Introducción

1.- La caries dental es una enfermedad que depende del estilo de vida y de los hábitos adquiridos, con un componente bacteriano, que afecta a los tejidos duros dentales con un índice de casi  un 80% en los niños y el 90% en los adultos. Por ejemplo, en Estados Unidos y también in España, se gastan aproximadamente 100 millones de Euros anualmente en el servicio dental particular. In Inglaterra y Gales los gastos de la seguridad social para el tratamiento de esta enfermedad pueden llegar a costar más de 100 millones de esterlinas por año.  

En la desmineralización de la dentina aparte de la caries un papel muy importante juegan los sistemas adhesivos de resina. La adhesión entre la resina del adhesivo y la dentina se logra a través de la retención micromecánica por la penetración del adhesivo entre las fibras de colágeno expuestas en la dentina desmineralizada parcial o totalmente. Esta desmineralización que expone las fibras de colágeno se consigue mediante el acondicionamiento de la dentina con ácidos o monómeros  ácidos que se encuentran dentro de los sistemas de adhesión de auto-acondicionamiento. 

En odontología restauradora, más del 70% de los tratamientos consiste en  la sustitución y la reparación de las restauraciones existentes en boca porque la adhesión de los materiales restauradores a los tejidos duros se degrada con el paso del tiempo.  Esto se debe a la utilización de materiales sintéticos biocompatibles. Esto es debido a la utilización de materiales sintéticos, incompatibles que se aplican en un entorno biológico que no es el idóneo para su colocación siempre después de una eliminación ultraconservadora de la caries a la cual se le junta la no utilización de métodos biomiméticos que ayudan la adhesión, la  conservación o incluso a veces mejorar, el tejido reparado. Los materiales restauradores que liberan iones, cuando se aplican, solo pueden recuperar una parte de la funcionalidad biomecánica de la dentina cariada  debido a la pobre asociación mineral a nivel intrafibrilar. La recuperación total de la funcionalidad biomecánica de la dentina solo se puede conseguir después de la remineralización biomimética intrafibrilar con técnica de ingeniería tisular in situ. Si esta condición no se cumple el proceso de bio-mineralización debe considerarse incompleto. Además, las fibras de colágeno que se han remineralizado de forma inadecuada sufren una degradación por las bacterias o la activación  por parte del ácido de metaloproteinasas endogenas (MMPs) que se encuentran en la dentina.

Este será el primer proyecto en utilizar conceptos de ingeniería tisular in situ de bio-mineralización de grandes cavidades en los dientes y  superar los problemas que existen durante la restauración de grandes destrucciones cariosas mediante procedimientos de rehabilitación adhesiva mínimamente invasivos. Los clínicos serán capaces de aplicar sistemas adhesivos durante los tratamientos que serán capaces de biomineralizar la dentina, que alargaran la vida de las restauraciones de composite. Esto mejorará la calidad de las restauraciones dentales en clínica aumentando la rentabilidad del tratamiento.

Los objetivos de nuestra investigación serán de generar metodología innovadoras de ingeniería de tejidos in situ por biomateriales adhesivo inteligentes que restablece las propiedades biomecánicas de los tejidos dentarios desmineralizados in conjunción con procederás de rehabilitación dentales mínimamente invasiva. 

Esta técnica será capaz de:

-    Liberar iones y componentes biomiméticos 

-     Formar precursores de nano-nucleación de apatita en vez de micro- aglomerados.

-   Bio-remineralización jerárquica  de colágeno extra e intrafibrilar.

-   Inducir diferenciación de células estaminales células a los odontoblastos/fibroblastos.

-   Presentar una actividad antibacteriana en biofilm órale cariogenico

-   Recuperación de la funcionalidad biomecánica de las interfases adhesivas desmineralizadas alargando la vida útil de las restauraciones dentales.

