Modulation of acquired enamel pellicle to control dental mineral loss: unravelling mechanisms to make therapies possible

• Grant number: 19/26070-1
• Support Opportunities: Research Projects - Thematic Grants
• Start date: February 01, 2021
• End date: January 31, 2026
• Field of knowledge: Health Sciences - Dentistry - Social and Preventive Dentistry
• Principal Investigator: Marília Afonso Rabelo Buzalaf
• Grantee: Marília Afonso Rabelo Buzalaf
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil
• Pesquisadores principais: Ana Carolina Magalhães ; Flavio Henrique da Silva
• Associated researchers: Anuradha Prakki ; Cristiane de Almeida Baldini Cardoso ; Daniela Rios Honório ; Heitor Marques Honório ; Jonas de Almeida Rodrigues ; Juliano Pelim Pessan ; Karina Midori Mori Carneiro ; Marcela Charantola Rodrigues ; Paulo Augusto Netz ; Reinaldo Marchetto ; Thiago Cruvinel da Silva
• Associated research grant(s): 23/01357-1 - Effect of a new cystatin derived from "Maqui Berry" on acquired pellicle thickness and viscoelastic properties, as well as early colonizers, microcosm biofilm profile and viability, and prevention of enamel demineralization, AP.R; 21/03389-2 - Multi-user equipment approved in grant 19/26070-1: Quartz Crystal Microbalance with Dissipation Monitoring, AP.EMU
• Associated scholarship(s): 24/20780-5 - Development of a new recombinant protein to protect against tooth demineralization and evaluation of the expression system in Pichia pastoris yeast, BP.DR; 24/20622-0 - In Vitro and In Vivo Evaluation of a New Hydrogel Containing Association Between Lipidic Nanoparticles Containing Vitamin E and Hybrid Recombinant Protein for Protection Against Erosive Demineralization, BP.MS; 24/22199-8 - Effect of a combination of proteins/peptide on the acquired pellicle engineering, including a new cystatin derived from Maqui Berry (MaquiCPI-3), Stn15pSpS, and Hemoglobin, associated with EGCG, for protection against dental erosion in vitro, BP.IC; + associated scholarships 23/17757-9 - In Vitro and In Vivo Evaluation of a New Hydrogel Containing a Combination of Recombinant Protein with Vitamin E for Protection Against Erosive Demineralization, BP.MS; 24/15179-0 - Acquired enamel pellicle and dental biofilm engineering with CaneStat, an innovative hybrid protein: a new strategy for the control of dental caries, BP.PD; 23/16774-7 - Modulation of acquired pellicle and dental biofilm for control of dental mineral loss: use of an innovative gel with caneCPI-5 associated with vitamin e, BP.PD; 24/09851-8 - Evaluation of the Effect of a New Recombinant Hybrid Protein (CANEStat) on the Proteomic Profile of the Acquired Enamel Pellicle and Dental Erosion, BP.IC; 24/09669-5 - Evaluation of the protective potential of CaneCPI-5, with or without fluoride, in preventing demineralization and in remineralizing artificial carious lesions: an in situ study, BP.PD; 23/14457-4 - In vitro evaluation of the protective potential of the association of statherin derived peptide with different concentrations of sodium trimethaphosphate against intrinsic initial dental erosion, BP.IC; 23/14691-7 - Evaluation of mouthwashes containing organic components (CaneCPI-5, MaquiCPI-3, Estatherin and Hemoglobin) in acquired pellicle engineering for the control of dental erosion in vivo, BP.IC; 23/11617-0 - Acquired pellicle engineering: in vitro evaluation of the protective potential of a recombinant hybrid protein against initial erosion, BP.IC; 23/11487-0 - Analysis of the protective effect of different proteins/peptides (CaneCPI-5, MaquiCPI-3, Statherin and Hemoglobin) added in orodispersible films for the prevention of initial dental erosion in vivo, BP.IC; 22/11297-3 - Acquired pellicle engineering for the control of dental erosion: in vitro evaluation of the protective potential of different concentrations of sodium trimetaphosphate associated or not with CaneCPI-5, BP.IC; 21/14161-2 - Recombinant production and functional evaluation of a hybrid recombinant protein with potential to interact with hydroxyapatite to protect against dental caries and erosion, BP.DD; 22/13268-0 - Evaluation of the protective potential of CaneCPI-5, Stn15pSpS or Hb, alone or in combination against erosive challenges in vivo: comparison between mouthwash solutions and orodispersible films, BP.PD; 22/02424-1 - Proteomic analysis of acquired enamel pellicle in vivo and saliva under the circadian cycle effect, BP.IC; 21/03497-0 - Engineering of acquired enamel film to protect against erosive dental wear: evaluation of the protective effect of cystatin derived from sugarcane (CaneCPI-5), hemoglobin and/or peptide derived from staterine, associated or not with EGCG, BP.DR; 20/13351-0 - Resveratrol for prevention of dental caries and erosion: in vitro studies, BP.MS; 21/09164-2 - Heterologous expression and purification of CaneCPI-5, BP.TT; 21/02958-3 - Construction and validation of more efficient plasmids for the production of recombinant proteins in Escherichia coli, BP.IC; 21/00203-5 - Effect of saliva enrichment with CaneCPI-5, Stn15pSpS or hemoglobin, isolated or combined, associated or not with EGCG, in thickness, viscoelastic properties, interfacial load and morphology of the acquired enamel pellicle, BP.PD; 21/03098-8 - Evaluation of the effect of different concentrations of a peptide derived from statherin (Stn15pSpS) on the viability of microcosm biofilm and on the prevention of enamel demineralization, BP.IC - associated scholarships

