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

项目摘要/摘要 在美国，每年约有210万人经历脆性骨折。预计这一数字将翻一番 到2040年，随着人口老龄化，这一数字将增加两倍。上肢和下肢的损伤相当于40%以上的 脆性骨折和既往骨折与复发风险增加86%相关。福尔斯 站立高度和其他低能量创伤占老年人所有骨科骨折的87%。 外固定、经皮穿针固定和切开复位锁定钢板内固定是介入治疗 目前被用于治疗四肢骨折。尽管手术技术和植入物的进步 设计、骨不连、畸形愈合和内固定器械失效仍然是翻修手术的重要原因， 老人据报道，并发症发生率高达36%，包括腕管综合征， 复杂区域疼痛综合征、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），一种新型的骨粘合剂，可以填充骨间隙， 固定骨碎片，并通过其骨传导作用加速愈合。TN可用作辅助剂 对于传统的硬件固定以在金属板和螺钉系统之间提供即时的载荷分担， 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， 防止硬件故障。它也可以作为一种独立的固定方法， 选择手术治疗骨折，而不需要开放复位，金属硬件，或麻醉。 治疗老年人四肢骨折的拟议工作将弥合现有的晚期TN发展 由国家老龄研究所的SBIR第二阶段奖支持，题为“改善远端 使用图像引导经皮输送新型骨粘合剂治疗桡骨骨折”（R44 AG 060881- 02）。该补助金使配方优化和外科医生的用户验证研究得以进行（目标1） 以及一项关键的绵羊动物研究（目的2），以证明TN的安全性和有效性。该项目的重点是 治疗桡骨远端骨折的特定适应症;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适应症 在同一个病人群体的上肢和下肢。因此，这笔赠款将提供额外的 资金进行市场研究和补充临床前开发费用，以扩大其使用这些 其他解剖区域。这笔资金还将使生物相容性，灭菌， 包装和保质期验证，以完成后期开发，使RevBio能够提交IDE，并执行 将TN作为硬件辅助的临床研究。该计划的首要目标是建立成功的 第二阶段的研究，并执行目标1和目标2，导致产品的商业化监管批准。 从长远来看，RevBio的使命是将TN商业化，为外科医生提供一种新的产品， 加强固定，加速愈合，减少老年人四肢骨折相关并发症。

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.