The overall purpose of the NIH Pathway to Independence Award K99/ROO application is to provide a year of support for the mentored phase that is crucial in completing the critical testing of four hypotheses, followed by manuscript submission to relevant journals. The subsequent 3 year independent phase is necessary to establish my research program and reaching my goals as a junior faculty member. It would enable me to establish myself as an independent investigator in biomaterials integration and characterization taking into account both human and comparable animal tissues, subsequently building tissues with well optimized bioengineered interfaces. This award will enable me to study the proposed specific aims defined in this proposal and expand my knowledge on building the next generation materials for tissue regeneration. The thrust of these efforts is based on a general hypothesis that the functional biomechanics of a tooth are derived from structural and chemical interactions of its different components at several hierarchical levels (macro-, micro- and nano-scales), and that these yield properties that depend on location, age, and gender. Destruction of tissues including the periodontal ligament (PDL), cementum, and bone can cause loss of teeth due to periodontitis. Key challenges include 1). Understanding degradation of the tissues associated with disease progression, and 2). Regeneration of the interfaces that bind the oral tissues together. To address the first challenge, an animal model for periodontitis will be developed and the sequential degeneration of tissues determined by studying their structure, chemical composition and mechanical properties. For the second challenge, tissue engineering (TE) can be used to create novel scaffolds. However, a major limitation of current TE procedures is limited knowledge of scaffold biomechanics. An efficient scaffold should sustain functional loads in addition to providing an environment conducive to desired cell behavior. To address these challenges, the inherent characteristics of the tissues and their interfaces must be determined. Then, they can be mimicked using TE to create appropriate scaffolds. Hence the following specific aims are defined to: 1). Investigate structure, chemical composition, mechanical properties of primary and secondary cementums, 2). Investigate structure, chemical composition, mechanical properties of cementum and its interface with root dentin, 3). Investigate strain fields using functional loads on anterior and posterior teeth as a function of age, 4). Perform a comparison studies between structure, chemical composition and mechanical properties of healthy human and rat alveolar bone, PDL, cementum, root dentin and their bimaterial interfaces. This information will be used to determine chronological changes in structure, chemical composition and mechanical properties in the rat periodontal tissues and their bimaterial interfaces during disease progression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Transition Award (R00)
Project #
5R00DE018212-04
Application #
7851450
Study Section
Special Emphasis Panel (NSS)
Program Officer
Drummond, James
Project Start
2008-07-01
Project End
2012-06-30
Budget Start
2010-07-01
Budget End
2012-06-30
Support Year
4
Fiscal Year
2010
Total Cost
$247,420
Indirect Cost
Name
University of California San Francisco
Department
Dentistry
Type
Schools of Dentistry
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Lin, Jeremy D; Jang, Andrew T; Kurylo, Michael P et al. (2017) Periodontal ligament entheses and their adaptive role in the context of dentoalveolar joint function. Dent Mater 33:650-666
Kurylo, Michael P; Grandfield, Kathryn; Marshall, Grayson W et al. (2016) Effect of proteoglycans at interfaces as related to location, architecture, and mechanical cues. Arch Oral Biol 63:82-92
Djomehri, Sabra I; Candell, Susan; Case, Thomas et al. (2015) Mineral density volume gradients in normal and diseased human tissues. PLoS One 10:e0121611
Grandfield, Kathryn; Herber, Ralf Peter; Chen, Ling et al. (2015) Strain-guided mineralization in the bone-PDL-cementum complex of a rat periodontium. Bone Rep 3:20-31
Jang, Andrew T; Merkle, Arno P; Fahey, Kevin P et al. (2015) Multiscale biomechanical responses of adapted bone-periodontal ligament-tooth fibrous joints. Bone 81:196-207
Lin, Jeremy D; Lee, Jihyun; Ozcoban, Hüseyin et al. (2014) Biomechanical adaptation of the bone-periodontal ligament (PDL)-tooth fibrous joint as a consequence of disease. J Biomech 47:2102-14
Jang, Andrew T; Lin, Jeremy D; Choi, Ryan M et al. (2014) Adaptive properties of human cementum and cementum dentin junction with age. J Mech Behav Biomed Mater 39:184-96
Grandfield, Kathryn; Chattah, Netta Lev-Tov; Djomehri, Sabra et al. (2014) The narwhal (Monodon monoceros) cementum-dentin junction: a functionally graded biointerphase. Proc Inst Mech Eng H 228:754-67
Jang, Andrew T; Lin, Jeremy D; Seo, Youngho et al. (2014) In situ compressive loading and correlative noninvasive imaging of the bone-periodontal ligament-tooth fibrous joint. J Vis Exp :
Ho, Sunita P; Kurylo, Michael P; Grandfield, Kathryn et al. (2013) The plastic nature of the human bone-periodontal ligament-tooth fibrous joint. Bone 57:455-67

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