The application's long-term objective is to use a comprehensive tissue reconstruction approach to successfully address regeneration of the temporomandibular joint (TMJ) disc. There is a clear need to regenerate the TMJ disc to alleviate the need for discectomy in severe cases of disc displacement. Seventy percent of patients with temporomandibular disorders suffer from disc displacement, which can result in disc degeneration and/or perforation and can be manifested in jaw clicking, locking and severe pain. The chief hypothesis of our study is that we can regenerate a TMJ disc construct comparable to the native disc by the use of a peptide-modified, biodegradable scaffold with the appropriate combination of growth factors, cells and mechanical stimuli with enhanced diffusion. To test this hypothesis, we propose the following specific aims: 1) To characterize the TMJ disc at the tissue level, 2) to describe the TMJ disc at the cellular level and 3) to engineer the TMJ disc in vitro. This comprehensive study will lay the groundwork for future in vivo studies to replace damaged TMJ discs where implants have failed. Furthermore, since the TMJ disc is a poorly understood tissue, collectively the proposed studies will provide broad and detailed knowledge of structure-function properties of the normal TMJ disc. This vital information will allow the definition of design and validation criteria to engineer disc constructs. To characterize the disc at the tissue level, native porcine TMJ discs will be examined to determine ultrastructure, biomechanical properties under tension and compression, and biochemical content and organization. To describe the disc at the cellular level, cellular topography will be elucidated, subpopulations will be identified, and cells will be cultured on two dimensional poly(propylene fumarate-co-ethylene glycol)-GRGD surfaces where proliferation and biosynthesis will be measured with varied growth factors present. Once the native disc is characterized, an engineered disc will be created using the optimal growth factors incorporated within the scaffold in the shape of a native disc, using a combination of a rotating bioreactor, intermittent hydrostatic pressure and direct compression/tension. At various time points, properties of the engineered constructs will be compared to the determined native disc properties. The proposed research represents a novel approach to regenerate the TMJ disc in that we intend to first perform the necessary characterization studies and then use cell-seeded scaffolds, bioactive factors, mechanical signals and enhanced diffusion to facilitate disc regeneration.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE015038-05
Application #
7469456
Study Section
Special Emphasis Panel (ZRG1-SSS-M (01))
Program Officer
Lumelsky, Nadya L
Project Start
2004-07-01
Project End
2010-06-30
Budget Start
2008-07-01
Budget End
2010-06-30
Support Year
5
Fiscal Year
2008
Total Cost
$272,354
Indirect Cost
Name
Rice University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
050299031
City
Houston
State
TX
Country
United States
Zip Code
77005
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Vapniarsky, Natalia; Huwe, Le W; Arzi, Boaz et al. (2018) Tissue engineering toward temporomandibular joint disc regeneration. Sci Transl Med 10:
Cissell, Derek D; Link, Jarrett M; Hu, Jerry C et al. (2017) A Modified Hydroxyproline Assay Based on Hydrochloric Acid in Ehrlich's Solution Accurately Measures Tissue Collagen Content. Tissue Eng Part C Methods 23:243-250
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Vapniarsky, Natalia; Aryaei, Ashkan; Arzi, Boaz et al. (2017) The Yucatan Minipig Temporomandibular Joint Disc Structure-Function Relationships Support Its Suitability for Human Comparative Studies. Tissue Eng Part C Methods 23:700-709
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Lee, Jennifer K; Responte, Donald J; Cissell, Derek D et al. (2014) Clinical translation of stem cells: insight for cartilage therapies. Crit Rev Biotechnol 34:89-100
Murphy, M K; Arzi, B; Hu, J C et al. (2013) Tensile characterization of porcine temporomandibular joint disc attachments. J Dent Res 92:753-8

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