SBIR-STTR Award

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.

Public Health Relevance Statement:
PROJECT NARRATIVE Surgical Site Infection (SSI) is one of the major complications of spinal surgery, where SSI leads to unfavorable health and functional outcomes. Current strategies to generate antimicrobial coatings to prevent microbial colonization on the surface of implanted medical devices, such as pedicle screws, do not show broad-spectrum antimicrobial activity. N8 Medical proposes a novel coated pedicle screw based on ceragenins (CSAs) able to eradicate both bacterial and fungal populations (including resistant strains) and to prevent the formation of biofilms without engendering resistance.

Project Terms:
Anti-Infective Drugs; Anti-Infectives; Anti-infective Preparation; AntiInfective Drugs; AntiInfectives; Antiinfective Agents; communicable disease control agent; Anti-Infective Agents; Antiseptics; Local Antiinfective Agents; Topical Anti-Infective Agents; Topical Antiinfective Agents; Local Anti-Infective Agents; Antibiotic Agents; Antibiotic Drugs; Miscellaneous Antibiotic; Antibiotics; Biochemistry; Biological Chemistry; Body Weight; bone; Bone Screws; California; Candida albicans; C albicans; C. albicans; C.albicans; Cells; Cell Body; Chemistry; High Pressure Liquid Chromatography; HPLC; High Performance Liquid Chromatography; High Speed Liquid Chromatography; Communities; Complete Blood Count; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Extracellular Matrix; Cell-Extracellular Matrix; ECM; Face; faces; facial; fungus; Gram-Negative Bacteria; Health; Healthcare Systems; Health Care Systems; Implantation procedure; implant placement; implant procedure; In Vitro; Infection; Leadership; Length of Stay; Number of Days in Hospital; hospital days; hospital length of stay; hospital stay; lumbar vertebra bone structure; Lumbar Vertebrae; Marketing; Medical Device; Medicine; Metals; Morbidity - disease rate; Morbidity; mortality; Patients; Polymers; polymer; polymeric; Postoperative Period; Post-Operative; Postoperative; Production; Pseudomonas aeruginosa; P aeruginosa; P. aeruginosa; Pseudomonas pyocyanea; Quality of life; QOL; Oryctolagus cuniculus; Domestic Rabbit; Rabbits; Rabbits Mammals; Risk; Safety; Sales; Vertebral column; Spinal Column; Spine; backbone; Genus staphylococcus; Staphylococcus; Staphylococcus aureus; S aureus; S. aureus; Staph aureus; Mechanical Stress; Surgical Wound Infection; surgical site infection; Medical Technology; Tissues; Body Tissues; Titanium; Ti element; Universities; Generations; Measures; Microbial Biofilms; biofilm; Businesses; polycaprolactone; Organ; improved; Surface; Clinical; Microscopic; Penetration; Phase; Medical; Failure; Licensing; Dysfunction; Physiopathology; pathophysiology; Functional disorder; Antibiotic Premedication; Antibiotic Prophylaxis; Frequencies; Immune; Immunes; microorganism; Spinal; Operative Surgical Procedures; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; spine bone structure; Vertebrae; Vertebral; Surgeon; amphiphilicity; biomaterial compatibility; biocompatibility; experience; success; microbial colonization; professor; novel; Reporting; Excision; Abscission; Extirpation; Removal; Surgical Removal; resection; Deterioration; Modeling; Property; Intervention; Intervention Strategies; interventional strategy; Surgical Models; Second Look Surgery; Second Look; Surgical Revision; MRSA; Methicillin Resistant S Aureus; Methicillin Resistant S. Aureus; methicillin-resistant S. aureus; methicillin resistant Staphylococcus aureus; Effectiveness; Tissue Sample; preventing; prevent; Dose; Device or Instrument Development; device development; instrument development; Harvest; International; in vivo; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Validation; validations; Monitor; Principal Investigator; Process; Modification; Development; developmental; pre-clinical; preclinical; antimicrobial peptide; anti-microbial peptide; medical implant; designing; design; functional outcomes; pathogen; Population; resistant; Resistance; anti-microbial; antimicrobial; Implant; implantation; resistance strain; resistant strain; full scale manufacturing; large scale manufacturing; mass production; large scale production; flexible; flexibility; Phase I Study; phase 1 study; metallicity; Formulation; Spinal surgery; Spine surgery; in vivo testing; in vivo evaluation; death risk; mortality risk; rate of infection; infection rate