2.- Dental caries is a behavioural, lifestyle disease with a bacterial component, affecting the dental hard tissues of almost 80% of children and 90% of adults. For instance, In the United States alone, more than 100 million dollars is spent annually on dental service, while the treatment of dental caries in England and Wales costs the NHS more than 100 million per annum. Apart from caries, resin-dentine bonding is another major reason for dentine demineralisation. The formation of resin-dentin bonds is accomplished predominantly by micromechanical retention via resin penetration and entanglement of exposed collagen fibrils in the partially or completely demineralized dentin. This is achieved by etching dentin with acids or acidic resin monomers derived from self-etching primers/adhesives to expose the collagen fibrils. Unfortunately, more than 70% of all restorative dentistry comprises of replacement/repair of existing restorations, as bonding to dental hard tissues still suffers from long-term interfacial failure. This is due to the use of synthetic, bio-incompatible materials placed in a hostile biological environment subsequent to ultra-conservative caries excavation, without using therapeutic and biomimetic methods to bond and maintain, or even improve, the repaired tissue.

Commonly-used ion-releasing restorative materials may only recover a small part of the biomechanical functionality of the carious dentine due to poor mineral association at the intrafibrillar level. The total re-establishment of biomechanical dentine functionality is only possible subsequent to intrafibrillar biomimetic remineralisation: if this condition is not satisfied then the biomineralisation process must be considered incomplete. Furthermore, inadequately remineralised collagen fibrils undergo degradation by bacterial or acid-activated dentine endogenous matrix metalloproteinases (MMPs).

This will be the first project to use high-impact In Situ bio-engineered concepts for bio-mineralise and restoring large cavities in teeth, overcoming existing problems that cannot be adequately addressed during the restoration of large carious dentine cavities with minimally invasive procedures. Clinicians will be able to apply therapeutic bonding materials capable of biomineralising carious dentine providing a durable foundation for resin composite restorations. This will improve the quality of dental restorations in routine practice, promoting cost-effective care.

The main aims of this research group focus on the generation of revolutionary techniques based on In Situ dental tissue engineering concepts and using smart resin-based biomaterials able to reestablish the biomechanical properties of mineral-depleted dental hard tissues in conjunction with minimally invasive dentistry.

These innovative approaches will be able to induce:

- Apatite nano-nucleation precursors (ANP) rather than micro-cluster agglomeration

- Hierarchical collagen bioremineralisation at intra- and extra-fibrillar level

- Differentiation of pulpal cells into reparative odontoblasts/fibroblast-like cells

- Bacteriostatic and/or antibacterial activity on caries biofilms

- Recovery of the biomechanical functionality of mineral-depleted bonded interfaces providing a long-term foundation for minimally invasive dental restorations.

Investigador principal

Miembros externos

David H Pashley (Georgia Regents University. Augusta. USA),Franklin Tay (Georgia Regents University. Augusta. USA),Manuel Toledano Pérez (Univ. de Granada),Raquel Osorio (Universidad de Granada),Víctor Feitosa (Universidade Federal do Ceará. Brazil),Lidiany Rodrigues (Universidade Federal do Ceará. Brazil),David Gillam (Queen Mary. University of London),Timothy F. Watson (King's College London),Francesco Mannocci (King's College London), Arzu Tezvergil-Mutluay (Institute of Dentistry. University of Turku. Finland),Angelo Putignano (Polytechnic of Marche. School of Dentistry. Ancona. Italy),Delia Brauer (Otto-Schott-Institut Friedrich-Schiller-Universität Jena. Germany),Marcelo Giannini (Universidade UNICAMP de Piracicaba. Brasil),Mário A. Sinhoreti (Universidade UNICAMP de Piracicaba. Brasil),Alessandro Loguercio (Universidade Ponta Grossa. Brasil),Alessandra Reis (Universidade Ponta Grossa.Brasil),Jeffrey.W.Stansbury (Biomaterials Research Center. University of Colorado. USA)

Doctorandos

Victoria Vivó Agulló,Regina Gascón Pellicer

Líneas de investigación

1.Ingeniería de tejidos dentarios duros in situ por biomateriales adhesivo inteligentes que restablece las propiedades biomecánicas de los tejidos dentarios desmineralizados.  

