Development and Pre-Clinical Testing of Antimicrobial PEKK/Silicon Nitride Trauma Plates with Carbon Fiber Reinforcement

项目摘要-每年有200多万美国人因骨折住院， 更多的人接受门诊手术进行骨折复位和固定。有些伤可以用来治疗 闭合复位和夹板固定或铸型，在愈合过程中固定骨骼。然而，在一些网站，更多的 超过一半的骨折需要切开复位和内固定。尽管植入材料取得了进步，但植入物- 相关感染仍然是一项挑战。根据骨折的位置、损伤的特征 (例如，开放性骨折与闭合性骨折)以及患者的特征(例如，是否存在糖尿病或其他 合并症)，1%到30%的固定部位受到设备相关感染的影响。为 例如，需要内固定的下肢骨折与高感染率有关，这阻碍了 骨愈合，增加了长期残疾的风险，并增加了患者护理的成本和复杂性。 需要在固定装置材料方面取得进一步的进展，以减少装置相关感染的发生率 并改善患者的预后。在此第一阶段STTR中，SINTX Technologies寻求证明- 一种可用于生产广泛内固定的新型抗菌材料的概念 用于骨折修复的设备。创伤接骨板是目前应用最广泛的创伤内固定器械 申请。板材通常由金属模压碳纤维增强(CFR)聚醚醚酮制成。 (PEEK)复合材料或CFR-聚醚酮酮(CFR-PEKK)。不幸的是，由所有这些材料制成的设备 材料容易受到感染。SINTX率先使用了氮化硅(Si3N4)植入物，它具有固有的 抗菌活性，并在临床应用中取得了良好的抗感染效果(即只有0.006 植入物与感染有关)。尽管Si3N4具有优异的抗菌性能，但它是 易发生脆性断裂，因此不适合稳定裂缝。在此第一阶段中，STTR、SINTX和 其合作者建议使用一种专利工艺将微小的Si3N4粉末嵌入到 CFR-PEKK，并评价这种新型材料作为固定装置抗菌材料的性能。 创伤钢板将作为概念验证的原型，目标是a)推进Si3N4-CFR-PEKK 用于进一步开发和商业化的创伤钢板，以及b)展示该材料的潜力 用于其他必须能承受活体负荷、便于成像和抵抗感染的固定装置。 目的1.设计一种满足或超过静力学要求的α-Si3N4-CFR-PEKK创伤接骨板 疲劳弯曲强度。目标1里程碑：设计和开发一种涂有Si3N4的CFR-PEKK创伤钢板 保持未涂层创伤接骨板至少90%的静态和疲劳弯曲强度 ASTM F382、D7264、D790-10。目的2.表征抗菌活性和生物相容性 α-Si3N4百分比。目标2里程碑：A&gt；2在保留成骨细胞的同时减少细菌定植 增殖/成熟。

PROJECT SUMMARY—More than 2 million Americans are hospitalized each year with bone fractures, and many more undergo outpatient procedures for fracture reduction and fixation. Some injuries can be treated with closed reduction and splinting or casting to immobilize the bone during healing. However, at some sites, more than half of fractures require open reduction and internal fixation. Despite advances in implant materials, implant- associated infections remain a challenge. Depending on the location of the fracture, characteristics of the injury (e.g., open vs. closed fracture), and characteristics of the patient (e.g., presence of diabetes or other comorbidities), between 1% and 30% of fixation sites are compromised by device-associated infections. For example, lower extremity fractures requiring internal fixation are associated with high infection rates that impede bone healing, increase the risk of long-term disability, and increase the cost and complexity of patient care. Further advances in fixation device materials are needed to reduce the incidence of device-associated infections and improve patient outcomes. In this Phase I STTR, SINTX Technologies seeks to demonstrate proof-of- concept for a novel antimicrobial material that could be used to produce a broad range of internal fixation devices for fracture repair. Trauma plates are the most widely used internal fixation devices in trauma applications. Plates are typically crafted from metal, molded carbon fiber reinforced (CFR) polyetheretherketone (PEEK) composites, or CFR-polyetherketoneketone (CFR-PEKK). Unfortunately, devices made from all of these materials are prone to infection. SINTX pioneered the use of silicon nitride (Si3N4) implants that have inherent antimicrobial activity and have achieved an excellent anti-infective profile in clinical use (i.e., only 0.006% of implants have been associated with infection). Although Si3N4 has excellent antimicrobial properties, it is susceptible to brittle fracture and therefore not suitable for stabilizing fractures. In this Phase I STTR, SINTX and its collaborators propose to use a proprietary process to embed microscopic Si3N4 powder into the surface of CFR-PEKK and evaluate this novel material’s performance as an antimicrobial material for fixation devices. Trauma plates will serve as a prototype for proof-of-concept, with the goals of a) advancing a Si3N4-CFR-PEKK trauma plate for further development and commercialization and b) demonstrating the potential for the material to be used in other fixation devices that must withstand in vivo loading, facilitate imaging, and resist infection. Aim 1. Design an α-Si3N4 -CFR-PEKK trauma plate that meets or exceeds requirements for static and fatigue bending strength. Aim 1 Milestone: Design and develop a Si3N4-coated CFR- PEKK trauma plate that preserves at least 90% of static and fatigue bending strength of uncoated trauma plates in accordance with ASTM F382, D7264, D790-10. Aim 2. Characterize antibacterial activity and biocompatibility as a function of α-Si3N4 percentage. Aim 2 Milestone: A > 2 log reduction in bacterial colonization while retaining osteoblastic proliferation/maturation.