Browsing by Subject "bone healing"

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Application of Salubrinal for Bone Fracture Healing
    (Office of the Vice Chancellor for Research, 2014-04-11) Yokota, Hiroki; Lin, Chien-Chi
    The long-term objective of this project is to commercialize a novel synthetic chemical agent, salubrinal, for treatment of bone growth and fracture healing. Bone morphogenetic proteins (BMPs) are clinically administered as growth stimulators for bone fracture healing. However, BMPs are not only expensive, but also stimulate ectopic bone formation and potentially induce cancer. A synthetic chemical agent that permits facile storage and administration could reduce costs, and provide longer shelf-life, and better bone healing outcomes. Currently, no synthetic chemical agents as a stimulator of fracture healing are clinically available. The research team recently identified “salubrinal,” a synthetic chemical agent, as a potential therapeutic stimulator of bone growth and fracture healing. An invention disclosure and a U.S. patent were filed. In this FORCES project, we are examining efficacy of salubrinal using a mouse model of closed tibia fracture. The results strongly indicate that salubrinal can accelerate bone fracture healing.
  • Thumbnail Image
    Item
    Cohousing Male Mice with and without Segmental Bone Defects
    (American Association for Laboratory Animal Science, 2018-04) Rytlewski, Jeffrey D.; Childress, Paul J.; Scofield, David C.; Khan, Faisal; Alvarez, Marta B.; Tucker, Aamir T.; Harris, Jonathan S.; Peveler, Jessica L.; Hickman, Debra L.; Chu, Tien-Min G.; Kacena, Melissa A.; Biomedical Sciences and Comprehensive Care, School of Dentistry
    Spaceflight results in bone loss like that associated with osteoporosis or decreased weight-bearing (for example, high-energy trauma such as explosive injuries and automobile accidents). Thus, the unique spaceflight laboratory on the International Space Station presents the opportunity to test bone healing agents during weightlessness. We are collaborating with NASA and the US Army to study bone healing in spaceflight. Given the unique constraints of spaceflight, study design optimization was required. Male mice were selected primarily because their femur is larger than females’, allowing for more reproducible surgical outcomes. However, concern was raised regarding male mouse aggression. In addition, the original spaceflight study design included cohousing nonoperated control mice with mice that had undergone surgery to create a segmental bone defect. This strategy prompted the concern that nonoperated mice would exhibit aggressive behavior toward vulnerable operated mice. We hypothesized that operated and nonoperated male mice could be cohoused successfully when they were cagemates since birth and underwent identical anesthetic, analgesic, preoperative, and postoperative conditions. Using quantitative behavioral scoring, body weight, and organ weight analyses (Student t test and ANOVA), we found that nonoperated and operated C57BL/6 male mice could successfully be housed together. The male mice did not exhibit aggressive behavior toward cagemates, whether operated or nonoperated, and the mice did not show evidence of stress, as indicated by veterinary assessment, or change in body or proportional organ weights. These findings allowed our mission to proceed (launched February 2017) and may inform future surgical study designs, potentially increasing housing flexibility.
  • Thumbnail Image
    Item
    Effects of Thrombopoietin (TPO) on Longitudinal Mouse Hind Limb Crush Injury Model
    (Office of the Vice Chancellor for Research, 2015-04-17) Rothchild, Greg; Lipking, Kelsey; McKinley, Todd; Kacena, Melissa A.; Sandusky, George E.
    Approximately 645 people suffer from blunt force trauma injury to the femur every day. The recovery time of such injury can last anywhere from 3-6 months. Thrombopoietin (TPO) was used as a growth factor to induce bone and muscle healing. In this study we utilized 9 separate mouse model groups (10 mice per group) were used: Crush PBS, Crush TPO, Surgery PBS, and Surgery TPO at day 3 and day 17, and controls with no surgery/crush/ treatment. Crush models were introduced to hind limb crush injury by a mechanical-gravity driven Einhorn device. Skeletal muscle was harvested from the following sites: experimental impact, experimental adjacent, and normal contralateral skeletal muscle as a control. The muscles were fixed, processed, sectioned, and stained with H&E and Masson’s Trichrome stains. The slides were reviewed for skeletal muscle injury, muscle necrosis, inflammation, muscle repair, and regeneration. In addition, F4/80, an immunostain for macrophages was performed. On microscopic examination at day 3 the most common histologic changes seen were sporadic muscle fiber vacuolation, focal necrosis of varying sizes, muscle contraction bands, and infiltration of macrophages. On day 17, the skeletal muscle injury was generally healed. The main histologic lesions seen were variable sizes of muscle fibers, early fibroplasia, fat infiltration, some macrophages( less than day 3) , satellite cells, and neovascularization. A follow-up immunostain (CD206 specific for M2 double labeled with F4/80) was performed to characterize the macrophages in and around the lesions at day 3. M2 macrophages were seen around the periphery of the lesion and none in the middle of the lesion. There were very minimal differences in M2 numbers between the PBS and TPO treated groups at day 3. In conclusion, comparing the TPO treated mice versus the PBS control group with F4/80 immunostain showed the lesions at both time points were less in the TPO treated mice.
  • Thumbnail Image
    Item
    A Mechatronic Loading Device to Stimulate Bone Growth via a Human Knee
    (MDPI AG, 2016-09-29) Prabhala, Sai Krishna; Chien, Stanley; Yokota, Hiroki; Anwar, Sohel; Department of Mechanical Engineering, School of Engineering and Technology
    This paper presents the design of an innovative device that applies dynamic mechanical load to human knee joints. Dynamic loading is employed by applying cyclic and periodic force on a target area. The repeated force loading was considered to be an effective modality for repair and rehabilitation of long bones that are subject to ailments like fractures, osteoporosis, osteoarthritis, etc. The proposed device design builds on the knowledge gained in previous animal and mechanical studies. It employs a modified slider-crank linkage mechanism actuated by a brushless Direct Current (DC) motor and provides uniform and cyclic force. The functionality of the device was simulated in a software environment and the structural integrity was analyzed using a finite element method for the prototype construction. The device is controlled by a microcontroller that is programmed to provide the desired loading force at a predetermined frequency and for a specific duration. The device was successfully tested in various experiments for its usability and full functionality. The results reveal that the device works according to the requirements of force magnitude and operational frequency. This device is considered ready to be used for a clinical study to examine whether controlled knee-loading could be an effective regimen for treating the stated bone-related ailments.