2. In Situ dental tissues engineering and therapeutic minimally invasive adhesive rehabilitation   

-Enamel Protection against Acid Soft Drinks: in Vitro/in Vivo study 
I.P: Salvatore Sauro, Romano Mongiorgi, Carlo Prati.
Entidad financiadora: Procter & Gamble-Italia. Fecha inicio/fin:2005/2006


-Micropermeability of experimental hydrophobic resin adhesives applied with the ethanol wet-bonding
I.P.: Salvatore Sauro . Entidad financiadora: KING’S COLLEGE LONDON RESEARCH USA FUNDING – Medical College of Georgia, Georgia, USA
Fecha inicio/fin: 2007
 

-DE FAZIO STUDENT RESEARCH AWARD - Effects of an alternative dentine pre-treatment: a microtensile and confocal-immunohistochemical study. I.P.: Salvatore Sauro . Entidad financiadora: SIDOC (Italian Society of Conservative Dentistry). Fecha:  2009
 
-The development of biomimetic/bioactive bonding procedures:  dentin re-mineralization induced by the interaction of bioactive glass with adhesive techniques. I.P.: Salvatore Sauro and Timothy Watson
Entidad financiadora: RALPH PHILLIPS STUDENT RESEARCH AWARD, SPONSORED BY THE FOUNDER'S FUND OF THE ACADEMY OF OPERATIVE DENTISTRY (AOD).Fecha inicio/fin: 2010/2011
 
-Premio Gaceta Dental - Remineralización biomimética y biocompatibilidad de un sistema de curado por luz con microrrelleno bioactivo embebido con ácido 4-oxoheptanodioico
Investigador responsable: Salvatore Sauro, Arlinda Luzi.
Entidad financiadora: Gaceta dental Fecha: 2014
 

Publicaciones de 2015:

Padovani GC*, Feitosa VP, Sauro S, Tay FR, Durán G, Paula AJ, Durán N. Título: Advances in Dental Materials through Nanotechnology: Facts, Perspectives and Toxicological Aspects. Trends Biotechnology. (2015).

D'Alpino PH*, Svizero ND, Bim Júnior O, Valduga CJ, Graeff CF, Sauro S.: Effects of age condition on the distribution and integrity of inorganic fillers in dental resin composites. Clinical Oral Investigation (2015)

Osorio R, Sauro S, Watson TF, Toledano M*.: Polyaspartic acid enhances dentine remineralization bonded with a zinc-doped Portland-based resin cement. International Endodontics Journal. (2015)

Sauro S*, Osorio R, Watson TF, Toledano M.: Influence of phosphoproteins' biomimetic analogs on remineralization of mineral-depleted resin-dentin interfaces created with ion-releasing resin-based systems. Trends Biotechnology. (2015)

Darvizeh A, Luzi A, Abedi Amin A, Oliveira-Ogliari A, Ogliari AF, Feitosa V, García-Esparza M, Pascual A, Sauro S* Título: In-situ nano-silica deposition and air-abrasion with Bioglass 45S5 or aluminium oxide: Effects on methacrylate bonding to yttria-tetragonal zirconia polycrystal. International Journal of Adhesion and Adhesives. (2015)

D Stramazzotti, C Coiana, A Zizzi, L Spazzafumo, Sauro S, AB D’Angelo, C Rubini, SD Aspriello*. Título Impact of smoking on guided tissue regeneration using a biocomposite poly (lactic-co-glycolic) acid/sub-micron size hydroxyapatite with a rubber dam as an alternative barrier. International journal of immunopathology and pharmacology.(2015)

Oliveira-Ogliari A, Collares F, Feitosa V, Sauro S*, Ogliari F; Moraes R.. Methacrylate bonding to zirconia by in situ silica nanoparticle surface deposition. Dental Materials (2015)

Publicaciones  de 2014:

-Osorio R, Yamauti M, Sauro S, Watson TF, Toledano M. Zinc Incorporation Improves Biological Activity of Beta-tricalcium Silicate Resin-based Cement.Journal of Endodontics (2014)

