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

项目总结-每年有超过235，000名美国人接受颅颌面（CMF）手术， 植入失败率平均为5.5%，眼眶和颞区分别高达37%和52%， 分别失败归因于假体感染、骨结合不良、腐蚀和断裂。最 可能与在生物活性、感染控制、骨整合方面表现不佳的植入材料有关， 或机械稳定性。因此，仍然存在对医学成像兼容的关键临床需求。 用于颅颌面骨成形术的3DP生物材料，可以个性化，促进整合， 防止感染。SINTX Technologies，Inc.率先使用氮化硅（Si 3 N4）作为高性能 用于骨和关节修复的金属和聚合物基生物材料的替代品。氮化硅是一种很有前途的生物材料 由于其抗菌活性、骨整合、放射成像和耐久性， Si 3 N4的硬度产生应力屏蔽，并且可能易于下沉和脆性断裂。在 相比之下，PEEK和PEKK是更柔韧的、辐射透明的生物材料，但这些聚合物缺乏抗菌性， 和骨整合特性。为了克服这些局限性，SINTX提出将其生物活性Si 3 N4联合收割机 与PEKK形成一种3D可打印的复合材料，该复合材料将是放射性的，具有与皮质骨相似的弹性模量， 骨，并同时提供改善的抗微生物和骨整合性质。这样做的目的 应用程序是设计，构建和测试用于非承重CMF植入物的3DP PEKK/Si 3 N4复合材料， 满足材料要求，增强抗感染能力和骨整合能力。目标1.设计、 生产和表征用于非承重CMF应用的多孔3DP PEKK/Si 3 N4植入物。 步骤：1）基于一定范围的PEKK/Si 3 N4体积比制备PEKK/Si 3 N4复合长丝; 2） 根据所含孔隙的数量和类型设计适当的CMF植入物; 3）对3D 各种PEKK/Si 3 N4复合材料的可印刷性;以及4）评估所述复合材料的物理和机械性能。 3DP CMF复合材料设计。目标2.完成体外抗菌和骨传导性测试， 优选来自Aim 1的3DP PEKK/Si 3 N4植入物。Military：演示来自 优选的3DP PEKK/Si 3 N4植入物1）实现表皮葡萄球菌（S. epidermidis）和大肠杆菌（E.大肠杆菌）;和2）证明能够显著上调成骨细胞 活动目标3。测试3DP PEKK/Si 3 N4的体内抗菌有效性和整体愈合 与PEEK相比。步骤：1）制备并表征相同的3DP部分多孔PEKK/Si 3 N4 和PEEK植入物;和2）在无菌和无菌条件下完成这些植入物的28天体内时程研究， Wistar大鼠的败血症条件。影响-该概念验证项目预计将提供强有力的理由 和初步数据，以支持3D可打印的PEKK/Si 3 N4复合材料的进一步研究和商业化， CMF植入物，可显著减少因感染和/或骨整合不良导致的植入物失效。

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.