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

项目摘要 手术部位感染（SSI）是植入手术的主要并发症之一，尤其是在脊柱手术中， SSI导致不利的健康和功能结果。抗微生物涂层已经被探索为 一种防止微生物在椎弓根螺钉表面定植的方法。然而，目前的战略， 抗菌涂层不显示广谱抗菌活性;事实上，它们可以产生细菌， 和真菌抗性。N8 Medical提出了一种具有新型抗感染涂层的椎弓根螺钉， 模拟抗菌肽（AMP）的角鲨烷配基（CSA）能够根除细菌和 真菌种群（包括耐药菌株），并防止生物膜的形成而不产生 阻力涂层将被设计为载有CSA的聚己内酯（PCL）基材，CSA是一种合成的 模拟天然存在的AMP的化合物，其显示针对革兰氏菌的剂量依赖性抗感染活性， 阳性和革兰氏阴性细菌和真菌。N8 Medical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， 包括抗性菌株，防止生物膜的形成，并且没有已知的抗性库。通过减少 脊柱手术期间的SSI率，N8医疗将1）减少医疗保健系统的负担， 延长住院时间和翻修手术; 2）降低植入物失效的频率; 3）改善 脊柱手术患者的生活质量（QoL）。N8 Medical的涂层平台具有高度可扩展性， 有可能在广泛的临床干预中预防手术部位感染并改善QoL 需要任何类型留置医疗器械的患者。N8 Medical将把其涂层椎弓根螺钉出售给 通过直接和间接销售相结合的医疗保健系统。平台的灵活性将允许 从长远来看，公司应该考虑以许可为基础的商业模式。SBIR第一阶段项目旨在 确定N8 medical的CSA涂层用于钛椎弓根螺钉的技术可行性， 用于脊柱手术。为了实现这一点，N8 Medical将评价涂有CSA负载的椎弓根螺钉 PCL（不同浓度的CSA和不同百分比的PCL）的体外抗耐药的功效， 葡萄球菌菌株。此外，CSA的释放将通过HPLC测量，并且涂层耐久性将 使用腰椎模型进行评估。最后，将对涂层的有效性和安全性进行体内试验 在兔子脊柱手术模型中。第一阶段项目的成功将为第二阶段活动奠定基础 N8 Medical将优化涂层配方和生产工艺，并进一步研究 涂层的生物相容性、有效性和安全性。

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.