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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
2P20GM103444-06
Application #
8742734
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-04-30
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Clemson University
Department
Type
DUNS #
City
Clemson
State
SC
Country
United States
Zip Code
29634
Hensley, Austin; Rames, Jess; Casler, Victor et al. (2018) Decellularization and characterization of a whole intervertebral disk xenograft scaffold. J Biomed Mater Res A 106:2412-2423
Parasaram, Vaideesh; Nosoudi, Nasim; Chowdhury, Aniqa et al. (2018) Pentagalloyl glucose increases elastin deposition, decreases reactive oxygen species and matrix metalloproteinase activity in pulmonary fibroblasts under inflammatory conditions. Biochem Biophys Res Commun 499:24-29
Prim, David A; Menon, Vinal; Hasanian, Shahd et al. (2018) Perfusion Tissue Culture Initiates Differential Remodeling of Internal Thoracic Arteries, Radial Arteries, and Saphenous Veins. J Vasc Res 55:255-267
Kourtidis, Antonis; Anastasiadis, Panos Z (2018) Close encounters of the RNAi kind: the silencing life of the adherens junctions. Curr Opin Cell Biol 54:30-36
Dunton, Cody L; Purves, J Todd; Hughes Jr, Francis M et al. (2018) Elevated hydrostatic pressure stimulates ATP release which mediates activation of the NLRP3 inflammasome via P2X4 in rat urothelial cells. Int Urol Nephrol 50:1607-1617
Yu, Jin; Zhu, Hong; Taheri, Saeid et al. (2018) Impact of nutrition on inflammation, tauopathy, and behavioral outcomes from chronic traumatic encephalopathy. J Neuroinflammation 15:277
Dhulekar, Jhilmil; Simionescu, Agneta (2018) Challenges in vascular tissue engineering for diabetic patients. Acta Biomater 70:25-34
Bae, Sooneon; DiBalsi, Michael J; Meilinger, Nicole et al. (2018) Heparin-Eluting Electrospun Nanofiber Yarns for Antithrombotic Vascular Sutures. ACS Appl Mater Interfaces 10:8426-8435
Le Tourneau, Thierry; Le Scouarnec, Solena; Cueff, Caroline et al. (2018) New insights into mitral valve dystrophy: a Filamin-A genotype-phenotype and outcome study. Eur Heart J 39:1269-1277
Abramyan, Tigran M; Hyde-Volpe, David L; Stuart, Steven J et al. (2017) Application of advanced sampling and analysis methods to predict the structure of adsorbed protein on a material surface. Biointerphases 12:02D409

Showing the most recent 10 out of 127 publications