SBIR-STTR Award

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.

Public Health Relevance Statement:
PROJECT NARRATIVE Femur fracture fixation is one of the most common orthopedic procedures. Of the 235,000 operable fractures of these longs bones each year in the USA, about five to ten percent will not heal, resulting in nonunions and/or malunions, or will have delayed healing. It has been reported that femoral nonunion has a severe debilitating effect on patient health and wellbeing and is incredibly costly to the healthcare system and society due to the loss of work and quality of life. This problem is especially bad for patients who have risk factors such as diabetes or tobacco use. 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. The poor healing problems with lower extremities are especially problematic for our Wounded Warfighters injured by IED explosions. The Evoke Medical solution will provide a non-pharmacological, cost-effective way to create intramedullary nail implants that will provide bone healing electrical stimulation as well as post-operative healing monitoring from a human's body motion. Our platform technology generates Mechanically Synced Electrical Stimulation (MSES) to help these patients heal better and faster, with each step they take. Utilizing human powered technology, this implant can provide therapeutic bone healing stimulation right to the fracture site and signal to the physician the healing progression for earlier intervention; all without a battery or external brace relying on patient compliance. Our long bone fracture fixation device will give surgeons a way to enhance their patient care, while simultaneously reducing cost of care and improving patient outcomes.

Project Terms:
Animals; Biomechanics; biomechanical; bone; Data Collection; Diabetes Mellitus; diabetes; Diagnosis; Electric Stimulation; Electrical Stimulation; electrostimulation; Electrodes; Explosion; Fatigue; Lack of Energy; Femoral Fractures; femur fracture; Femur; Fracture Fixation; Skeletal Fixation; Fracture; bone fracture; Future; Patient Care; Patient Care Delivery; Goals; Growth; Generalized Growth; Tissue Growth; ontogeny; Health; Healthcare Systems; Health Care Systems; Health Personnel; Health Care Providers; Healthcare Providers; Healthcare worker; health care personnel; health care worker; health provider; health workforce; healthcare personnel; medical personnel; treatment provider; Recording of previous events; History; histories; Human; Modern Man; implantable device; biomedical implant; implant device; indwelling device; Infection; Intramedullary Nailing; Lower Extremity; Lower Limb; Membrum inferius; Marketing; Medical Device; Methods; Military Personnel; Armed Forces Personnel; Military; military population; Motion; Nail plate; Nails; Persons; Osteogenesis; Bone Formation; bone tissue formation; Patients; Personal Satisfaction; well-being; wellbeing; Physicians; Postoperative Period; Post-Operative; Postoperative; Production; Quality of life; QOL; Research; Risk; Risk Factors; Safety; Sheep; Ovine; Ovis; Signal Transduction; Cell Communication and Signaling; Cell Signaling; Intracellular Communication and Signaling; Signal Transduction Systems; Signaling; biological signal transduction; Societies; sound; Spinal Fusion; Spondylosyndeses; Technology; Testing; Time; Titanium; Ti element; X-Ray Computed Tomography; CAT scan; CT X Ray; CT Xray; CT imaging; CT scan; Computed Tomography; Tomodensitometry; X-Ray CAT Scan; X-Ray Computerized Tomography; Xray CAT scan; Xray Computed Tomography; Xray computerized tomography; catscan; computed axial tomography; computer tomography; computerized axial tomography; computerized tomography; non-contrast CT; noncontrast CT; noncontrast computed tomography; Translating; Woman; Work; Generations; measurable outcome; outcome measurement; Outcome Measure; customs; Custom; Electric Resistance; Electrical Resistance; injuries; Injury; improved; Site; Surface; Chronic; Clinical; Phase; Physiologic; Physiological; Medical; Ensure; Evaluation; long bone; Failure; diabetic; Licensing; Early Intervention; Human Figure; Human body; Funding; Therapeutic; Shapes; Mechanics; mechanic; mechanical; Frequencies; Complex; System; Orthopedic Procedures; Tobacco use; Tobacco Consumption; tobacco product use; Operative Surgical Procedures; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Surgeon; experience; success; Finite Element Analysis; Finite Element Analyses; novel; Patient Self-Report; Self-Report; Devices; Reporting; Modeling; Property; response; miniaturize; miniaturized; Second Look Surgery; Second Look; Surgical Revision; Bone Growth; preventing; prevent; Load Bearing; Weight Bearing; Weight-Bearing state; Patient Compliance; patient adherence; patient cooperation; therapy compliance; therapy cooperation; treatment compliance; compliance behavior; Address; Data; in vivo; Patient-Focused Outcomes; Patient outcome; Patient-Centered Outcomes; patient oriented outcomes; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Validation; validations; Pathologic; Monitor; Development; developmental; Output; cost; healing; injured; designing; design; Outcome; cost effective; Population; Implant; implantation; bone wound healing; osseous wound healing; bone healing; prototype; commercialization; patient population; standard of care; verification and validation; mechanical load; care costs; tobacco user; manufacturability; phase 2 evaluation; phase II evaluation; phase II testing; phase 2 testing; Healing abnormal; Healing delayed; Impaired healing; early clinical trial; early phase clinical trial; warfighter; combat related injury; combat injury; bone fracture repair; Fracture Healing; bone fracture healing; fracture repair; design,build,test; manufacture; technology platform; technology system