The application's long-term objective is to use a cogent and comprehensive tissue engineering approach to successfully address meniscus regeneration, which remains one of the most elusive problems in musculoskeletal medicine. The study's main hypothesis is that the meniscus can be regenerated by a series of steps that involve the use of a scaffold with bioactive agents, cells, a bioreactor, mechanical stimuli, and an animal model. To test this hypothesis, we propose the following specific aims: 1) To design, fabricate, and characterize meniscus-specific biodegradable scaffolds. 2) To engineer the meniscus. 3) To test the meniscus in an animal model. The methodology involves an analysis and a synthesis phase: In the analysis phase, topographical and spatial properties of the meniscus will be identified using biomechanics, biochemistry, ultrastructural methods, and cell culture. The objective is to define 'gold standard' properties against which the properties of the regenerated meniscus will be compared. In the synthesis phase, fibrochondrocytes will be seeded onto meniscus-specific scaffolds and exposed to mechanical forces. The scaffolds, made of poly(propylene fumarate-co-ethylene glycol), are designed to be bioabsorbable, biocompatible, have mechanical integrity, allow for directed attachment of cells through the use of the GRGD peptide, and provide biosynthetic signals through the use of a growth factor. A hydrodynamic focusing bioreactor, operating in a low-shear environment, will then be used to enhance nutrient transport and to modulate mechanical signals. Furthermore, the effects of hydrostatic pressure and direct compression/tension will also be examined using custom-made instruments. At various time points, the properties of the engineered constructs will be quantified and compared to native tissue properties. The tissue engineered constructs will then be implanted in rabbits to evaluate the in vivo functional characteristics of the new meniscus. The clinical significance of the approach described in this proposal is enormous, since meniscal problems continue to be some of the most vexing in orthopaedics. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR047839-01A2
Application #
6574888
Study Section
Special Emphasis Panel (ZRG1-SSS-M (01))
Program Officer
Panagis, James S
Project Start
2002-12-10
Project End
2007-11-30
Budget Start
2002-12-10
Budget End
2003-11-30
Support Year
1
Fiscal Year
2003
Total Cost
$273,561
Indirect Cost
Name
Rice University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
050299031
City
Houston
State
TX
Country
United States
Zip Code
77005
Huang, Brian J; Huey, Daniel J; Hu, Jerry C et al. (2017) Engineering biomechanically functional neocartilage derived from expanded articular chondrocytes through the manipulation of cell-seeding density and dexamethasone concentration. J Tissue Eng Regen Med 11:2323-2332
Makris, Eleftherios A; Huang, Brian J; Hu, Jerry C et al. (2015) Digoxin and adenosine triphosphate enhance the functional properties of tissue-engineered cartilage. Tissue Eng Part A 21:884-94
Hadidi, Pasha; Yeh, Timothy C; Hu, Jerry C et al. (2015) Critical seeding density improves the properties and translatability of self-assembling anatomically shaped knee menisci. Acta Biomater 11:173-82
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
Higashioka, Michael M; Chen, Justin A; Hu, Jerry C et al. (2014) Building an anisotropic meniscus with zonal variations. Tissue Eng Part A 20:294-302
Huey, Daniel J; Athanasiou, Kyriacos A (2013) Alteration of the fibrocartilaginous nature of scaffoldless constructs formed from leporine meniscus cells and chondrocytes through manipulation of culture and processing conditions. Cells Tissues Organs 197:360-71
Hadidi, Pasha; Athanasiou, Kyriacos A (2013) Enhancing the mechanical properties of engineered tissue through matrix remodeling via the signaling phospholipid lysophosphatidic acid. Biochem Biophys Res Commun 433:133-8
Huey, Daniel J; Hu, Jerry C; Athanasiou, Kyriacos A (2013) Chondrogenically tuned expansion enhances the cartilaginous matrix-forming capabilities of primary, adult, leporine chondrocytes. Cell Transplant 22:331-40
Sanchez-Adams, Johannah; Athanasiou, Kyriacos A (2012) Biomechanics of meniscus cells: regional variation and comparison to articular chondrocytes and ligament cells. Biomech Model Mechanobiol 11:1047-56
Huey, Daniel J; Hu, Jerry C; Athanasiou, Kyriacos A (2012) Unlike bone, cartilage regeneration remains elusive. Science 338:917-21

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