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200多万美国人因骨折住院， 更多的人接受门诊骨折复位和固定手术。有些伤可以用 闭合复位和夹板或石膏以在愈合期间固定骨。然而，在一些地方， 一半以上的骨折需要切开复位内固定。尽管植入物材料有了进步，但植入物- 相关感染仍然是一个挑战。根据骨折的位置，损伤的特征 (e.g.,开放性骨折与闭合性骨折），以及患者的特征（例如，存在糖尿病或其他 合并症），1%至30%的固定部位受到器械相关感染的影响。为 例如，需要内固定的下肢骨折与高感染率相关， 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器械材料以降低器械相关感染的发生率 和改善患者结果。在第一阶段STTR中，SINTX技术公司试图证明 一种新型抗菌材料的概念，可用于生产广泛的内固定 用于骨折修复的器械。创伤钢板是创伤中应用最广泛的内固定器械 应用.接骨板通常由金属、模制碳纤维增强（CFR）聚醚醚酮制成 聚醚醚酮（PEEK）复合材料或CFR-聚醚酮酮（CFR-PEKK）。不幸的是，由所有这些制成的设备 材料易于感染。SINTX率先使用氮化硅（Si 3 N4）植入物， 抗微生物活性并在临床应用中获得了优异的抗感染特性（即，只有0.006%的 植入物与感染有关）。虽然Si 3 N4具有优异的抗微生物性能，但它 易发生脆性断裂，因此不适于稳定断裂。在第一阶段STTR中，SINTX和 其合作者提出使用一种专有工艺将微观Si 3 N4粉末嵌入到 CFR-PEKK，并评价这种新型材料作为固定器械抗菌材料的性能。 创伤接骨板将作为概念验证的原型，目标是a）推进Si 3 N4-CFR-PEKK 用于进一步开发和商业化的创伤板和B）证明该材料的潜力 用于必须承受体内载荷、便于成像和抗感染的其他固定器械。 目标1.设计一种α-Si 3 N4-CFR-PEKK创伤接骨板，满足或超过静态和 疲劳弯曲强度目标1里程碑：设计和开发一种Si 3 N4涂层CFR- PEKK创伤接骨板， 根据以下要求，保持无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。目标2.表征抗菌活性和生物相容性作为功能 α-Si_3N_4含量目标2里程碑：细菌定植减少> 2 log，同时保留成骨细胞 增殖/成熟。