimicrobial activity; in fact, they can engender bacterial and fungal resistance. N8 Medical proposes a pedicle screw with a novel anti-infective coating based on ceragenins (CSAs), which mimic antimicrobial peptides (AMPs) and are able to eradicate both bacterial and fungal populations (including resistant strains) and to prevent the formation of biofilms without engendering resistance. The coating will be designed as a polycaprolactone (PCL) substrate loaded with CSA, a synthetic compound mimicking naturally occurring AMPs that shows dose-dependent anti-infective activity against Gram- positive and Gram-negative bacteria and fungi. N8 Medical’s technology will disrupt the medical devices antimicrobial coating market by proposing a solution that has efficacy against a broad-spectrum of pathogens, including resistant strains, prevents the formation of biofilms, and has no known resistance pools. By reducing the SSI rate during spinal surgery, N8 Medical will 1) reduce the burden on the healthcare system, associated with longer hospital stays and revision surgeries; 2) reduce the frequency of implant failure; and 3) improve the quality of life (QoL) of patients undergoing spinal surgery. Being highly scalable, N8 Medical’s coating platform has the potential to prevent surgical site infections in a wide range of clinical interventions and improve the QoL of patients in need of any kind of indwelling medical device. N8 Medical will sell its coated pedicle screws to the healthcare system through a combination of direct and indirect sales. The flexibility of the platform will allow the company to consider a licensing-based business model in the long term. This SBIR Phase I project aims at establishing the technical feasibility of N8 medical’s CSA-based coating for titanium pedicle screws, which are used in spinal surgery. To achieve this, N8 Medical will evaluate the pedicle screws coated with CSA-loaded PCL (different concentrations of CSA and varying percentages of PCL) for their in vitro efficacy against resistant Staphylococcus strains. In addition, the release of CSA will be measured by HPLC and the coating durability will be evaluated using a lumbar vertebra model. Finally, the efficacy and safety of the coating will be tested in vivo in a rabbit spinal surgery model. The success of the Phase I project will lay the ground for Phase II activities where N8 Medical will optimize the coating formulation and the production process, and further investigate coating biocompatibility, efficacy, and safety.