3D Printed Silicon Nitride Porous PEEK Composite Spinal Cages for Anti-Infection

项目总结-当颈部和背部疼痛变得难以治愈时，脊柱融合术是金标准 治疗然而，高达12%的这些融合由于感染而失败，导致大量的个人和经济损失。 成本在大多数情况下，这些感染与用于稳定融合的硬件有关。传统上 模制或机加工的聚醚醚酮（PEEK）保持架由于PEEK的 强度、与骨相当的弹性模量、生物相容性和射线可透性。传统的PEEK 融合器和普通替代物容易发生脊柱感染。氮化硅（Si 3 N4）间隔物已经被用于 其它具有优异抗微生物性能历史的脊柱应用（即，只有0.006%的植入物 与感染相关），并且与其他材料相比，它们提供了更好的上级骨整合。 不幸的是，Si 3 N4对于稳定脊柱融合不是理想的，因为该材料可能易受损伤。 沉陷和脆性断裂。在第一阶段STTR中，SINTX技术公司与德雷克塞尔大学合作， 和托马斯杰斐逊大学，将结合联合收割机的抗菌和骨整合性能的氮化硅与 利用PEEK的强度和弹性开发新型3D打印抗菌颈椎融合器。发展和 3DP Si 3 N4-PEEK颈椎椎间融合器的商业化将解决 抗微生物脊柱融合稳定器，其促进骨整合，承受体内负荷， 显像目标1。设计符合ASTM静态载荷要求的3DP Si 3 N4-PEEK颈椎融合器 F2077里程碑：证明3DP Si 3 N4-PEEK多孔的静态压缩、剪切和扭转强度 符合或超过ASTM F2077制定的颈椎融合器指南，并进行基准测试 对于文献中的许多保持架制造商。目标二。确定抗菌活性和成骨细胞 增殖/成熟作为Si 3 N4百分比的函数。里程碑：A >1.5对数减少细菌 定植，同时保持成骨细胞增殖/成熟。影响-预计该项目将 证明了创建同时保留上级放射学和 3DP PEEK生物材料的生物力学质量，同时保持骨整合和抗菌性 Si 3 N4的质量。II期STTR或SBIR将使3DP Si 3 N4-PEEK颈椎融合器实现IDE 研究，包括疲劳性能、抗沉陷性和临床前性能的评估， 全尺寸严格供电的体内模型。合理设计的抗菌脊柱融合器，可靠减少 感染是至关重要的，特别是考虑到融合失败的个人和财务成本以及越来越多的 由于我们的人口老龄化，美国的脊柱融合数量。进展至II期的里程碑- 交付3DP Si 3 N4-PEEK颈椎融合器，（1）满足ASTM F2077的静态载荷要求，（2） 符合骨整合的最低性能阈值，以及（3）符合最低性能阈值 用于抗菌活性。该方法中包含了量化目标。

PROJECT SUMMARY—When neck and back pain becomes intractable, spinal fusion is the gold-standard treatment. However, up to 12% of these fusions fail due to infection, resulting in substantial personal and financial costs. In most cases, these infections are associated with the hardware used to stabilize the fusion. Traditionally molded or machined polyether ether ketone (PEEK) cages are widely used for this purpose due to PEEK’s strength, elastic modulus comparable to bone, biocompatibility, and radiolucency. However, traditional PEEK cages and common alternatives are prone to spinal infection. Silicon nitride (Si3N4) spacers have been used in other spinal applications with an excellent antimicrobial performance history (i.e., only 0.006% of implants have been associated with infection), and they provide superior osseointegration compared to other materials. Unfortunately, Si3N4 is not ideal for stabilizing spinal fusions because the material may be susceptible to subsidence and brittle fracture. In this Phase I STTR, SINTX Technologies, in collaboration with Drexel University and Thomas Jefferson University, will combine the antimicrobial and osseointegrative properties of Si3N4 with the strength and elasticity of PEEK to develop novel 3-D-printed antimicrobial cervical cages. Development and commercialization of a 3DP Si3N4-PEEK cervical cage would address a critical unmet clinical need for an antimicrobial spinal fusion stabilizer that promotes osseointegration, withstands in vivo loading, and facilitates imaging. Aim 1. Design a 3DP Si3N4-PEEK cervical cage that meets the static loading requirements of ASTM F2077. Milestone: Demonstrate static compression, shear, and torsion strength of 3DP Si3N4-PEEK’s porous cages that meets or exceeds the guidelines for cervical cages established by ASTM F2077 and benchmarked for many cage manufacturers in the literature. Aim 2. Determine antibacterial activity and osteoblast proliferation/maturation as a function of Si3N4 percentage. Milestone: A >1.5 log reduction in bacterial colonization while retaining osteoblastic proliferation/maturation. Impact—This project is expected to demonstrate the feasibility of creating cervical cages that simultaneously retain the superior radiological and biomechanical qualities of 3DP PEEK biomaterials while preserving the osseointegrative and antimicrobial qualities of Si3N4. A Phase II STTR or SBIR would advance the 3DP Si3N4-PEEK cervical cage to IDE-enabling studies, including assessments of fatigue performance, subsidence resistance, and preclinical performance in a full-scale rigorously powered in vivo model. Rationally designed antibacterial spinal cages that reliably reduce infection are critical, especially given the personal and financial costs of failed fusions as well as the increasing numbers of spinal fusions in the US due to our aging population. Milestone for Progression to Phase II— Delivery of a 3DP Si3N4-PEEK cervical cage that (1) meets the static loading requirements of ASTM F2077, (2) meets minimum performance thresholds for osseointegration, and (3) meets minimum performance thresholds for antibacterial activity. Quantitative targets are included in the Approach.