 -Feitosa VP, Sauro S, Ogliari FA, Ogliari AO, Yoshihara K, Zanchi CH, Correr-Sobrinho L, Sinhoreti MA, Correr AB, Watson TF, Van Meerbeek B. Impact of hydrophilicity and length of spacer chains on the bonding of functional monomers. Dental Materials, (2014)

 
-Tezvergil-Mutluay A, Seseogullari-Dirihan R, Feitosa VP, Tay FR, Watson TF, Pashley DH, Sauro S., Zoledronate and Ion-releasing Resins Impair Dentin Collagen Degradation. Journal of Dental Research, Vol.93 Pág:999-1004(2014)
 
-Zavattini A, Feitosa VP, Mannocci F, Foschi F, Babbar A, Luzi A, Ottria L, Mangani F, Casula I, Sauro S. Bonding ability of experimental resin-based materials containing(ion-releasing)-microfillers applied on water-wet or ethanol-wet root canal dentine. Journal of Adhesion and Adhesive, Vol:54, Pág: 214-223 (2014)
 
-Wang Z, Shen Y, Haapasalo M, Wang J, Jiang T, Wang Y, Watson TF, Sauro S.  Polycarboxylated microfillers incorporated into light-curable resin-based dental adhesives evoke remineralization at the mineral-depleted dentin. Journal of Biomaterials Science Polymer Edition, Vol:25, Pág,679-697 (2014) 
     
 -Toledano M, Aguilera FS, Sauro S, Cabello I, Osorio E, Osorio, R., Load cycling enhances bioactivity at the resin-dentin interface.  Dental Materials,Vol:30 Pág:e169-e188   (2014)

-Feitosa VP, Pomacóndor-Hernández C, Ogliari FA, Leal F, Correr AB, Sauro S. Chemical interaction of 10-MDP (methacryloyloxi-decyl-dihydrogen-phosphate) in zinc-doped self-etch adhesives.
Journal of Dentistry,Vol:42 Pág:359-365  (2014)

-Feitosa VP, Ogliari FA, Van Meerbeek B, Watson TF, Yoshihara K, Ogliari AO, Sinhoreti MA, Correr AB, Cama G, Sauro S.,  Can the hydrophilicity of functional monomers affect chemical interaction?
Journal of Dental Research, Vol:93, Pág:201-206. (2014)
 
-Toledano M, Osorio E, Aguilera FS, Sauro S, Cabello I, Osorio R.,  In vitro mechanical stimulation promoted remineralization at the resin/dentin interface.Journal of the Mechanical Behavior of Biomedical Materials, Vol:30 Pág:61-74 (2014)
 
- Feitosa VP, Bazzocchi MG, Putignano A; Orsini G, Luzi Luzi A, Sinhoreti MAC, Watson TF, Salvatore, Sauro.  Dicalcium phosphate (CaHPO4•2H2O) precipitation through ortho- or meta-phosphoric acid-etching: effects on the durability and nanoleakage/ultra-morphology of resin-dentine interfaces.  Journal of Dentistry, Vol:41, Pág:1068-1080 (2014)

 -Toledano M, Osorio E, Aguilera FS, Sauro S, Cabello I, Osorio R.   A Zn-doped etch-and-rinse adhesive may improve the mechanical properties and the integrity at the bonded-dentin interface.,  Dental Materials,  Vol:29,  Pág: e142-152
(2014) 
 
-Profeta AC, Mannocci F, Foxton R, Watson TF, Feitosa VP, De Carlo B, Mongiorgi R, Valdré G, Sauro S.,   Experimental etch-and-rinse adhesives doped with bioactive calcium silicate-based micro-fillers to generate therapeutic resin-dentin interfaces, Dental Materials, Vol:29,Pág, 729-741(2014)

 -Mestres G, Aguilera FS, Manzanares N, Sauro S, Osorio R, Toledano M, Ginebra MP., Magnesium phosphate cements for endodontic applications with improved long-term sealing ability. International Endodontic Journal, Vol:47, Pág:127-139 (2014).

