The ultimate goal of this research proposal is to develop an injectable cell-polymer composite that will aid in the repair of tissue in osteochondral defects. Based on a novel hydrogel material developed in our laboratory, oligo(poly(ethylene glycol) fumarate), these constructs will be photocrosslinked in situ in the presence of mesenchymal stem cells (MSCs). A three-step approach will be followed to engineer optimal injectable constructs using a combination of cells, biodegradable scaffolds, and spatially and temporally graded release of a growth factor. The first step will be to determine how hydrogel mesh size (distance between crosslinks) affects differentiation of embedded MSCs in vitro and in a rabbit osteochondral defect model. The hydrogel system will then be modified through the synthesis of crosslinking molecules with peptide sequences that are degradable by matrix metalloproteinases found in articular cartilage. The optimal initial mesh size, determined previously, will be used as the basis for study of the effect of different crosslinker concentrations on degradation of the hydrogel due to differentiation of embedded MSCs in vitro and in vivo. Finally, a bilayered construct will be created from the biodegradable hydrogel with the optimal crosslinker concentration in which a gradient of TGF-beta1, released in a controlled manner in response to enzymes produced as neotissue forms, is established to promote cartilage formation in the top half of the construct and bone formation in the lower half. Efficacy of tissue formation from this construct will be tested in vitro and in vivo. The proposed project will provide clinically valuable information regarding new composite constructs for improved repair of osteochondral defects, thus providing a method to generate cartilage repair tissue, which will not degenerate over time, a major limitation with current techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR048756-03
Application #
6881451
Study Section
Special Emphasis Panel (ZRG1-SSS-M (01))
Program Officer
Tyree, Bernadette
Project Start
2003-04-01
Project End
2008-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
3
Fiscal Year
2005
Total Cost
$347,384
Indirect Cost
Name
Rice University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
050299031
City
Houston
State
TX
Country
United States
Zip Code
77005
Lu, Steven; Lee, Esther J; Lam, Johnny et al. (2016) Evaluation of Gelatin Microparticles as Adherent-Substrates for Mesenchymal Stem Cells in a Hydrogel Composite. Ann Biomed Eng 44:1894-907
Lam, Johnny; Clark, Elisa C; Fong, Eliza L S et al. (2016) Evaluation of cell-laden polyelectrolyte hydrogels incorporating poly(L-Lysine) for applications in cartilage tissue engineering. Biomaterials 83:332-46
Lam, Johnny; Clark, Elisa C; Fong, Eliza L S et al. (2016) Data describing the swelling behavior and cytocompatibility of biodegradable polyelectrolyte hydrogels incorporating poly(L-lysine) for applications in cartilage tissue engineering. Data Brief 7:614-9
Lam, Johnny; Lu, Steven; Kasper, F Kurtis et al. (2015) Strategies for controlled delivery of biologics for cartilage repair. Adv Drug Deliv Rev 84:123-34
Madhurakkat Perikamana, Sajeesh Kumar; Lee, Jinkyu; Lee, Yu Bin et al. (2015) Materials from Mussel-Inspired Chemistry for Cell and Tissue Engineering Applications. Biomacromolecules 16:2541-55
Watson, Brendan M; Vo, Tiffany N; Tatara, Alexander M et al. (2015) Biodegradable, phosphate-containing, dual-gelling macromers for cellular delivery in bone tissue engineering. Biomaterials 67:286-96
Trachtenberg, Jordan E; Vo, Tiffany N; Mikos, Antonios G (2015) Pre-clinical characterization of tissue engineering constructs for bone and cartilage regeneration. Ann Biomed Eng 43:681-96
Tatara, Alexander M; Kretlow, James D; Spicer, Patrick P et al. (2015) Autologously generated tissue-engineered bone flaps for reconstruction of large mandibular defects in an ovine model. Tissue Eng Part A 21:1520-8
Lu, Steven; Lam, Johnny; Trachtenberg, Jordan E et al. (2015) Technical Report: Correlation Between the Repair of Cartilage and Subchondral Bone in an Osteochondral Defect Using Bilayered, Biodegradable Hydrogel Composites. Tissue Eng Part C Methods 21:1216-25
Wang, Limin; Lu, Steven; Lam, Johnny et al. (2015) Fabrication of cell-laden macroporous biodegradable hydrogels with tunable porosities and pore sizes. Tissue Eng Part C Methods 21:263-73

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