The overall objective of this proposal is to develop photocrosslinkable hydrogel networks for tissue engineering that elicit desired properties for the repair or replacement of craniofacial cartilage. From a clinical perspective, we hypothesize that the treatment of cartilage defects can be greatly improved by developing injectable polymer-cell constructs that can be reacted upon exposure to light to form well-adhered hydrogels of the exact dimensions and shape of the defect. From a fundamental perspective, we hypothesize that bioinspired hydrogels will provide an improved cell matrix for three-dimensional tissue engineering when the gels are engineered to 1) degrade at a rate that matches tissue formation, 2) incorporate critical cell signals and growth factors, and 3) allow easy structural and chemical modification through photopatterning. In the proposed research plan, we aim to Aim 1: identify and investigate important hydrogel properties that influence the production, composition, and distribution of extracellular matrix in cartilage tissue engineering constructs.
Aim 2 : develop the next generation of hydrogel matrices through advanced photopatterning techniques, to accelerate tissue formation and address critical issues that limit the engineering of thick, three-dimensional cartilaginous tissue.
Aim 3 : examine important clinical issues that are critical to the ultimate repair of structural and craniofacial cartilage deficiencies, namely the integration of tissue engineered and native cartilage, adhesion of in situ formed constructs to native cartilage, and the engineering of complex three-dimensional tissue constructs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE012998-07
Application #
6897511
Study Section
Special Emphasis Panel (ZRG1-SSS-M (01))
Program Officer
Lumelsky, Nadya L
Project Start
1998-09-01
Project End
2007-05-31
Budget Start
2005-06-01
Budget End
2006-05-31
Support Year
7
Fiscal Year
2005
Total Cost
$332,355
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
Zhao, Xing; Papadopoulos, Anestis; Ibusuki, Shinichi et al. (2016) Articular cartilage generation applying PEG-LA-DM/PEGDM copolymer hydrogels. BMC Musculoskelet Disord 17:245
Sridhar, Balaji V; Doyle, Nicholas R; Randolph, Mark A et al. (2014) Covalently tethered TGF-?1 with encapsulated chondrocytes in a PEG hydrogel system enhances extracellular matrix production. J Biomed Mater Res A 102:4464-72
Papadopoulos, Anestis; Bichara, David A; Zhao, Xing et al. (2011) Injectable and photopolymerizable tissue-engineered auricular cartilage using poly(ethylene glycol) dimethacrylate copolymer hydrogels. Tissue Eng Part A 17:161-9
Kloxin, April M; Tibbitt, Mark W; Kasko, Andrea M et al. (2010) Tunable hydrogels for external manipulation of cellular microenvironments through controlled photodegradation. Adv Mater 22:61-6
Lin, Chien-Chi; Anseth, Kristi S (2009) PEG hydrogels for the controlled release of biomolecules in regenerative medicine. Pharm Res 26:631-43
Kloxin, April M; Kasko, Andrea M; Salinas, Chelsea N et al. (2009) Photodegradable hydrogels for dynamic tuning of physical and chemical properties. Science 324:59-63
Salinas, Chelsea N; Anseth, Kristi S (2009) Decorin moieties tethered into PEG networks induce chondrogenesis of human mesenchymal stem cells. J Biomed Mater Res A 90:456-64
Salinas, C N; Anseth, K S (2009) Mesenchymal stem cells for craniofacial tissue regeneration: designing hydrogel delivery vehicles. J Dent Res 88:681-92
Fairbanks, Benjamin D; Schwartz, Michael P; Bowman, Christopher N et al. (2009) Photoinitiated polymerization of PEG-diacrylate with lithium phenyl-2,4,6-trimethylbenzoylphosphinate: polymerization rate and cytocompatibility. Biomaterials 30:6702-7
Rydholm, Amber E; Held, Nicole L; Benoit, Danielle S W et al. (2008) Modifying network chemistry in thiol-acrylate photopolymers through postpolymerization functionalization to control cell-material interactions. J Biomed Mater Res A 86:23-30

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