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 观察骨折骨痂的机械硬度，并评估骨诱导治疗的有效性。 在美国，每年有超过2800万人接受肌肉骨骼损伤的治疗，其中200万人接受骨折固定 手术。伴有较大节段性缺陷的四肢骨折的治疗难度特别大，且发生率较高。 不愈合手术和翻修手术。骨科研究的一个关键目标是开发骨诱导疗法。 (例如，使用BMPs或Periostin)以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疗法，并帮助医生评估个人的愈合情况 对于患者来说，迫切需要技术来量化体内骨折骨痂的力学特性。 尽管动物研究已经使用经皮肤连接的电阻应变计来测量下降 愈合过程中的钢板应变，因为骨折的骨痂变硬，并越来越多地分担负荷，连接的电线 会有感染风险，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、 基于发光光谱的灵敏、非侵入性和高通用性的解决方案。而光学的 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 通过测量基本无背景、深度的光谱变化来通过组织进行灵敏的测量 穿透式上转换发光。这些测量可以使用便携式光谱仪进行。 用于医疗护理点测量的系统，该量规具有低轮廓，便于装入或装入 现有的车牌。我们将通过测量发光光谱作为负载的函数来校准传感器(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动力加压钢板 4组兔在不同大小的胫骨截骨模型中植入发光应变片 控制治愈率。我们将在6周的时间内测量每组种植体的应变，并比较 结果与体内�-CT在生物工程和生物成像核心，以及组织学在细胞，组织， 和分子分析核心。然后，我们将对接受成骨治疗的兔子重复实验。 分子(BMP-2或Periostin)，并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(另一个目标)组成 Cobre Pi正在开发骨诱导Perostin疗法)，Tom Pace博士(整形外科医生和临床 Mentor)，以及学术顾问Bob Latour、Roger Markwald和Naren Vyavahare博士将带来 从一种新的光谱工具到一种非侵入性传感器的创新技术，用于评估活体骨愈合。

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.