This application proposes to develop molecularly designed peptide nanostructures that can trigger differentiation of progenitor cells and mineralization in physiological media with features that mimic enamel or bone matrices. The proposed research is based on the hypothesis that regeneration of enamel and bone can be triggered by templates designed at the nanoscale to present biological signals and induce biomimetic mineralization. Using in vitro assays, we will investigate how these biomimetic mineralization templates affect matrix synthesis by ameloblasts and osteoprogenitor cells, and also test their performance in embryonic tooth culture and in vivo bone repair models. This research will guide the development of synthetic, versatile, nanostructured templates that can be used for hard tissue (enamel or bone) regeneration and repair without the need for autologous or autogenic tissue transplantation. The proposed program's specific aims include: development of peptide amphiphiles that will self-assemble in physiological fluids and trigger biomimetic mineralization of enamel- or bone-like matrices, testing of these nanofiber systems in vitro with osteoprogenitor and ameloblast cells using mineralization, protein and gene expression assays, and using patterned substrates or scaffolds of peptide amphiphile nanofibers for in vitro and in vivo regeneration of dental and bone tissues in murine models. The proposed research program is a collaborative effort of four investigators specializing in self-assembly/materials chemistry, dental tissue biology and orthopedic surgery, whose interests intersect on the focused application of nanoscience and nanotechnology to biomedical research.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
1R01DE015920-01A1
Application #
6941913
Study Section
Special Emphasis Panel (ZRG1-BPC-R (50))
Program Officer
Lumelsky, Nadya L
Project Start
2005-07-12
Project End
2010-06-30
Budget Start
2005-07-12
Budget End
2006-06-30
Support Year
1
Fiscal Year
2005
Total Cost
$637,472
Indirect Cost
Name
Northwestern University at Chicago
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
160079455
City
Evanston
State
IL
Country
United States
Zip Code
60201
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Lee, Sungsoo S; Fyrner, Timmy; Chen, Feng et al. (2017) Sulfated glycopeptide nanostructures for multipotent protein activation. Nat Nanotechnol 12:821-829
Hendricks, Mark P; Sato, Kohei; Palmer, Liam C et al. (2017) Supramolecular Assembly of Peptide Amphiphiles. Acc Chem Res 50:2440-2448
Yin, Kaifeng; Lin, Wenting; Guo, Jing et al. (2017) MiR-153 Regulates Amelogenesis by Targeting Endocytotic and Endosomal/lysosomal Pathways-Novel Insight into the Origins of Enamel Pathologies. Sci Rep 7:44118
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Pazos, Elena; Sleep, Eduard; Rubert Pérez, Charles M et al. (2016) Nucleation and Growth of Ordered Arrays of Silver Nanoparticles on Peptide Nanofibers: Hybrid Nanostructures with Antimicrobial Properties. J Am Chem Soc 138:5507-10
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Preslar, Adam T; Tantakitti, Faifan; Park, Kitae et al. (2016) (19)F Magnetic Resonance Imaging Signals from Peptide Amphiphile Nanostructures Are Strongly Affected by Their Shape. ACS Nano 10:7376-84

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