Development and Pre-Clinical Testing of PEKK/Silicon Nitride Composite Craniomaxillofacial Implants

PEKK/氮化硅复合颅颌面植入物的开发和临床前测试

• 批准号: 10381823
• 负责人: Ryan Bock
• 金额: $ 30万
• 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: 2022-03-10 至 2024-03-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10381823
• 关键词: 3-Dimensional; 3D Print; Alloys; American; Anatomy; Anti-Bacterial Agents; Biocompatible Materials; Calvaria; Cell Culture Techniques; Cephalic; Ceramics; Characteristics; Clinical; Corrosion; Custom; Data; Defect; Deformity; Development; Devices; Disease; Effectiveness; Escherichia coli; Face; Failure; Filament; Fracture; Head; Health Care Costs; Image; Implant; In Vitro; Infection; Infection Control; Infection prevention; Injury; Joint repair; Link; Location; Malignant Neoplasms; Mandible; Maxilla; Mechanics; Medical Imaging; Medical center; Metals; Microbial Biofilms; Modeling; Modulus; Mus; Operative Surgical Procedures; Osseointegration; Outcome; Pain; Patient-Focused Outcomes; Patients; Performance; Polymers; Porosity; Powder dose form; Preclinical Testing; Printing; Process; Property; Prosthesis; Resistance; Resistance to infection; Services; Shapes; Specimen; Staphylococcus epidermidis; Stress; Surface; Surgeon; Technology; Testing; Time; Titanium; Trauma; Weight-Bearing state; Wistar Rats; antimicrobial; base; biomaterial compatibility; bone; bone repair; commercialization; cortical bone; cost; craniomaxillofacial; design; design-build-test; face bone structure; flexibility; healing; implant design; implant material; improved; in vitro testing; in vivo; in vivo evaluation; mechanical properties; novel; osteogenic; pathogen; physical property; polyetheretherketone; radiological imaging; reconstruction; response; septic; silicon nitride

PROJECT SUMMARY—Over 235,000 Americans undergo craniomaxillofacial (CMF) surgery annually, with implant failure rates averaging 5.5% in general and up to 37% and 52% in the orbital and temporal regions, respectively. Failures are attributed to prosthetic infections, poor osseointegration, corrosion, and fracture. Most can be linked to implant materials that underperform in terms of bioactivity, infection control, osseous integration, or mechanical stability. Thus, there continues to be a critical clinical need for medical imaging compatible 3DP biomaterials for craniomaxillofacial osteoplasty that can be personalized, promote integration, and prevent infection. SINTX Technologies, Inc. pioneered the use of silicon nitride (Si3N4) as a high-performance alternative to metal and polymer-based biomaterials for bone and joint repair. Si3N4 is a promising biomaterial for CMF defects because of its antibacterial activity, osseointegration, radiographic imaging, and durability, but the stiffness of Si3N4 engenders stress shielding and may be susceptible to subsidence and brittle fracture. In contrast, PEEK and PEKK are more flexible, radiotransparent biomaterials, but these polymers lack antimicrobial and osseointegrative properties. To overcome these limitations, SINTX proposes to combine its bioactive Si3N4 with PEKK to form a 3D-printable composite that will be radiolucent, possess an elastic modulus similar to cortical bone, and simultaneously provide improved antimicrobial and osteointegration properties. The purpose of this application is to design, build, and test 3DP PEKK/Si3N4 composite for non-load-bearing CMF implants that satisfy material requirements and enhance infection resistance and osseous integration. Aim 1. Design, produce, and characterize porous 3DP PEKK/Si3N4 implants for non-load-bearing CMF applications. Milestones: 1) Prepare PEKK/Si3N4 composite filaments based on a range of PEKK/Si3N4 volume ratios; 2) Design an appropriate CMF implant based on the amount and type of included porosity; 3) Validate the 3D printability of the various PEKK/Si3N4 composites; and 4) Assess the physical and mechanical properties of the 3DP CMF composite designs. Aim 2. Complete in vitro antibacterial and osteoconductivity testing of the preferred 3DP PEKK/Si3N4 implant from Aim 1. Milestones: Demonstrate that test components from the preferred 3DP PEKK/Si3N4 implant 1) Achieve a ≥ 1.5-log10 reduction in Staphylococcus epidermidis (S. epidermidis) and Escherichia coli (E. coli); and 2) demonstrate an ability to significantly upregulate osteoblastic activity. Aim 3. Test the in vivo antimicrobial effectiveness and overall healing of the 3DP PEKK/Si3N4 implant compared to PEEK. Milestones: 1) Prepare and characterize identical 3DP partially porous PEKK/Si3N4 and PEEK implants; and 2) Complete a 28-day in vivo time-course study of these implants under aseptic and septic conditions in Wistar rats. Impact – This proof-of-concept project is expected to provide strong rationale and preliminary data to support further study and commercialization of a 3D-printable PEKK/Si3N4 composite for CMF implants, which could substantially reduce implant failures due to infection and/or poor bone integration.

