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200万美国人的骨折住院， 更多的人接受了裂缝减少和固定的门诊手术。一些伤害可以治疗 闭合的还原和夹板或铸造以使骨骼固定在愈合过程中。但是，在某些站点，更多 一半的断裂需要开放式减少和内固定。尽管植入材料的进步，但植入物 - 相关感染仍然是一个挑战。根据骨折的位置，受伤的特征 （例如，开放式与闭合断裂）和患者的特征（例如，存在糖尿病或其他 合并症），在1％至30％之间的固定位点受到设备相关感染的损害。为了 例如，需要内固定的下肢分数与阻碍的高感染率有关 骨骼愈合，增加长期残疾的风险，并增加患者护理的成本和复杂性。 需要进一步的固定设备材料来减少与设备相关感染的发生率 并改善患者预后。在此阶段I STTR中，Sintx Technologies试图证明 新型抗菌材料的概念，可用于产生广泛的内固定范围 断裂修复的设备。创伤板是创伤中使用最广泛的内固定装置 申请。盘子通常由金属，模制碳纤维增强（CFR）聚醚醚制成 （窥视）复合材料或CFR-聚酮酮（CFR-Pekk）。不幸的是，所有这些设备 材料容易感染。 SINTX率先使用氮化硅（Si3n4）instars 抗菌活性，并在临床使用方面达到了极好的抗感染概况（即，只有0.006％ 尽管Si3n4具有出色的抗菌特性，但它是 容易受到脆性骨折的影响，因此不适合稳定裂缝。在这个阶段，我sttr，sintx和 它的合作者建议使用专有过程将微观Si3n4粉末嵌入 CFR-Pekk并评估了这种新颖材料作为固定装置的抗菌材料的性能。 创伤板将作为概念证明的原型 创伤板用于进一步开发和商业化，b）证明了材料的潜力 用于在其他必须承受体内载荷，促进成像和电阻感染的固定装置中使用。 AIM 1。设计符合或超过静态要求或超出静态要求的α-SI3N4 -CFR-PEKK创伤板 疲劳弯曲强度。 AIM 1里程碑：设计和开发一个涂有SI3N4涂层的CFR- PEKK创伤板 按照固定至少90％的静态和疲劳弯曲强度 ASTM F382，D7264，D790-10。 AIM 2。将抗菌活性和生物相容性作为功能表征 α-SI3N4百分比。 AIM 2里程碑：A> 2降低细菌定殖的原木，同时保留成骨细胞 增殖/成熟。