Development of a Piezoelectric Intramedullary Nail for Enhanced Fracture Healing

项目摘要 本阶段SBIR的目标是开发一种组配式压电髓内钉， 骨折愈合和术后数据收集。Evoke Medical的核心技术是创造人类- 利用压电材料产生负载感应功率的动力可植入装置。这种力量可以 然后用于各种目的：电刺激骨生长和/或负荷感测以跟踪愈合 进展通过前SBIR第一阶段和第二阶段的支持，我们已经成功地开发和 制造了一个完全集成的压电脊柱融合植入物。嵌入式压电发电机和 小型化电路将患者运动转换为机械同步的负性刺激， 通过外部钛电极愈合部位。通过两项绵羊研究，已证明这些负荷 诱导骨诱导脊柱融合植入物刺激更快更好的脊柱融合，无病理性骨 阵利用该平台技术，初步设计了一种新型模块化压电陶瓷 髓内（IM）钉已经被证实，并且一种机械上可靠的制造有效的 开发了具有嵌入式电路的压电植入物。Evoke Medical已建立战略合作伙伴关系 这将使我们能够设计、制造和测试压电髓内钉植入物，最终可以在 以合理的成本。 在美国，髓内钉是股骨骨折的首选和最广泛使用的治疗方法。尽管 骨折不愈合是一种慢性疾病，造成昂贵的， 对患者、医生和整个医疗系统造成严重后果。一般来说，5- 15%的 在美国，所有骨折的骨折固定术患者都会出现某种形式的受损愈合。一些 骨折类型和患者人群报告的骨不连率高达54%， 导致每年超过100，000例骨折进展为骨不连。治愈的速度可能会很慢， 患者，尤其是烟草使用者和糖尿病患者。烟草使用者已被证明有≥1.6x 与不吸烟者和糖尿病患者相比， a畸形愈合的风险增加≥ 6倍。植入式直流（DC）电刺激具有超过30年的临床经验 增强骨愈合的历史，但需要植入电池和具有挑战性的形状因素， 广泛使用。I期提案的前提是，具有集成负载的组配式髓内钉植入物 与电流相比，诱导DC刺激将促进更快和更坚固的骨折愈合 护理标准。 本阶段I的总体目标是降低压电组配式髓内钉设计概念的风险， 最差情况下的机械强度和电输出角度。具体来说，我们将证明， 与其他新型髓内钉植入物集成的定制环形压电发生器设计的功率输出 在预期的临床应用中，组件可以在生理负载下产生足够的电刺激。 设置（低频和有限的承重）。此外，我们将从机械设计评估 组装的植入物可承受最差情况生物力学载荷和临床使用载荷的观点 场景（例如，弯曲和冲击）。成功的结果将是经过验证的髓内钉原型， 集成压电发生器，可以进行到第二阶段的努力，以证明安全性和有效性的 机械同步电刺激在绵羊的研究。 这项工作的结果将为第二阶段的资金奠定基础，以集成和集成电路和电极 组件纳入髓内钉设计，并继续进行监管所需的验证和确认测试 评价作为未来第二阶段工作的一部分，我们将研究增加传感电路来跟踪愈合 研究进展并完成绵羊体内验证研究，以证明继续推进商业化。 随后，将筹集额外资金，以完成扩大监管所需的早期临床试验。 关于增强骨折愈合和诊断成功结局的声明。目标IM指甲市场 超过6.58亿美元，复合年增长率为4.7%。假设申报器械可增加 成功愈合和减少愈合时间，以及给病人和医疗保健提供者定量 无需昂贵的CT扫描或有偏见的患者自我报告。这将减少整体 护理成本和人类痛苦，如前所述，可以做出数据驱动的术后决策， 骨不连和额外的翻修手术。

PROJECT SUMMARY The objective of this Phase I SBIR is to develop a modular piezoelectric intramedullary nail for enhance fracture healing and post-operative data collection. Evoke Medical’s core technology is to create human- powered implantable devices that utilize piezoelectric materials to generate load-induced power. That power can then be used for various purposes: electrical stimulation of bone growth and/or load-sensing to track healing progression. Through former SBIR Phase I and Phase II support, we have successfully developed and manufactured a fully integrated piezoelectric spinal fusion implant. The embedded piezogenerator and miniaturized circuitry convert patient motion to mechanically synced electronegative stimulation delivered to the healing site via external titanium electrodes. Through two ovine studies, it has been proven that these load induced osteoinductive spinal fusion implants stimulate faster and better spinal fusion without pathologic bone formation. Utilizing this platform technology, a preliminary design concept for a novel modular piezoelectric intramedullary (IM) nail has been demonstrated and a mechanically sound method of manufacturing efficient piezoelectric implants with embedded circuitry was developed. Evoke Medical has formed strategic partnerships that will allow us to design, build and test piezoelectric IM nail implants that can eventually be manufactured in volume at a reasonable cost. Intramedullary nails are the preferred and most widely used treatment for femoral fractures in the US. Despite reported generally good outcomes, fracture nonunion is a chronic medical condition that creates costly and severe consequences for patients, physicians, and the medical system at large. In general, 5-15 percent of fracture fixation patients for all bone fractures in the USA develop some form of compromised union. Some fracture types and patient populations have a larger number of reported nonunion rates as high as 54 percent, resulting in over 100,000 fractures progressing to nonunion annually. The rate of healing can be slow in all patients, especially in tobacco users and patients with diabetes. Tobacco users have been shown to have ≥1.6x greater risk for nonunion than those who do not use tobacco and people with diabetes have been shown to have a ≥6x greater risk for malunion. Implantable direct current (DC) electrical stimulation has over 30+ year clinical history of enhancing bone healing but need for an implanted battery and challenging form factors have limited widespread use. The premise of the Phase I proposal is that a modular IM nail implant with integrated load induced DC stimulation will promote a faster and more robust fracture union in comparison to the current standard of care. The overall goal of this Phase I is to de-risk the piezoelectric modular IM nail design concept, from both a worst-case mechanical strength and electrical output perspective. Specifically, we will prove that the power output from a custom ring piezogenerator design integrated with the other novel IM nail implant components can produce sufficient electrical stimulation under the physiological loading in expected clinical settings (low frequency and limited weight bearing). Additionally, we will assess from a mechanical design standpoint that the assembled implant can withstand worst case biomechanical loading and clinical use loading scenarios (e.g., bending and impact). The outcome of a successful effort will be a verified IM nail prototype with integrated piezogenerator that can be carried into a Phase II effort to prove safety and efficacy of the mechanically synced electrical stimulation in an ovine study. The results of this work will set the stage for Phase II funding to integrate and miniaturize the circuit and electrode components into the IM nail design and proceed with the verification and validation testing needed for regulatory evaluation. As part of the future Phase II work, we will investigate the addition of sensing circuitry to track healing progression and complete in vivo validation ovine studies to justify moving forward with commercialization. Following, additional funding will be raised to complete early clinical trials required for expanded regulatory claims around enhancement of fracture healing and diagnosis of successful outcomes. The target IM nail market is over $658M with a compound annual growth rate of 4.7%. The proposed device is hypothesized to increase success of healing and decrease time to heal, as well as give patients and healthcare providers quantitative outcome measures without expensive CT scans or biased patient self-reporting. This would decrease overall cost of care and human suffering, as earlier, data driven post-operative decisions could be made, preventing nonunion and additional revision surgeries.