Publicaciones de 2013:

- Sauro S, Osorio R, Osorio E, Watson TF, Toledano M.: Novel light-curable materials containing experimental bioactive micro-fillers remineralise. Journal of Biomaterials Science Polymer Edition.  Vol:24. Pág. 940-956. 2013.

-Sauro Salvatore, Osorio R, Fulgencio R, Watson TF, Cama G, Thompson I, Toledano M.: Remineralisation properties of innovative light-curable resin-based dental materials containing bioactive micro-fillers.  Journal of Materials Chemistry B  Vol: 1 Pág. 2624 – 2638, 2013.

-Sauro Salvatore, Osorio R, Watson TF, Toledano M.: Assessment of the quality of resin-dentin bonded interfaces: An AFM nano-indentation, µTBS and confocal ultramorphology study. Dental Materials. Vol.28. Pág. 622- 631. 2013.

- Feitosa VP, Watson TF, Vitti RP, Bacchi A, Correr-Sobrinho L, Correr AB, Sinhoreti MA, Sauro S.: Prolonged curing time reduces the effects of simulated pulpal pressure on the bond strength of one-step self-etch adhesives. Operative Dentistry             Vol: 38  Pág:545-554.  2013.

-Profeta CA, Mannocci F, Foxton RM, Salvatore, Sauro: Bioactive effects of a calcium/sodium phosphosilicate on the resin-dentine interface: a microtensile bond strength, scanning electron microscopy, and confocal microscopy study.  European Journal of Oral Sciences. Vol: 120      Pág.353 – 362. 2012.

- Sauro Salvatore, Vijay S, Deb S.: Development and assessment of experimental dental polymers with enhanced polymerisation, crosslink density and resistance to fluid permeability based on ethoxylated-Bisphenol-A-dimethacrylates and 2-Hydroxyethyl methacrylate. European Polymer Journal  Vol. 48. Pág.:   1466- 1474. 2012

- Almahdy A, Koller G, Sauro S, Bartsch JW, Sherriff M, Watson TF, Banerjee A.: Effects of MMP Inhibitors Incorporated within Dental Adhesives. Journal of Dental Research.   Vol.91.Pág. 605-611.  2012.

- Feitosa VP, Piovezan Fugolin AP, Correr AB, Salvatore Sauro: Effects of different photo-polymerization protocols on resin-dentine mu TBS, mechanical properties and cross-link density of a nano-filled resin composite. Journal of Dentistry Vol 40             Pág:802-809.  2012.

-Feitosa VP, Sauro Salvatore, Watson TF, Correr AB, Osorio R, Toledano M, Correr-Sobrinho L, Sinhoreti MA : Evaluation of the micro-mechanical strength of resin bonded-dentin interfaces submitted to short-term degradation strategies. Journal of the Mechanical Behavior of Biomedical Materials. Vol. 40  Pág.112-120. 2012.

 -Osorio R, Yamauti M, Sauro Salvatore, Toledano M. : Experimental Resin Cements Containing Bioactive Fillers Reduce Matrix Metalloproteinase-mediated Dentin Collagen Degradation. Journal of Endodontics . Vol. 38   Pág. 1227- 1232. 2012.

 - Bortolotti V, Fantazzini P, Mongiorgi R, Sauro Salvatore, Silvano Zanna.

: Hydration kinetics of cements by Time-Domain Nuclear Magnetic Resonance: Application to Portland-cement-derived endodontic pastes. Cement and Concrete Research    Vol. 42   Págs. 577- 582.  2012

-Feitosa Victor P, Leme AA, Sauro S, Correr-Sobrinho L, Watson TF, Sinhoreti MA, Correr AB.: Hydrolytic degradation of the resin-dentine interface induced by the simulated pulpal pressure, direct and indirect water ageing. Journal of Dentistry. Vol. 40   Págs. 1134-1143. 2012

-Sauro Salvatore, Watson TF, Thompson I, Toledano M, Nucci C, Banerjee A.: Influence of air-abrasion executed with polyacrylic acid-Bioglass 45S5 on the bonding performance of a resin-modified glass ionomer cement. European Journal of Oral Sciences. Vol. 120.  Págs. 168-177 . 2012.

