title: Dentin biomodification: strategies, renewable resources and clinical applications.
abstract: OBJECTIVE
  The biomodification of dentin is a biomimetic approach, mediated by bioactive agents, to enhance and reinforce the dentin by locally altering the biochemistry and biomechanical properties. This review provides an overview of key dentin matrix components, targeting effects of biomodification strategies, the chemistry of renewable natural sources, and current research on their potential clinical applications.
  
  
  METHODS
  The PubMed database and collected literature were used as a resource for peer-reviewed articles to highlight the topics of dentin hierarchical structure, biomodification agents, and laboratorial investigations of their clinical applications. In addition, new data is presented on laboratorial methods for the standardization of proanthocyanidin-rich preparations as a renewable source of plant-derived biomodification agents.
  
  
  RESULTS
  Biomodification agents can be categorized as physical methods and chemical agents. Synthetic and naturally occurring chemical strategies present distinctive mechanism of interaction with the tissue. Initially thought to be driven only by inter- or intra-molecular collagen induced non-enzymatic cross-linking, multiple interactions with other dentin components are fundamental for the long-term biomechanics and biostability of the tissue. Oligomeric proanthocyanidins show promising bioactivity, and their chemical complexity requires systematic evaluation of the active compounds to produce a fully standardized intervention material from renewable resource, prior to their detailed clinical evaluation.
  
  
  CONCLUSIONS
  Understanding the hierarchical structure of dentin and the targeting effect of the bioactive compounds will establish their use in both dentin-biomaterials interface and caries management.
authors.affiliation: Department of Restorative Dentistry, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA. Electronic address: bedran@uic.edu.
authors.forename: Ana K
authors.initials: AK
authors.lastname: Bedran-Russo
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Guido F
authors.initials: GF
authors.lastname: Pauli
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Shao-Nong
authors.initials: SN
authors.lastname: Chen
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: James
authors.initials: J
authors.lastname: McAlpine
authors.affiliation: Department of Restorative Dentistry, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA; Department of Biochemistry and Dental Biomaterials, School of Dentistry, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Carina S
authors.initials: CS
authors.lastname: Castellan
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Rasika S
authors.initials: RS
authors.lastname: Phansalkar
authors.affiliation: Department of Restorative Dentistry, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Thaiane R
authors.initials: TR
authors.lastname: Aguiar
authors.affiliation: Department of Restorative Dentistry, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Cristina M P
authors.initials: CM
authors.lastname: Vidal
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: José G
authors.initials: JG
authors.lastname: Napotilano
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Nam
authors.affiliation: Department of Restorative Dentistry, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Ariene A
authors.initials: AA
authors.lastname: Leme
mesh_terms: D003804:Dentin / Q000737:chemistry / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D044945:Proanthocyanidins / Q000737:chemistry / Q000378:metabolism
chemical_list: D044945:Proanthocyanidins
keywords: Biomaterials; Carbodiimide; Collagen cross-linking; Dental caries; Dentin; Proanthocyanidins; Resin–dentin interfaces; Surface biomodification