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 #
5R01DE016849-07
Application #
8525385
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Wan, Jason
Project Start
2005-07-01
Project End
2017-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
7
Fiscal Year
2013
Total Cost
$469,636
Indirect Cost
$134,380
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
Thompson, V P; Watson, T F; Marshall Jr, G W et al. (2013) Outside-the-(cavity-prep)-box thinking. Adv Dent Res 25:24-32
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
Bertassoni, Luiz E; Habelitz, Stefan; Marshall, Sally J et al. (2011) Mechanical recovery of dentin following remineralization in vitro--an indentation study. J Biomech 44:176-81
Thula, Taili T; Svedlund, Felicia; Rodriguez, Douglas E et al. (2011) Mimicking the Nanostructure of Bone: Comparison of Polymeric Process-Directing Agents. Polymers (Basel) 3:10-35
Bertassoni, Luiz Eduardo; Habelitz, Stefan; Pugach, Megan et al. (2010) Evaluation of surface structural and mechanical changes following remineralization of dentin. Scanning 32:312-9
Bertassoni, L E; Habelitz, S; Kinney, J H et al. (2009) Biomechanical perspective on the remineralization of dentin. Caries Res 43:70-7
Rodriguez, Brian J; Jesse, Stephen; Habelitz, Stefan et al. (2009) Intermittent contact mode piezoresponse force microscopy in a liquid environment. Nanotechnology 20:195701
Pugach, M K; Strother, J; Darling, C L et al. (2009) Dentin caries zones: mineral, structure, and properties. J Dent Res 88:71-6
Bertassoni, L E; Marshall, G W (2009) Papain-gel degrades intact nonmineralized type I collagen fibrils. Scanning 31:253-8
Hsu, Kuang-Wei; Marshall, Sally J; Pinzon, Lilliam M et al. (2008) SEM evaluation of resin-carious dentin interfaces formed by two dentin adhesive systems. Dent Mater 24:880-7

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