-Almahdy A, Downey FC, Sauro S, Cook RJ, Sherriff M, Richards D, Watson TF, Banerjee A, Festy F.: Microbiochemical analysis of carious dentine using Raman and fluorescence spectroscopy. Caries Research.   Vol. 46   Págs. 432 -440. 2012

-Wang Z, Jiang T, Sauro S, Wang Y, Xing W, Liang S, Sa Y, Zhang C, Shen Y, Haapasalo M.: Nerve-targeted desensitizing toothpastes occlude dentin tubules and induce mineral precipitation.  American Journal of Dentistry.  Vol. 25   Págs. 26-30. 2012

- Salvatore Sauro, Watson TF, Thompson I, Banerjee A.: One-bottle self-etching adhesives applied to dentine air-abraded using bioactive glasses containing polyacrylic acid: An in vitro microtensile bond strength and confocal microscopy study. Journal of Dentistry.  Vol. 40     Págs.: 896- 905. 2012

-Salvatore Sauro, Osorio R, Watson TF, Toledano M.: Therapeutic effects of novel resin bonding systems containing bioactive glasses on mineral-depleted areas within the bonded-dentine interface.  Journal of Materials Science, Materials in Medicine .Vol. 23 Págs. 1521- 1532.2012

-Salvatore Sauro, Di Renzo S, Castagnola R, Grande NM, Plotino G, Foschi F, Mannocci F.: Comparison between water and ethanol wet bonding of resin composite to root canal dentin..American Journal of Dentistry  Vol. 24     Págs. inicial: 25   final: 30.. 2011

-Wang Z, Jiang T, Sauro S, Wang Y, Thompson I, Watson TF, Sa Y, Xing W, Shen Y, Haapasalo M.: Dentine remineralization induced by two bioactive glasses developed for air abrasion purposes.  Journal of Dentistry Vol. 39     Págs.: 746- 756. 2011

-Salvatore Sauro,Thompson I, Watson TF.: Effects of Common Dental Materials Used in Preventive or Operative Dentistry on Dentin Permeability and Remineralization. Operative Dentistry Vol. 36. Págs. 222 - 230. 2011

-De Carlo Boris, Salvatore Sauro, Deb S, Pitzolu G, Foschi F, Mannocci M, Zanna S, Mongiorgi R

: Porosity, Micro-Hardness and Morphology of White and Gray Portland Cements in Relation to Their Potential in the Development of New Dental Filling Materials.Journal of Adhesion Science and Technology. Vol. 26 .Págs.19 -26. 2011.

-Toledano M, Aguilera FS, Mannocci F, Pashley DH, Tay FR, Watson TF, Osorio R.

: Resin-dentin bonds to EDTA-treated vs. acid-etched dentin using ethanol wet-bonding. Part II: Effects of mechanical cycling load on microtensile bond strengths.Dental Materials  Vol. 27     Págs. 563- 572. 2011

- Wang Z, Jiang T, Sauro S, Pashley DH, Toledano M, Osorio R, Liang S, Xing W, Sa Y, Wang Y. : The dentine remineralization activity of a desensitizing bioactive glass-containing toothpaste: an in vitro study. Australian Dental Journal. Vol. 56.Págs.: 372- 381. 2011

  -Salvatore Sauro, Watson TF, Thompson I.: Ultramorphology and dentine permeability changes induced by prophylactic procedures on exposed dentinal tubules in middle dentine. Medicina Oral Patologia Oral y Cirugia Bucal.  Vol. 16      Págs. C1022-C1030. 2011.

-Aspriello SD, Piemontese M, Levrini L, Salvatore Sauro.: Ultramorphology of the root surface subsequent to hand-ultrasonic simultaneous instrumentation during non-surgical periodontal treatments. An in vitro study. Journal of Applied Oral Science. Vol. 19  Págs.: 74-81. 2011.