Abstract

The presence of the acquired enamel pellicle (AEP) is one of the protective factors against erosive tooth wear (ETW) and dental caries. Among the AEP proteins with enamel binding potential and acid-resistant properties, cystatin, hemoglobin (Hb) and statherin have been recently identified by our group. Modification of the protein profile of the AEP by the incorporation of some proteins can interfere in the initial bacterial colonization of the biofilm, changing its structure. Therefore, the modification of the AEP can be promising not only for the control of ETW, but also for the control of dental caries, which has been little studied. Thus, in the present proposal, focused on "acquired pellicle engineering", we intend to evaluate the impact of modification of this integument with proteins that bind to enamel and that have acid-resistant properties (cystatin, Hb, statherin and combination thereof) on the proteomic profile of the AEP formed in vivo, as well as on its protective potential against extrinsic and intrinsic erosive challenges. The combination of these proteins with other actives such as trimetaphosphate (TMP) and epigallo cathechin gallate (EGCG), which may enhance their binding to the AEP, will also be evaluated, as well as the possible mechanisms underlying this protective potential. Considering that the formation of the dental biofilm occurs by the attachment of bacterial surface adhesins to AEP proteins with complementary receptors, the modification in the protein composition of this integument due to the enrichment with acid-resistant proteins will certainly have an impact on the initial microbial colonization of the AEP, changing its entire structure, which will also be evaluated, using a microcosm biofilm model. Finally, different vehicles for the use of these proteins will be evaluated, so that a product can be elaborated that can be clinically tested for the control of caries and ETW. These steps are crucial for developing a product based on one or a combination of these proteins that will be widely used as a new approach to control ETW dental caries, based on procedures for "acquired pellicle engineering". (AU)

Scientific publications

(16)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ARAUJO, TAMARA TEODORO; CAMILOTI, GABRIEL DOMINGUES; VALLE, ALINE DIONIZIO; SILVA, NATARA DIAS GOMES; SOUZA, BEATRIZ MARTINES; CARVALHO, THAMYRIS DE SOUZA; CAMARA, JOAO VICTOR FRAZAO; SHIBAO, PRISCILA YUMI TANAKA; HENRIQUE-SILVA, FLAVIO; CRUVINEL, THIAGO; et al. A sugarcane cystatin (CaneCPI-5) alters microcosm biofilm formation and reduces dental caries. BIOFOULING, v. 37, n. 1, p. 109-116, JAN 28 2021. (19/26070-1, 19/08032-5)

ARAUJO, TAMARA TEODORO; CARVALHO, THAMYRIS SOUZA; DIONIZIO, ALINE; BOGAZ DEBORTOLLI, ANA LUIZA; OLIVEIRA VENTURA, TALITA MENDES; SOUZA, BEATRIZ MARTINES; VILAS BOAS FEITOSA, CHELSEA MARIA; PEREIRA BARBOSA, HELOISA APARECIDA; DA SILVA RIBEIRO, CAROLINE FERNANDA; MARTINI, TATIANA; et al. rotein-based engineering of the initial acquired enamel pellicle in vivo: Proteomic evaluatio. Journal of Dentistry, v. 116, JAN 2022. (19/19002-0, 18/12041-7, 19/08032-5, 19/26070-1)

