This career transition award will provide the candidate with the opportunity to investigate new areas of research: mechanotransduction and mechanical stimulation for regenerating condylar cartilage of the temporomandibular joint (TMJ). The environment in the Dept. of Chemical and Biological Eng. at the University of Colorado and the School of Dentistry at the Health Science Center will provide the candidate with fruitful collaborations, mentorship and a plethora of shared equipment. The long-term goals of the candidate are (i) to develop a successful research career in tissue engineering, (ii) to make a substantial advancement in developing tissue engineering strategies for treating patients with TMJ disorders, and (iii) to provide a positive learning environment for the next generation of researchers and tissue engineers. The overall objective of this proposal is to stimulate the regeneration of cartilage through mechanical conditioning of tissue engineering scaffolds for the replacement of condylar cartilage of the TMJ. The global hypothesis of this research is photopolymerized gels can be designed with high fidelity to provide insight into the mechanotransduction pathways of chondrocytes, and this knowledge can then be used to engineer gel environments that when subjected to mechanical conditioning will promote functional tissue development. Specifically, the aims of this research are to:
Aim 1 : Elucidate the chondrocyte's response (cell proliferation and ECM synthesis) to a range of loading conditions as a function of gel material properties and chemistries;
Aim 2 : Isolate and study the mechanotransduction pathways in chondrocytes that involve nitric oxide and intracellular calcium and their potential role in the cell's response to changes in cell deformation and streaming potentials and to the presence of cell-ECM interactions.
Aim 3 : Incorporate degradable crosslinks into the hydrogels and examine the macroscopic tissue composition and mechanical properties as a function of loading regimes and degradation profiles.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Career Transition Award (K22)
Project #
5K22DE016608-04
Application #
7480963
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Hardwick, Kevin S
Project Start
2005-09-06
Project End
2010-08-31
Budget Start
2008-09-01
Budget End
2010-08-31
Support Year
4
Fiscal Year
2008
Total Cost
$135,000
Indirect Cost
Name
University of Colorado at Boulder
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
007431505
City
Boulder
State
CO
Country
United States
Zip Code
80309
Swartzlander, Mark D; Blakney, Anna K; Amer, Luke D et al. (2015) Immunomodulation by mesenchymal stem cells combats the foreign body response to cell-laden synthetic hydrogels. Biomaterials 41:79-88
Blakney, Anna K; Swartzlander, Mark D; Bryant, Stephanie J (2012) The effects of substrate stiffness on the in vitro activation of macrophages and in vivo host response to poly(ethylene glycol)-based hydrogels. J Biomed Mater Res A 100:1375-86
Vernerey, Franck J; Greenwald, Eric C; Bryant, Stephanie J (2012) Triphasic mixture model of cell-mediated enzymatic degradation of hydrogels. Comput Methods Biomech Biomed Engin 15:1197-210
Roberts, Justine J; Nicodemus, Garret D; Greenwald, Eric C et al. (2011) Degradation improves tissue formation in (un)loaded chondrocyte-laden hydrogels. Clin Orthop Relat Res 469:2725-34
Steinmetz, Neven J; Bryant, Stephanie J (2011) The effects of intermittent dynamic loading on chondrogenic and osteogenic differentiation of human marrow stromal cells encapsulated in RGD-modified poly(ethylene glycol) hydrogels. Acta Biomater 7:3829-40
Nicodemus, G D; Skaalure, S C; Bryant, S J (2011) Gel structure has an impact on pericellular and extracellular matrix deposition, which subsequently alters metabolic activities in chondrocyte-laden PEG hydrogels. Acta Biomater 7:492-504
Roberts, Justine J; Earnshaw, Audrey; Ferguson, Virginia L et al. (2011) Comparative study of the viscoelastic mechanical behavior of agarose and poly(ethylene glycol) hydrogels. J Biomed Mater Res B Appl Biomater 99:158-69
Roberts, Justine J; Nicodemus, Garret D; Giunta, Suzanne et al. (2011) Incorporation of biomimetic matrix molecules in PEG hydrogels enhances matrix deposition and reduces load-induced loss of chondrocyte-secreted matrix. J Biomed Mater Res A 97:281-91
Villanueva, Idalis; Gladem, Sara K; Kessler, Jeff et al. (2010) Dynamic loading stimulates chondrocyte biosynthesis when encapsulated in charged hydrogels prepared from poly(ethylene glycol) and chondroitin sulfate. Matrix Biol 29:51-62
Nicodemus, G D; Bryant, S J (2010) Mechanical loading regimes affect the anabolic and catabolic activities by chondrocytes encapsulated in PEG hydrogels. Osteoarthritis Cartilage 18:126-37

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