Commercialization of an Improved Treatment of Extremity Fractures Using a Regenerative Bone Adhesive to Accelerate Bone Healing in Aging Patients

使用再生骨粘合剂加速老年患者骨愈合的四肢骨折改进治疗方法的商业化

• 批准号: 10822079
• 负责人: Brian Hess
• 金额: $ 174.67万
• 依托单位: REVBIO, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10822079
• 关键词: Acceleration; Address; Adhesives; Adverse event; Age; Aging; Anesthesia procedures; Animals; Award; Biological; Cadaver; Carpal Tunnel Syndrome; Clinical Investigator; Clinical Research; Clinical Trials; Complex Regional Pain Syndromes; Complication; Defect; Development; Distal; Elderly; Electroplating; Enrollment; Equation; Event; Failure; Fatigue; Filler; Formulation; Fracture; Fracture Fixation; Funding; Goals; Good Clinical Practice; Grant; Guidelines; Human; Incidence; Infection; Injury; Institution; Intervention; Life; Limb structure; Lower Extremity; Market Research; Metals; Methods; Mission; Modeling; Multi-Institutional Clinical Trial; National Institute on Aging; Operative Surgical Procedures; Orthopedics; Oryctolagus cuniculus; Outcome Study; Patients; Performance; Periodicity; Persons; Phase; Population; Process; Quality of life; Radius Fractures; Recurrence; Regional Anatomy; Reporting; Research; Risk; Rupture; Safety; Sampling; Second Look Surgery; Sheep; Site; Small Business Innovation Research Grant; Specific qualifier value; Sterility; Sterilization; Surgeon; Syndrome; System; Techniques; Tendon structure; Testing; Training; Trauma; Upper Extremity; Validation; Work; biomaterial compatibility; bone; bone fracture repair; bone healing; clinical research site; commercialization; cost; design verification; experience; falls; first-in-human; fragility fracture; healing; image guided; implant design; improved; irritation; mortality; novel; patient population; pre-clinical research; preclinical development; preclinical study; prevent; primary endpoint; product development; programs; radiological imaging; regenerative; safety study; sample fixation; standard of care; standing height; usability; validation studies

Project Abstract/Summary In the U.S., about 2.1 million people experience a fragility fracture each year. This number is expected to double or triple by 2040 as the population ages. Injuries in the upper and lower extremities equate to more than 40% of fragility fractures, and experiencing a prior fracture is associated with an 86% increased risk of recurrence. Falls from standing height and other low-energy trauma account for 87% of all orthopedic fractures among the elderly. External fixation, percutaneous pinning, and open reduction internal fixation with locking plates are interventions that are currently being used to treat extremity fractures. Despite advances in surgical technique and implant design, nonunion, malunion, and hardware failure continue to remain a significant cause of revision surgery in the elderly. Complication rates as high as 36% have been reported and involve onset of carpal tunnel syndrome, complex regional pain syndrome, tendon irritation and rupture, and deep infection. To address this problem, RevBio developed Tetranite® (TN), a novel bone adhesive that can fill gaps in bone, fixate bone fragments, and accelerate healing through its osteoconductive effects. TN can be used as an adjunct to traditional hardware fixation to provide immediate load sharing between the metal plate and screw systems, and bone. It provides additional stability by enhancing fracture stabilization to achieve better healing and prevents hardware failure. It can also be injected percutaneously a standalone method of fixation providing an option to surgically treat fractures without the need for open reduction, metal hardware, or anesthesia. Proposed work to treat extremity fractures in the elderly will bridge off existing late-stage development of TN supported by a SBIR Phase II award from the National Institutes of Aging entitled, “Improved Treatment of Distal Radius Fractures Using an Image-Guided, Percutaneous Delivery of a Novel Bone Adhesive” (R44 AG060881- 02). This grant enabled formulation optimization and conduction of user validation studies with surgeons (Aim 1) and a pivotal animal study in sheep (Aim 2) to demonstrate safety and efficacy of TN. This project is focused on a specific indication to treat distal radius fractures; however, based on discussions with FDA and surgeons, the impact and value of the material could be expanded to a wider set of indications across all metaphyseal fractures in the upper and lower extremities for this same patient population. Therefore, this grant would provide additional funding to conduct market research and supplemental pre-clinical development costs to expand its use to these additional anatomic regions. This funding would also enable completion of biocompatibility, sterilization, packaging, and shelf-life validations to finish late-stage development, enabling RevBio to file an IDE, and execute a clinical study with TN as an adjunct to hardware. The overarching goal of this program is to build off successful Phase II research and to execute Aim 1 and Aim 2 to lead to product regulatory approval for commercialization. Long term, RevBio’s mission is to commercialize TN in order to provide surgeons with a novel product that will enhance fixation, accelerate healing, and reduce complications associated with extremity fractures in the elderly.

项目摘要/总结 在美国，每年约有 210 万人遭受脆性骨折。这个数字预计将增加一倍 或随着人口老龄化，到 2040 年将增加两倍。上肢和下肢损伤相当于40%以上 脆性骨折，并且先前经历过骨折与复发风险增加 86% 相关。瀑布 站立高度和其他低能量创伤造成的老年人骨科骨折占 87%。 干预措施有外固定、经皮钉扎和切开复位锁定钢板内固定 目前用于治疗四肢骨折。尽管手术技术和植入物不断进步 设计、骨不连、畸形愈合和硬件故障仍然是修复手术的重要原因 老年人。据报道，并发症发生率高达 36%，其中包括腕管综合征， 复杂的局部疼痛综合征、肌腱刺激和断裂以及深部感染。 为了解决这个问题，RevBio 开发了 Tetranite® (TN)，一种新型骨粘合剂，​​可以填充骨间隙， 固定骨头碎片，并通过其骨传导作用加速愈合。 TN可作为辅助剂 与传统的硬件固定相比，可在金属板和螺钉系统之间提供直接的负载共享， 和骨头。它通过增强骨折稳定性来提供额外的稳定性，以实现更好的愈合和 防止硬件故障。它也可以经皮注射作为一种独立的固定方法，提供 无需切开复位、金属硬件或麻醉即可进行手术治疗骨折的选择。 治疗老年人四肢骨折的拟议工作将弥补 TN 现有的后期发展 获得美国国家老龄化研究所颁发的 SBIR 第二阶段奖项的支持，该奖项名为“改善远端远端治疗” 使用图像引导、经皮输送新型骨粘合剂治疗桡骨骨折”（R44 AG060881- 02）。这笔赠款使外科医生能够优化配方并进行用户验证研究（目标 1） 以及一项针对绵羊的关键动物研究（目标 2），以证明 TN 的安全性和有效性。该项目重点关注 治疗桡骨远端骨折的具体适应症；然而，根据与 FDA 和外科医生的讨论， 该材料的影响和价值可以扩展到所有干骺端骨折的更广泛的适应症 对于同一患者群体的上肢和下肢。因此，这笔赠款将提供额外的 进行市场研究的资金和补充临床前开发成本，以将其用途扩大到这些领域 额外的解剖区域。这笔资金还将能够完成生物相容性、灭菌、 包装和保质期验证以完成后期开发，使 RevBio 能够归档 IDE 并执行 一项以 TN 作为硬件辅助的临床研究。该计划的总体目标是建立成功的 第二阶段研究并执行目标 1 和目标 2，以获得产品商业化的监管批准。 从长远来看，RevBio 的使命是将 TN 商业化，以便为外科医生提供一种新颖的产品， 加强固定，加速愈合，减少老年人四肢骨折的并发症。