Developing Luminescent Strain Sensors to Evaluate and Monitor Osteoinductive Ther

我们将开发一种非侵入性技术来测量骨科钢板上的应变，以量化 骨折骨痂的机械刚度，并评估骨诱导治疗的有效性。 在美国，每年治疗超过2800万例肌肉骨骼损伤，包括200万例骨固定术 手术四肢骨折合并大段缺损的治疗尤其具有挑战性，且发生率很高 骨不连和翻修手术骨科研究的一个关键目标是开发骨诱导治疗方法 (e.g.,使用BMP或骨膜蛋白）来加速愈合并降低并发症发生率。帮助研究人员 开发和优化这些再生治疗，并帮助医生评估个人的愈合情况， 患者，迫切需要技术来量化体内骨折骨痂的机械性能。 尽管动物研究已经使用跨导连接的电阻应变计来测量减小的 在愈合过程中，随着骨折骨痂变硬并越来越多地分担载荷， 会有感染的风险，对人类患者来说是不切实际的。我们将开发一种新颖，优雅，低成本， 灵敏、无创和高度通用的解决方案。而光学 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 通过测量基本上无背景的、深度的光谱变化， 穿透上转换发光。可以使用便携式光谱仪进行测量 系统，用于现场护理测量，并且仪表具有低轮廓，便于简单地并入或并入 现有板块我们将通过测量作为负载的函数的发光光谱来校准传感器（4- 点弯曲和轴向压缩），并评估应变敏感性 通过不同的组织厚度。然后我们将植入一个钛制动态加压接骨板 在胫骨截骨术模型中，将发光应变计放入4组具有不同缺损尺寸的家兔中， 控制愈合率。我们将在6周的时间内测量每组的种植体应变， 生物工程和生物成像核心的体内β-CT结果，以及细胞，组织， 和分子分析中心然后，我们将对用成骨细胞治疗的兔子重复实验。 分子（BMP-2或骨膜蛋白），并将结果与未处理的动物进行比较。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（另一个目标 COBRE PI开发骨诱导性骨膜蛋白治疗），Tom Pace博士（整形外科医生和临床 导师）和学术顾问博士鲍勃拉图尔，罗杰Markwald和纳伦Vyavahare，将带来这一点 从新型光谱工具到非侵入式传感器的创新技术，以评估体内骨愈合。

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.