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

碳纤维增强抗菌 PEKK/氮化硅创伤板的开发和临床前测试

• 批准号: 10600180
• 负责人: Ryan Bock
• 金额: $ 27.57万
• 依托单位: SINTX TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-22 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10600180
• 关键词: Advanced Development; American; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Area; Bacterial Infections; Biocompatible Materials; Biomechanics; Cells; Characteristics; Clinical; Closed Fractures; Development; Devices; Diabetes Mellitus; Escherichia coli; Exhibits; Fatigue; Formulation; Foundations; Fracture; Future; Goals; Human; Image; Immobilization; Impaired healing; Implant; Incidence; Infection; Infection prevention; Injury; Internal Fixators; Location; Lower Extremity Fracture; Metals; Microscopic; Molds; Operative Surgical Procedures; Osteoblasts; Outpatients; Patient Care; Patient-Focused Outcomes; Patients; Performance; Phase; Powder dose form; Preclinical Testing; Procedures; Process; Property; Psychological reinforcement; Radiology Specialty; Research; Risk; Site; Small Business Technology Transfer Research; Source; Splint Device; Staphylococcus aureus; Surface; Surgeon; Technology; Time; Trauma; United States National Institutes of Health; antimicrobial; biomaterial compatibility; bone; bone fracture repair; bone healing; bone repair; carbon fiber; commercialization; comorbidity; cost; design; disability; ductile; healing; implant associated infection; implant material; implantable device; improved; in vivo; in vivo Model; infection rate; infection risk; novel; osteoblast proliferation; polyetheretherketone; pre-clinical; preservation; prevent; prototype; research clinical testing; sample fixation; silicon nitride

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.

项目摘要——每年有超过 200 万美国人因骨折住院， 更多的人接受骨折复位和固定的门诊手术，一些损伤可以通过以下方法治疗。 闭合复位和夹板或铸造以在愈合过程中固定骨骼，但在某些部位需要更多。 尽管植入材料有所进步，但超过一半的骨折需要切开复位和内固定。 相关感染仍然是一个挑战，具体取决于骨折的位置、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，是否患有糖尿病或其他疾病） 并发症），1% 到 30% 的固定部位受到设备相关感染的影响。 例如，需要内固定的下肢骨折与高感染率相关，这阻碍了 骨愈合，增加长期残疾的风险，并增加患者护理的成本和复杂性。 需要进一步改进固定装置材料，以减少装置相关感染的发生率 并改善患者的治疗结果。在第一阶段 STTR 中，SINTX Technologies 力求证明- 可用于生产各种内固定物的新型抗菌材料的概念 骨折修复装置是创伤中使用最广泛的内固定装置。 板通常由金属模制碳纤维增强 (CFR) 聚醚醚酮制成。 (PEEK) 复合材料或 CFR-聚醚酮酮 (CFR-PEKK) 不幸的是，这些设备都是由所有这些材料制成的。 SINTX 率先使用具有固有特性的氮化硅 (Si3N4) 植入物。 抗菌活性，并在临床使用中取得了优异的抗感染特性（即仅占 0.006%） 尽管 Si3N4 具有优异的抗菌性能，但它与感染有关。 容易发生脆性断裂，因此不适合稳定断裂 在第一阶段 STTR、SINTX 和 其合作者建议使用专有工艺将微观 Si3N4 粉末嵌入到表面 CFR-PEKK 并评估这种新型材料作为固定装置抗菌材料的性能。 创伤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板 b) 展示该材料的潜力 用于其他必须承受体内负载、便于成像和抵抗感染的固定装置。 目标 1. 设计满足或超过静态和静态要求的 α-Si3N4 -CFR-PEKK 创伤板 目标 1 里程碑：设计并开发出一种具有 Si3N4 涂层的 CFR-PEKK 创伤板，可抗疲劳。 根据以下标准，保留未涂层创伤板至少 90% 的静态和疲劳弯曲强度 ASTM F382、D7264、D790-10。目标 2. 将抗菌活性和生物相容性表征为函数。 目标 2 里程碑：细菌定植减少 > 2 个对数，同时保留成骨细胞。 增殖/成熟。