CARVALHO, THAMYRIS SOUZA; ARAUJO, TAMARA TEODORO; VENTURA, TALITA MENDES OLIVEIRA; DIONIZIO, ALINE; CAMARA, JOAO VICTOR FRAZAO; MORAES, SAMANTA MASCARENHAS; LEME, JULIA CHAPARRO; GRIZZO, LARISSA TERCILIA; CRUSCA, EDSON; SHIBAO, PRISCILA YUMI TANAKA; et al. Hemoglobin Protects Enamel against Intrinsic Enamel Erosive Demineralization. Caries Research, v. 58, n. 2, p. 18-pg., 2024-04-01. (19/26070-1, 19/16254-8)

TAIRA, EVEN AKEMI; FERRARI, CAROLINA RUIS; CARVALHO, GABRIEL; PELA, VINICIUS TAIOQUI; VENTURA, TALITA MENDES OLIVEIRA; CRUSCA, EDSON; MARCHETTO, REINALDO; BUZALAF, MARILIA AFONSO RABELO. Statherin-Derived Peptide Protects against Intrinsic Erosive Enamel Wear in situ. Caries Research, v. N/A, p. 6-pg., 2024-09-12. (19/24295-6, 18/12041-7, 21/00203-5, 19/26070-1, 17/04857-4, 18/18749-1)

VENTURA, TALITA MENDES OLIVEIRA; BUZALAF, MARILIA AFONSO RABELO; BAUMANN, TOMMY; PELA, VINICIUS TAIOQUI; NIEMEYER, SAMIRA HELENA; CRUSCA, EDSON; MARCHETTO, REINALDO; LUSSI, ADRIAN; CARVALHO, THIAGO SAADS. New insights into the protective effect of statherin-derived peptide for different acquired enamel pellicle formation times on the native human enamel surfaces. ARCHIVES OF ORAL BIOLOGY, v. 148, p. 7-pg., 2023-04-01. (19/16815-0, 19/26070-1)

ARAUJO, TAMARA T.; CARVALHO, THAMYRIS S.; DIONIZIO, ALINE; RODRIGUES, CHELSEA MARIA V. B. F.; HENRIQUE-SILVA, FLAVIO; CHIARATTI, MARCOS; SANTOS, ANGELICA; ALVES, LINDOMAR; FERRO, MILENE; BUZALAF, MARILIA A. R.. Acquired Pellicle and Biofilm Engineering by Rinsing with Hemoglobin Solution. Caries Research, v. 58, n. 3, p. 11-pg., 2024-03-01. (19/26070-1, 19/08032-5)

REIS, FERNANDA NAVAS; CAMARA, JOAO VICTOR FRAZAO; ABUNA, GABRIEL; MORAES, SAMANTA MASCARENHAS; DA SILVA, NATARA DIAS GOMES; VENTURA, TALITA MENDES OLIVEIRA; ARAUJO, TAMARA TEODORO; RODRIGUES, CHELSEA MARIA VILAS BOAS FEITOSA; PARDI, VANESSA; MURATA, RAMIRO MENDONCA; et al. Resveratrol alters oral biofilm in vitro and in vivo. Journal of Dentistry, v. 152, p. 9-pg., 2024-11-26. (19/26070-1, 22/07905-8, 20/13351-0)

ARAUJO, TAMARA TEODORO; DIONIZIO, ALINE; CARVALHO, THAMYRIS DE SOUZA; DEBORTOLLI, ANA LUIZA BOGAZ; VERTUAN, MARIELE; DE SOUZA, BEATRIZ MARTINES; CAMARA, JOAO VICTOR FRAZA; HENRIQUE-SILVA, FLAVIO; CHIARATTI, MARCOS; SANTOS, ANGELICA; et al. Acquired pellicle and biofilm engineering with CaneCPI-5: Insights from proteomic and microbiomics analysis. ARCHIVES OF ORAL BIOLOGY, v. 166, p. 8-pg., 2024-06-28. (19/26070-1, 19/08032-5)

REIS, FERNANDA NAVAS; CAMARA, JOAO VICTOR FRAZAO; DIONIZIO, ALINE; ARAUJO, TAMARA TEODORO; DA SILVA, NATARA DIAS GOMES; LEVY, FLAVIA MAUAD; XIMENES, VALDECIR FARIAS; BUZALAF, MARILIA AFONSO RABELO. Increase in plasma resveratrol levels and in acid-resistant proteins in the acquired enamel pellicle after use of resveratrol-containing orodispersible tablets. Journal of Dentistry, v. 143, p. 5-pg., 2024-03-10. (19/26070-1, 19/20935-0)

