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

项目摘要 脊柱融合术是治疗持续性颈部和背部疼痛的标准疗法，但用于稳定的硬件 这种融合可以窝藏甚至促进细菌，导致持续的，难以治疗的感染，这是昂贵的 并损害患者健康。在可用于脊柱融合的材料中，聚醚醚酮（PEEK） 融合器因其强度、生物相容性和射线可透性而脱颖而出，但与其他材料一样， 易受脊椎感染氮化硅（Si 3 N4）间隔物已经用于其他脊柱应用中， 他们因感染引起的可报告不良事件的发生率远低于行业标准， 由于其潜在的下沉和脆性骨折，是稳定脊柱融合的理想选择。为了解决这个 SINTX利用第一阶段SBIR资金开发和测试了3D打印的Si 3 N4-PEEK材料， 结合了Si 3 N4的抗菌和骨整合特性以及PEEK的强度和弹性。 在第二阶段SBIR中，SINTX建议使用这种材料开发3D打印的抗菌脊柱融合术 融合器可促进骨整合，承受体内负荷，并有助于成像。该项目包括 正常和污染的长期生物力学性能和体内融合性能测试 操作场景。这些活动的成功完成将使SINTX能够准备510（k）上市前 FDA的通知申请。SINTX预计3D打印的进一步开发和商业化 Si 3 N4-PEEK脊柱融合器将为骨科医生提供一种高性能融合器械， 大大降低了融合相关感染的发生率。 目标1。通过正式设计和过程风险将潜在设计和制造危害降至最低 根据ISO 14971进行管理分析。里程碑：完成设计FMEA和 根据ISO 14971进行过程FMEA，以最大限度地降低与新型颈椎融合器和设计冻结相关的风险。 目标二。验证最终3DP Si 3 N4-PEEK颈椎融合器是否满足静态和疲劳载荷要求 ASTM F2077的要求和ASTM F2267的沉降要求。里程碑：遵循 目标1中的设计冻结，证明静态和疲劳压缩、剪切和扭转强度以及沉陷 最终3DP Si 3 N4-PEEK多孔椎间融合器的阻力符合或超过颈椎融合器指南 由ASTM F2077和ASTM F2267建立，并在文献中为许多椎间融合器制造商设定基准。 目标3。确定抗微生物活性（实验组）和体内生物相容性， 山羊模型中3DP Si 3 N4-PEEK颈椎融合器的骨整合（生物相容性GLP组） 颈椎融合术里程碑：最终、包装和确认的植入物将通过ISO 10993中的要求。 3DP Si 3 N4-PEEK植入物将具有生物相容性、骨长入、融合和抗感染性 与对照3DP PEEK椎间融合器相当或更好。

PROJECT SUMMARY Spinal fusion is the standard treatment for persistent neck and back pain, but the hardware used to stabilize the fusion can harbor or even promote bacteria that lead to persistent, difficult-to-treat infections that are costly and damaging to patient health. Among the available materials for spinal fusion, polyether-ether-ketone (PEEK) cages stand out due to their strength, biocompatibility, and radiolucency, but like other materials, they are susceptible to spinal infections. Silicon nitride (Si3N4) spacers have been used in other spinal applications where their rates of reportable adverse events due to infection are much lower than industry norms, but they are not ideal for stabilizing spinal fusions due to their potential for subsidence and brittle fracture. To address this challenge, SINTX used Phase I SBIR funding to develop and test a 3D-printed Si3N4-PEEK material that incorporates the antimicrobial and osseointegrative properties of Si3N4 with the strength and elasticity of PEEK. In this Phase II SBIR, SINTX proposes to use this material to develop a 3D-printed anti-microbial spinal fusion cage that promotes osseointegration, withstands in vivo loading, and facilitates imaging. The project includes long-term biomechanical performance and in vivo fusion property testing in both normal and contaminated operative scenarios. Successful completion of these activities will position SINTX to prepare a 510(k) premarket notification application for FDA. SINTX anticipates further development and commercialization of a 3D-printed Si3N4-PEEK spinal fusion cage will provide orthopedic surgeons a high-performance fusion device that could greatly reduce the incidence of fusion-associated infections. Aim 1. Minimize potential design and manufacturing hazards by formal design and process risk management analyses in accordance with ISO 14971. Milestone: Completion of the design FMEA and process FMEA per ISO 14971 to minimize risks associated with the novel cervical cages and design freeze. Aim 2. Verify that the finalized 3DP Si3N4-PEEK cervical cage meets the static and fatigue loading requirements of ASTM F2077 and subsidence requirements of ASTM F2267. Milestone: Following the design freeze in Aim 1, demonstrate static and fatigue compression, shear, and torsion strength and subsidence resistance of the finalized 3DP Si3N4-PEEK’s porous cage meets or exceeds the guidelines for cervical cages established by ASTM F2077 and ASTM F2267 and benchmarked for many cage manufacturers in the literature. Aim 3. Determine antimicrobial activity (experimental arm) and in vivo biocompatibility and osteointegration (biocompatibility GLP arm) for a 3DP Si3N4-PEEK cervical cage in a caprine model of cervical spinal fusion. Milestone: Final, packaged, and validated implants will pass requirements in ISO 10993. 3DP Si3N4-PEEK implants will have biocompatibility, bone ingrowth, fusion, and resistance to infection comparable to or better than control 3DP PEEK spinal cages.