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

3D 打印氮化硅多孔 PEEK 复合脊柱笼用于抗感染

• 批准号: 10323105
• 负责人: Bryan J. McEntire
• 金额: $ 30.83万
• 依托单位: SINTX TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10323105
• 关键词: 3D Print; Address; Adhesions; Adopted; Advanced Development; Alkaline Phosphatase; Animals; Anti-Bacterial Agents; Area; Back Pain; Benchmarking; Biocompatible Materials; Biomechanics; Bone Regeneration; Cells; Ceramics; Cervical; Clinical; Collaborations; Congenital failure of fusion; Development; Diagnostic radiologic examination; Elasticity; Escherichia coli; Ethers; Fatigue; Financial cost; Foundations; Fracture; Future; Gold; Guidelines; Human; Image; Implant; Incidence; Infection; Joint repair; Ketones; Literature; Longevity; Manufacturer Name; Metals; Modulus; Molds; Neck Pain; Operative Surgical Procedures; Osseointegration; Osteoblasts; Osteocalcin; Patient-Focused Outcomes; Patients; Performance; Phase; Polymers; Printing; Property; Quality of life; Radiology Specialty; Recording of previous events; Research; Resistance; Risk; Savings; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Solid; Speed; Spinal; Spinal Fusion; Staphylococcus epidermidis; Surface; Technology; Temperature; Time; Titanium; Torsion; United States National Institutes of Health; Universities; aging population; antimicrobial; base; biomaterial compatibility; bone; commercialization; design; implant material; improved; in vivo; in vivo Model; medical implant; mineralization; novel; osteoblast proliferation; pre-clinical; preservation; research clinical testing; silicon nitride; standard care

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.

项目摘要——当颈部和背部疼痛变得顽固时，脊柱融合术是黄金标准 然而，高达 12% 的融合因感染而失败，导致大量的个人和经济损失。 在大多数情况下，这些感染与传统上用于稳定融合的硬件有关。 由于 PEEK 的优点，模制或机加工聚醚醚酮 (PEEK) 保持架广泛用于此目的 强度、弹性模量与骨相当，生物相容性和射线可透性却优于传统的 PEEK。 笼子和常见的替代品很容易发生脊柱感染。 其他具有出色抗菌性能历史的脊柱应用（即，只有 0.006% 的植入物具有 与感染有关），并且与其他材料相比，它们提供了更好的骨整合。 不幸的是，Si3N4 并不是稳定脊柱融合的理想选择，因为该材料可能容易受到 在第一阶段 STTR 中，SINTX Technologies 与德雷塞尔大学合作。 和托马斯杰斐逊大学，将 Si3N4 的抗菌和骨整合特性与 利用 PEEK 的强度和弹性开发新型 3D 打印抗菌宫颈融合器。 3DP Si3N4-PEEK 宫颈笼的商业化将解决未满足的关键临床需求 抗菌脊柱融合稳定剂，可促进骨整合、承受体内负荷并促进 目标 1. 设计满足 ASTM 静态负载要求的 3DP Si3N4-PEEK 宫颈融合器。 F2077。里程碑：展示 3DP Si3N4-PEEK 多孔材料的静态压缩、剪切和扭转强度 符合或超过 ASTM F2077 制定的宫颈笼指南并进行基准测试的笼子 文献中许多笼制造商的目标 2. 确定抗菌活性和成骨细胞。 增殖/成熟与 Si3N4 百分比的关系 里程碑：细菌减少 >1.5 个对数。 定殖同时保留成骨细胞增殖/成熟的影响——该项目预计将实现。 证明创建宫颈笼的可行性，同时保留优越的放射学和 3DP PEEK 生物材料的生物力学品质，同时保留骨整合性和抗菌性 II 期 STTR 或 SBIR 将使 3DP Si3N4-PEEK 宫颈融合器能够支持 IDE。 研究，包括疲劳性能、替代抗性和临床前性能的评估 全尺寸严格动力体内模型 合理设计的抗菌脊柱笼，可可靠地减少。 感染至关重要，特别是考虑到融合失败造成的个人和经济成本以及日益增加的 由于人口老龄化，美国的脊柱融合术进展到第二阶段的里程碑—— 交付 3DP Si3N4-PEEK 宫颈融合器，其 (1) 满足 ASTM F2077 的静态负载要求，(2) 满足骨整合的最低性能阈值，并且 (3) 满足最低性能阈值 该方法中包含了抗菌活性的定量目标。