Developing Luminescent Strain Sensors to Evaluate and Monitor Osteoinductive Ther

开发发光应变传感器来评估和监测骨感应热

• 批准号: 8742734
• 负责人: JEFFREY N ANKER
• 金额: $ 19.75万
• 依托单位: CLEMSON UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8742734
• 关键词: Allografting; Animals; Autopsy; Biomechanics; Biomedical Engineering; Bone callus; Cells; Centers of Research Excellence; Clinical; Complication; Coupled; Data; Defect; Devices; Diagnostic radiologic examination; Effectiveness; Electronics; Evaluation; Fiber; Fracture; Fracture Fixation; Fracture Healing; Goals; Healed; Histology; Human; Image; Image Analysis; Implant; In Situ; In Vitro; Incidence; Individual; Infection; Internal Fixators; Measurement; Measures; Mechanics; Medial; Mentors; Modeling; Molecular; Monitor; Muscle; Natural regeneration; Operative Surgical Procedures; Optics; Orthopedics; Oryctolagus cuniculus; Osteotomy; Pain; Patients; Physicians; Pilot Projects; Point-of-Care Systems; Population; Principal Investigator; Property; Reading; Research; Research Personnel; Risk; Simulate; Solutions; Specimen; Spectrum Analysis; Surgeon; System; Techniques; Testing; Thick; Tibial Fractures; Tissues; Titania; Titanium; Walking; Wireless Technology; base; bioimaging; bone; bone healing; bone morphogenetic protein 2; cost; healing; in vivo; innovation; innovative technologies; instrument; limb fracture; luminescence; musculoskeletal injury; novel; osteogenic; periostin; programs; regenerative; repaired; research study; sample fixation; sensor; tibia; tool

We will develop a noninvasive technique to measure strain on orthopedic plates in order to quantify the mechanical stiffness of bone fracture calluses and to assess the effectiveness of osteoinductive treatments. Over 28 million musculoskeletal injuries are treated annually in the US including 2 million fracture-fixation surgeries. Limb fractures with large segmental defects are especially challenging to treat and have high rates of non-union and revision surgeries. A key goal in orthopedic research is to develop osteoinductive treatments (e.g., using BMPs, or periostin) to accelerate healing and reduce complication rates. To help researchers develop and optimize these regenerative treatments, and to help physicians evaluate healing in individual patients, there is an urgent need for techniques to quantify mechanical properties of fracture calluses in vivo. Although animal studies have used transcutaneously connected resistive strain gauges to measure decreasing plate strain during healing as the fracture callus stiffens and increasingly shares the load, the connecting wires would be infection risks and impractical for human patients. We will develop a novel, elegant, low-cost, sensitive, noninvasive, and highly versatile solution based on luminescence spectroscopy. While optical displacements are commonly measured in vitro via image analysis, our approach is novel in that we perform sensitive measurement through tissue by measuring spectral changes in essentially background-free, deeply penetrating upconversion luminescence. The measurements can be made using a portable spectrometer system for point-of-care measurements, and the gauges have a low profile for simple incorporation into or onto existing plates. We will calibrate the sensor by measuring the luminescence spectrum as a function of load (4- point bending and axial compression) in a plated tibia-equivalent specimen and evaluate strain sensitivity through various tissue thicknesses. We will then implant a titanium dynamic-compression plate with a luminescent strain gauge into 4 groups of rabbits in a tibial osteotomy model with varying defect sizes to control healing rate. We will measure the implant strain in each group over a period of 6 weeks and compare results with in vivo �-CT in the Bioengineering and Bioimaging Core, as well as histology in the Cell, Tissue, and Molecular Analyses Core. We will then repeat the experiments for rabbits treated with osteogenic molecules (BMP-2 or periostin) and compare results with untreated animals. Our strong interdisciplinary team, consisting of Dr. Anker (PI), Dr. DesJardins (biomechanical collaborator), Dr. Chip Norris (another targeted COBRE PI developing osteoinductive periostin treatments), Dr. Tom Pace (orthopedic surgeon and clinical mentor), and academic advisors Drs. Bob Latour, Roger Markwald, and Naren Vyavahare, will bring this innovative technology from a novel spectroscopic tool to a noninvasive sensor to assess in vivo bone healing.

我们将开发一种非侵入性技术来测量矫形板的应变，以量化 骨折愈伤组织的机械硬度并评估骨诱导治疗的有效性。 美国每年治疗超过 2800 万例肌肉骨骼损伤，其中 200 万例骨折固定 具有大节段缺损的肢体骨折治疗起来尤其困难，而且发生率很高。 骨不连和翻修手术的一个关键目标是开发骨诱导治疗。 （例如，使用 BMP 或骨膜素）加速愈合并降低并发症发生率以帮助研究人员。 开发和优化这些再生疗法，并帮助医生评估个人的康复情况 对于患者来说，迫切需要量化体内骨折愈伤组织机械特性的技术。 尽管动物研究已经使用经皮连接的电阻应变计来测量减少的 愈合过程中，随着骨折愈伤组织变硬并逐渐分担负载，连接线会产生板应变 对于人类患者来说会有感染风险且不切实际。我们将开发一种新颖、优雅、低成本、 基于发光光谱的灵敏、非侵入性和高度通用的解决方案。 位移通常通过图像分析在体外测量，我们的方法是新颖的，因为我们执行 通过组织进行灵敏的测量，通过测量基本无背景的光谱变化，深入 可以使用便携式光谱仪进行穿透上转换发光的测量。 用于现场护理测量的系统，并且仪表具有低调的外形，可以简单地集成到或集成到 我们将通过测量作为负载函数的发光光谱来校准传感器 (4- 点弯曲和轴向压缩）在电镀胫骨等效样本中并评估应变敏感性 然后，我们将植入带有钛动态压缩板的各种组织厚度。 将发光应变计植入 4 组具有不同缺损尺寸的胫骨截骨模型中的兔子，以 我们将在 6 周内测量各组的种植体应变并进行比较。 生物工程和生物成像核心中的体内 �-CT 以及细胞、组织、 然后我们将对经过成骨治疗的兔子重复实验。 分子（BMP-2 或骨膜素）并将结果与​​未经治疗的动物进行比较，我们强大的跨学科团队， 由 Anker 博士（PI）、DesJardins 博士（生物力学合作者）、Chip Norris 博士（另一位目标 COBRE PI 骨诱导骨膜素治疗），Tom Pace 博士（骨科医生和开发临床 导师）和学术顾问 Bob Latour 博士、Roger Markwald 和 Naren Vyavahare 博士将带来这个 从新型光谱工具到无创传感器的创新技术，用于评估体内骨愈合。