DE SOUZA, EDUARDO PEREIRA; FERRO, MILENE; PELA, VINICIUS TAIOQUI; FERNANDA-CARLOS, THAIS; BORGES, CECILIA GUIMARAES GIANNICO; TAIRA, EVEN AKEMI; VENTURA, TALITA MENDES OLIVEIRA; ARENCIBIA, ARIEL DOMINGO; BUZALAF, MARILIA AFONSO RABELO; HENRIQUE-SILVA, FLAVIO. Maquiberry Cystatins: Recombinant Expression, Characterization, and Use to Protect Tooth Dentin and Enamel. BIOMEDICINES, v. 11, n. 5, p. 18-pg., 2023-05-04. (19/26070-1, 22/13268-0, 21/11152-2)

FERRARI, CAROLINA RUIS; DE OLIVEIRA, TIAGO ESPINOSA; BUZALAF, MARILIA AFONSO RABELO; NETZ, PAULO AUGUSTO. Interaction of Statherin-Derived Peptide with the Surface of Hydroxyapatite: Perspectives Based on Molecular Dynamics Simulations. Caries Research, v. 58, n. 4, p. 13-pg., 2024-05-18. (19/26070-1)

REIS, FABIANA NAVAS; FRANCESE, MONIQUE MALTA; GOMES DA SILVA, NATARA DIAS; PELA, VINICIUS TAIOQUI; FRAZAO CAMARA, JOAO VICTOR; TREVIZOL, JULIANA SANCHES; PIERETTI, JOANA CLAUDIO; SEABRA, AMEDEA BAROZZI; PESSAN, JULIANO PELIM; HONORIO, HEITOR MARQUES; et al. Gels containing statherin-derived peptide protect against enamel and dentin erosive tooth wear in vitro. JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS, v. 137, p. 8-pg., 2023-01-01. (19/26070-1, 20/01634-7)

MIOTTO, DANYELLE SIQUEIRA; DUCHATSCH, FRANCINE; DIONIZIO, ALINE; BUZALAF, MARILIA AFONSO RABELO; AMARAL, SANDRA LIA. Physical Training vs. Perindopril Treatment on Arterial Stiffening of Spontaneously Hypertensive Rats: A Proteomic Analysis and Possible Mechanisms. BIOMEDICINES, v. 11, n. 5, p. 17-pg., 2023-05-06. (19/26117-8, 19/26070-1, 19/25603-6)

REIS, FABIANA NAVAS; FRANCESE, MONIQUE MALTA; DA SILVA, NATARA DIAS GOMES; PELA, VINICIUS TAIOQUI; CAMARA, JOAO VICTOR FRAZAO; TREVIZOL, JULIANA SANCHES; HONORIO, HEITOR MARQUES; CRUSCA, EDSON; MARCHETTO, REINALDO; BUZALAF, MARILIA AFONSO RABELO. Solutions containing a statherin-derived peptide reduce enamel erosion in vitro. Caries Research, v. N/A, p. 13-pg., 2023-01-11. (20/01634-7, 19/26070-1)

PELA, VINICIUS TAIOQUI; VENTURA, TALITA MENDES OLIVEIRA; TAIRA, EVEN AKEMI; THOMASSIAN, LARISSA TERCILIA GRIZZO; BRITO, LEONARDO; MATUHARA, YAN EIJI; HENRIQUE-SILVA, FLAVIO; GROISMAN, SONIA; CARVALHO, THIAGO SAADS; LUSSI, ADRIAN; et al. Use of Reflectometer Optipen to assess the preventive effect of a sugarcane cystatin on initial dental erosion in vivo. JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS, v. 141, p. 6-pg., 2023-03-17. (17/04857-4, 19/26070-1, 19/08437-5, 18/12041-7)

MORAES, SAMANTA MASCARENHAS; KOSHINO, LARISSA AYUMI; CARVALHO, THAMYRIS DE SOUZA; DE SOUZA, BEATRIZ MARTINES; HONORIO, HEITOR MARQUES; MAGALHAES, ANA CAROLINA; GARIB, DANIELA GAMBA; BUZALAF, MARILIA AFONSO RABELO. Effectiveness of Fluoride Varnishes for White Spot Lesion Prevention and Remineralization during Orthodontic Treatment: A Randomized Controlled Trial. Caries Research, v. 58, n. 6, p. 15-pg., 2024-12-01. (19/26070-1, 18/18147-1)