The clinical utility of tissue engineering depends upon our ability to direct cells to form tissues with characteristic structural and mechanical properties across different hierarchical scales. Ideally, an engineered graft should be autologous and tailored to (re)establish the structure and function of a lost or damaged tissue. Engineered tissues with such a high level of structural and functional complexity would also foster fundamental research by serving as physiologically relevant models for controlled quantitative studies. The application is for tissue engineering of human stratifed grafts suitable for mandibular condyle replacement, a tissue of great clinical interest and an excellent model for studies of stem cell differentiation and functional assembly into craniofacial tissues. We hypothesize that craniofacial structures with physiological gradients of structural and mechanical properties can be grown in vitro by biophysical regulation of adult human stem cells. We thus propose to engineer mandibular tissue grafts by culturing adult human stem cells on specialized scaffolds in advanced bioreactors.
Aim 1 will focus on the development of modular bioreactors with environmental control, interstitial flow, mechanical loading and imaging compatibility.
Aim 2 will focus on the development of silk protein scaffolds with spatial gradients of immobilized growth factors.
In Aim 3, the advanced scaffolds and bioreactors will be utilized to engineer human tissue constructs with structural and mechanical properties resembling those of native condyles. The resulting grafts are expected to have sufficiently high fidelity for use in studies of stem cell responses to genetic and environmental signals and to yield tissue grafts for further studies and eventual application in regenerative medicine. Our overall scientific goal is to obtain new critical information that will improve our understanding of the phenomena and mechanisms involved in human stem cell differentiation during cranio- and orofacial tissue development. The related practical goal is to establish in vitro systems that can be used to study the self-renewal and differentiation of stem cells in a manner predictable of their behavior in vivo, and to custom-design tissue grafts by directed differentiation of human stem cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE016525-03
Application #
7277849
Study Section
Special Emphasis Panel (ZDE1-YL (03))
Program Officer
Lumelsky, Nadya L
Project Start
2005-09-01
Project End
2010-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
3
Fiscal Year
2007
Total Cost
$542,490
Indirect Cost
Name
Columbia University (N.Y.)
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
049179401
City
New York
State
NY
Country
United States
Zip Code
10027
Martín-Moldes, Zaira; Ebrahimi, Davoud; Plowright, Robyn et al. (2018) Intracellular Pathways Involved in Bone Regeneration Triggered by Recombinant Silk-silica Chimeras. Adv Funct Mater 28:
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Ronaldson-Bouchard, Kacey; Vunjak-Novakovic, Gordana (2018) Organs-on-a-Chip: A Fast Track for Engineered Human Tissues in Drug Development. Cell Stem Cell 22:310-324
Ng, Johnathan; Spiller, Kara; Bernhard, Jonathan et al. (2017) Biomimetic Approaches for Bone Tissue Engineering. Tissue Eng Part B Rev 23:480-493
Nims, Robert J; Cigan, Alexander D; Durney, Krista M et al. (2017) * Constrained Cage Culture Improves Engineered Cartilage Functional Properties by Enhancing Collagen Network Stability. Tissue Eng Part A 23:847-858
Rodriguez, María J; Brown, Joseph; Giordano, Jodie et al. (2017) Silk based bioinks for soft tissue reconstruction using 3-dimensional (3D) printing with in vitro and in vivo assessments. Biomaterials 117:105-115
Guo, Jin; Li, Chunmei; Ling, Shengjie et al. (2017) Multiscale design and synthesis of biomimetic gradient protein/biosilica composites for interfacial tissue engineering. Biomaterials 145:44-55
Yuan, Xiaoning; Wei, Yiyong; Villasante, Aránzazu et al. (2017) Stem cell delivery in tissue-specific hydrogel enabled meniscal repair in an orthotopic rat model. Biomaterials 132:59-71
Ng, Johnathan J; Wei, Yiyong; Zhou, Bin et al. (2017) Recapitulation of physiological spatiotemporal signals promotes in vitro formation of phenotypically stable human articular cartilage. Proc Natl Acad Sci U S A 114:2556-2561
Cigan, Alexander D; Nims, Robert J; Vunjak-Novakovic, Gordana et al. (2016) Optimizing nutrient channel spacing and revisiting TGF-beta in large engineered cartilage constructs. J Biomech 49:2089-2094

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