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

涂有角锥蛋白的椎弓根螺钉可解决手术部位感染。

• 批准号: 10602633
• 负责人: Glenn Brunner
• 金额: $ 25.85万
• 依托单位: N8 MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-02 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10602633
• 关键词: Anti-Infective Agents; Antibiotic Prophylaxis; Antibiotics; Biochemistry; Body Weight; Bone Screws; Businesses; California; Candida albicans; Cells; Chemistry; Clinical; Communities; Complete Blood Count; Deterioration; Development; Device or Instrument Development; Dose; Effectiveness; Excision; Extracellular Matrix; Face; Failure; Formulation; Frequencies; Functional disorder; Generations; Genus staphylococcus; Gram-Negative Bacteria; Harvest; Health; Healthcare Systems; High Pressure Liquid Chromatography; Immune; Implant; Implantation procedure; In Vitro; Infection; International; Intervention; Leadership; Length of Stay; Licensing; Local Anti-Infective Agents; Marketing; Measures; Mechanical Stress; Medical; Medical Device; Medical Technology; Medicine; Metals; Microbial Biofilms; Microscopic; Modeling; Modification; Monitor; Morbidity - disease rate; Operative Surgical Procedures; Organ; Oryctolagus cuniculus; Patients; Penetration; Pharmaceutical Preparations; Phase; Polymers; Population; Postoperative Period; Principal Investigator; Process; Production; Property; Pseudomonas aeruginosa; Quality of life; Reporting; Resistance; Risk; Safety; Sales; Second Look Surgery; Small Business Innovation Research Grant; Spinal; Spine surgery; Staphylococcus aureus; Surface; Surgeon; Surgical Models; Surgical Wound Infection; Tissue Sample; Tissues; Titanium; Universities; Validation; Vertebral column; amphiphilicity; antimicrobial; antimicrobial peptide; biomaterial compatibility; bone; design; experience; flexibility; functional outcomes; fungus; implantation; improved; in vivo; in vivo evaluation; infection rate; large scale production; lumbar vertebra bone structure; medical implant; metallicity; methicillin resistant Staphylococcus aureus; microbial colonization; microorganism; mortality; mortality risk; novel; pathogen; phase 1 study; polycaprolactone; pre-clinical; prevent; professor; resistant strain; spine bone structure; success

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.

项目总结 手术部位感染(SSI)是植入物手术的主要并发症之一，尤其是在脊柱手术中。 SSI会导致不良的健康和功能结果。抗菌涂料已经被探索为 一种防止椎弓根螺钉表面微生物定植的方法。然而，目前的战略是产生 抗菌涂层不具有广谱抗菌活性；事实上，它们会产生细菌 以及对真菌的耐药性。N8医疗公司提出一种具有新型抗感染涂层的椎弓根螺钉，其基础是 角蛋白(CSA)，它模拟抗菌肽(AMP)，能够清除细菌和 真菌种群(包括耐药菌株)和防止生物膜的形成而不产生 抵抗。该涂层将被设计为聚己内酯(PCL)基材，其中含有环孢素A，一种合成的 模拟自然产生的AMPS的化合物，显示出剂量依赖的抗感染活性 阳性和革兰氏阴性细菌和真菌。N8医疗的技术将颠覆医疗设备 通过提出一种对广谱病原体有效的解决方案， 包括耐药菌株，防止生物被膜的形成，并且没有已知的抗药性池。通过减少 脊柱手术期间的SSI率，N8 Medical将1)减轻医疗系统的负担，相关 通过更长的住院时间和翻修手术；2)减少种植失败的频率；以及3)改善 脊柱手术患者的生活质量。由于高度可扩展，N8 Medical的涂层平台 有可能在广泛的临床干预中预防手术部位感染并改善生活质量 需要任何一种留置医疗器械的病人。N8医疗公司将把其涂层椎弓根螺钉出售给 通过直接销售和间接销售相结合的方式建立医疗保健体系。该平台的灵活性将允许 从长远来看，该公司将考虑基于许可的商业模式。该SBIR第一阶段项目旨在 确定了N8 Medical的CSA涂层用于钛椎弓根螺钉的技术可行性。 用于脊柱外科手术。为了实现这一点，N8医疗公司将评估涂有环孢素A负载的椎弓根螺钉 不同浓度环孢素A和不同比例环孢素A的体外抗耐药效果 葡萄球菌菌株。此外，CsA的释放量将用高效液相色谱法测定，涂层的耐久性将 使用腰椎模型进行评估。最后，涂层的有效性和安全性将在体内进行测试 在兔脊柱手术模型中。第一阶段项目的成功将为第二阶段的活动奠定基础 其中N8医疗将优化涂料配方和生产工艺，并进一步调查 涂层的生物相容性、有效性和安全性。