项目摘要-每年有超过235,000名美国人接受颅颌面(CMF)手术， 植入物失败率总体平均为5.5%，眼眶和颞区分别高达37%和52%， 分别进行了分析。失败归因于假体感染、骨整合不良、腐蚀和骨折。多数 可以与生物活性、感染控制、骨整合、 或机械稳定性。因此，临床上仍然迫切需要兼容的医学成像技术。 3DP生物材料用于颅颌面骨成形术，可个性化，促进整合，以及 预防感染。SINTX Technologies，Inc.率先使用氮化硅(Si3N4)作为高性能 可替代金属和聚合物为基础的生物材料用于骨和关节修复。氮化硅是一种很有前途的生物材料 对于CMF缺陷，因为它的抗菌活性、骨整合、放射成像和耐用性，但 Si3N4的硬度产生应力屏蔽，容易下沉和脆性断裂。在……里面 相比之下，PEEK和PEKK是更具弹性、辐射透明的生物材料，但这些聚合物缺乏抗菌剂 和骨整合性能。为了克服这些限制，SINTX建议将其生物活性Si3N4 使用PEKK形成一种3D可打印的复合材料，该复合材料将是放射透明的，具有类似于皮质的弹性模量 同时提供更好的抗菌剂和骨结合性能。这样做的目的是 应用是设计、制造和测试3DP PEKK/Si3N4复合材料，用于非承重CMF植入物 满足材料要求，增强抗感染能力和骨结合能力。目标1.设计、 生产并表征用于非承重CMF应用的多孔3DP PEKK/Si3N4植入物。 里程碑：1)根据一定范围的PEKK/Si3N4体积比制备PEKK/Si3N4复合丝； 根据包含孔洞的数量和类型设计合适的CMF种植体；3)验证3D 各种PEKK/Si3N4复合材料的印刷适性；以及4)评估PEKK/Si3N4复合材料的物理和机械性能 3DP CMF复合材料设计。目的2.完成体外抗菌和骨传导性测试 首选来自Aim 1的3DP PEKK/Si3N4植入物。里程碑：展示来自 优选的3DP PEKK/Si3N4植入物1)使表皮葡萄球菌(S)的≥降低1.5-log10。 以及2)显示出显著上调成骨细胞的能力 活动。目的3.检测3DP-PEKK/Si3N4的体内抑菌效果和整体愈合情况 植入物与偷看相比较。里程碑：1)制备和表征相同的3DP部分多孔PEKK/Si3N4 和PEEK植入物；以及2)完成这些植入物在无菌和 Wistar大鼠的败血症情况。影响--这一概念验证项目预计将提供强有力的理由 以及支持可3D打印的PEKK/Si3N4复合材料的进一步研究和商业化的初步数据 CMF种植体，可大大减少因感染和/或骨结合不良而导致的种植体失败。