Current trends in conservative and minimally invasive dentistry (MID) emphasize the reversal and repair of the active caries process as a first step to restoring the diseased tissue. Enamel remineralization is an accepted phenomenon with established mechanisms, but dentin remineralization strategies are at an early stage of development. Results from the prior period have shown substantial recovery of the hydrated carious tissues mechanical properties, which we have termed functional remineralization. If functional remineralization can be clinically achieved, it would become a key strategy in MID with the eventual outcome of improved oral health care and lower costs. In support of this goal, , new knowledge on basic biomineralization mechanisms has emerged, and has inspired new approaches that achieve appropriate remineralization within collagen fibrils (intrafibrillar) and between the fibrils (extrafibrillar) to improve the functional remineralization of carious dentin structures. We propose to continue the UCSF-Univ. of Florida collaboration established in the prior period, which will include:
Aim 1 a) enhancing the polymer-induced liquid-precursor (PILP) process that has successfully mineralized a variety of collagen matrices, and shown significant functional remineralization of artificial caries lesions. b) extending PILP by potential synergisti approaches including other polyanionic polymers and constant composition methods. c) studying the structure of carious dentin zones to determine their role in limitations of the remineralization process. d) defining microstructural variations in normal and functionally remineralized dentin.
Aim 2 evaluates dentin collagen mineralization in model systems including mouse models that lack critical non-collagenous proteins to gain insight into mineralization mechanisms of the collagen scaffold.
Aim 3 a) applies the improvements from Aims 1 and insights from Aim 2 to applications in two in vitro models of natural human caries that progressively move towards clinical application.
Aim 4 establishes that functional remineralization as indicated by AFM-based nanoindentation testing of hydrated tissue also reflects properties at clinically relevant sizes by use of 4-point bending tests combined with Micro X- ray Computed Tomography. To carry out this work we have established a talented team of SF Bay area investigators from UCSF, LBNL and SSRL, as well as our Florida collaborators who developed the PILP process. The proposed studies will build on our progress and translate the emerging understanding of mechanisms in biomineralization so that we can optimize remineralization kinetics and restoration of dentin caries and move toward a clinically relevant delivery system. Establishing methods to functionally remineralize dentin caries thereby restoring the mechanical properties of the hydrated tissue will minimize conventional restorative treatment and maximize conservation of tooth structure.

Public Health Relevance

Dental caries (tooth decay) is the most common infectious disease and untreated disease ranges from about 20% in children 2-5 years to 26% in adults age 20-64 (http://www.cdc.gov/nchs/FASTATS/dental.htm). Although enamel caries may be remineralized in its early stages, once caries has reached the dentin, the tissue that forms the bulk of the tooth, standard conservative treatments require restoration (drill and fill). This projct develops methods to functionally remineralize dentin caries, restoring the mechanical properties of the hydrated tissue and thereby minimizing conventional restorative treatment and maximizing conservation of tooth structure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
4R01DE016849-10
Application #
9093577
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Wan, Jason
Project Start
2005-07-01
Project End
2017-06-30
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
10
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Dentistry
Type
Schools of Dentistry/Oral Hygn
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
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Chien, Yung-Ching; Tao, Jinhui; Saeki, Kuniko et al. (2017) Using biomimetic polymers in place of noncollagenous proteins to achieve functional remineralization of dentin tissues. ACS Biomater Sci Eng 3:3469-3479
Saeki, K; Chien, Y-C; Nonomura, G et al. (2017) Recovery after PILP remineralization of dentin lesions created with two cariogenic acids. Arch Oral Biol 82:194-202
Nurrohman, H; Saeki, K; Carneiro, K et al. (2016) Repair of dentin defects from DSPP knockout mice by PILP mineralization. J Mater Res 31:321-327
Chien, Y-C; Burwell, A K; Saeki, K et al. (2016) Distinct decalcification process of dentin by different cariogenic organic acids: Kinetics, ultrastructure and mechanical properties. Arch Oral Biol 63:93-105
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Burwell, Anora K; Thula-Mata, Taili; Gower, Laurie B et al. (2012) Functional remineralization of dentin lesions using polymer-induced liquid-precursor process. PLoS One 7:e38852
Thula, Taili T; Rodriguez, Douglas E; Lee, Myong Hwa et al. (2011) In vitro mineralization of dense collagen substrates: a biomimetic approach toward the development of bone-graft materials. Acta Biomater 7:3158-69

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