Engineering of bone, cartilage, and osteochondral tissue offers promising alternative approaches for regenerative medicine as well as tools to study skeletal tissue developmental processes and disease models. To understand the electrotherapeutic factors and advance healing of musculoskeletal tissues, one needs to develop modalities for non-invasive, quantitative, multiscale imaging of the forming tissues. To date, there has not been a bioreactor system that allows real-time monitoring of clinically sized engineered tissues without sacrificing the samples or interfering with the cultivating condition, principally due to the size and portability of the culture system, and the fact that imaging systems are usually located in a separate facility. We propose to develop a new bioreactor system, which incorporates non-destructive imaging techniques to monitor bone, cartilage, and osteochondral tissue development in vitro. Our goal is to integrate separate efforts of two laboratories specializing in tissue engineering and radiological imaging toward the development of a portable, imaging- compatible bioreactor enabling quantitative on-line studies of complex cartilage/bone tissue constructs. We will rigorously test this hypothesis by studying bone formation by endochondral and intramembraneous ossification on a microscopic to macroscopic level.
Three specific aims will be pursued: (a) Development of a portable bioreactor integrated with imaging, (b) ?CT bioreactor studies of cartilage/bone formation, and (c) ?-PIXE bioreactor studies of cartilage/bone formation. The anticipated scientific impact will be in significant new insights into bone formation through the development of non-invasive quantitative imaging at multiple scales.

Public Health Relevance

Radically new approaches are necessary for advancing real-time insights into the progression of cartilage/bone formation. The proposed studies are designed to complement the goals of NIAMS, which include promoting research towards improved understanding of the factors and mechanisms involved in skeletal development, regeneration and disease. The project findings will result in new scientific data for bone formation, which can be translated into the development of novel electrotherapeutic devices for potential application in a range of regenerative medicine scenarios.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Special Emphasis Panel (ZAR1-KM (M1))
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Wang, Fei
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Tufts University
Engineering (All Types)
Schools of Engineering
United States
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Bernhard, Jonathan C; Vunjak-Novakovic, Gordana (2016) Should we use cells, biomaterials, or tissue engineering for cartilage regeneration? Stem Cell Res Ther 7:56
Çakmak, Anıl S; Çakmak, Soner; White, James D et al. (2016) Synergistic effect of exogeneous and endogeneous electrostimulation on osteogenic differentiation of human mesenchymal stem cells seeded on silk scaffolds. J Orthop Res 34:581-90
Pai, Vaibhav P; Martyniuk, Christopher J; Echeverri, Karen et al. (2016) Genome-wide analysis reveals conserved transcriptional responses downstream of resting potential change in Xenopus embryos, axolotl regeneration, and human mesenchymal cell differentiation. Regeneration (Oxf) 3:3-25
Ng, Johnathan; Wei, Yiyong; Zhou, Bin et al. (2016) Extracellular matrix components and culture regimen selectively regulate cartilage formation by self-assembling human mesenchymal stem cells in vitro and in vivo. Stem Cell Res Ther 7:183
Li, Chunmei; Levin, Michael; Kaplan, David L (2016) Bioelectric modulation of macrophage polarization. Sci Rep 6:21044
Wobma, Holly; Vunjak-Novakovic, Gordana (2016) Tissue Engineering and Regenerative Medicine 2015: A Year in Review. Tissue Eng Part B Rev 22:101-13
Lobikin, Maria; Paré, Jean-François; Kaplan, David L et al. (2015) Selective depolarization of transmembrane potential alters muscle patterning and muscle cell localization in Xenopus laevis embryos. Int J Dev Biol 59:303-11
White, James D; Wang, Siran; Weiss, Anthony S et al. (2015) Silk-tropoelastin protein films for nerve guidance. Acta Biomater 14:1-10
Spiller, Kara L; Freytes, Donald O; Vunjak-Novakovic, Gordana (2015) Macrophages modulate engineered human tissues for enhanced vascularization and healing. Ann Biomed Eng 43:616-27
Yodmuang, Supansa; McNamara, Stephanie L; Nover, Adam B et al. (2015) Silk microfiber-reinforced silk hydrogel composites for functional cartilage tissue repair. Acta Biomater 11:27-36

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