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![Schematic representation of proteoglycan attached to the collagen surface (not to scale). (A) Monomeric model of decorin based on the available crystal structure of the dimeric protein core [145]. The association of decorin with the collagen surface is based on a recently proposed model [48]. The glycosaminoglycan side-chain, based on the structure of chondroitin 4-sulfate [146] is positioned in a hypothetical region of the decorin protein core with associated ions. All molecular structures are available from the National Center for Biotechnology Information structure database (http://www.ncbi.nlm.nih.gov). (B) A not to scale schematic sketch of the interfibrillar supramolecular assemblies that interconnect collagen fibrils: (1) collagen fibril; (2) decorin protein core; (3) chondroitin 4-sulfate glycosaminoglycan. The known periodicity of these interfibrillar aggregates in register with the gap zones of collagen fibrils, present in most connective tissues, remains uncertain for mineralized tissues. (C) A high magnification image of a sample of acid-soluble collagen and decorin treated with cupromeronic blue, which reacts with glycosaminoglycans and demonstrates their assembly as interfibrillar co-aggregates (arrows) [127].](profile/Luiz-Bertassoni/publication/221892579/figure/fig7/AS:213115632394246@1427822134773/Schematic-representation-of-proteoglycan-attached-to-the-collagen-surface-not-to-scale.png)
Schematic representation of proteoglycan attached to the collagen surface (not to scale). (A) Monomeric model of decorin based on the available crystal structure of the dimeric protein core [145]. The association of decorin with the collagen surface is based on a recently proposed model [48]. The glycosaminoglycan side-chain, based on the structure of chondroitin 4-sulfate [146] is positioned in a hypothetical region of the decorin protein core with associated ions. All molecular structures are available from the National Center for Biotechnology Information structure database (http://www.ncbi.nlm.nih.gov). (B) A not to scale schematic sketch of the interfibrillar supramolecular assemblies that interconnect collagen fibrils: (1) collagen fibril; (2) decorin protein core; (3) chondroitin 4-sulfate glycosaminoglycan. The known periodicity of these interfibrillar aggregates in register with the gap zones of collagen fibrils, present in most connective tissues, remains uncertain for mineralized tissues. (C) A high magnification image of a sample of acid-soluble collagen and decorin treated with cupromeronic blue, which reacts with glycosaminoglycans and demonstrates their assembly as interfibrillar co-aggregates (arrows) [127].
Source publication
The prevention and treatment of dental caries are major challenges occurring in dentistry. The foundations for modern management of this dental disease, estimated to affect 90% of adults in Western countries, rest upon the dependence of ultrafine interactions between synthetic polymeric biomaterials and nanostructured supramolecular assemblies that...
Contexts in source publication
Context 1
... improved understanding of the specific nanostructural inter- action of proteoglycans with polymeric dental materials requires a critical reappraisal of proteoglycans as a biological entity and of their interaction with the collagen fibril surface [13,131] (Fig. 7). Decorin and biglycan, two members of the small leucine-rich re- peat (SLRP) family, are the proteoglycans predominantly expressed in dentin [28]. It has been shown that proteoglycans retain a pro- tein core that adopts a folded helical configuration stabilized by hydrogen bonds and hydrophobic and electrostatic interactions [132], ...Context 2
... expressed in dentin [28]. It has been shown that proteoglycans retain a pro- tein core that adopts a folded helical configuration stabilized by hydrogen bonds and hydrophobic and electrostatic interactions [132], which has also been suggested to bind to four or more col- lagen microfibrils via an array of hydrogen bonds (particularly decorin) (Fig. 7) ...Context 3
... important aspect that must be considered in this regard is the ability of viscous monomers to hermetically surround the highly intricate non-collagenous organic network. Fig. 7 offers a not to scale depiction of the proteoglycan structure, illustrating the complexity of the super-coiled spring-like protein core and interaction of the tape-like co-aggregates of antiparallel glycosami- noglycan strings bridging adjacent collagen fibrils. The participa- tion of water molecules and other ionic media is crucial to ...Citations
... Surrounding these tubules is a hypermineralized layer known as peritubular dentin, contrasted by a less mineralized, predominantly organic intertubular matrix. This matrix primarily contains type I collagen fibrils, NCPs, and proteoglycans, all reinforced by three-dimensional apatite mineral crystallites [35]. During dentin development, differentiated dentinoblasts meticulously secrete the dentin matrix [29]. ...
Objective: This review elucidates the mechanisms underpinning intrafibrillar mineralization, examines various amorphous calcium phosphate (ACP) stabilizers employed in dentin's intrafibrillar mineralization, and addresses the challenges encountered in clinical applications of ACP-based bioactive materials. Methods: The literature search for this review was conducted using three electronic databases: PubMed, Web of Science, and Google Scholar, with specific keywords. Articles were selected based on inclusion and exclusion criteria, allowing for a detailed examination and summary of current research on dentin remineralization facilitated by ACP under the influence of various types of stabilizers. Results: This review underscores the latest advancements in the role of ACP in promoting dentin remineralization, particularly intrafibrillar mineralization, under the regulation of various stabilizers. These stabilizers predominantly comprise non-collagenous proteins, their analogs, and polymers. Despite the diversity of stabilizers, the mechanisms they employ to enhance intrafibrillar remineralization are found to be interrelated, indicating multiple driving forces behind this process. However, challenges remain in effectively designing clinically viable products using stabilized ACP and maximizing intrafibrillar mineralization with limited materials in practical applications. Significance: The role of ACP in remineralization has gained significant attention in dental research, with substantial progress made in the study of dentin biomimetic mineralization. Given ACP's instability without additives , the presence of ACP stabilizers is crucial for achieving in vitro intrafibrillar mineralization. However, there is a lack of comprehensive and exhaustive reviews on ACP bioactive materials under the regulation of stabilizers. A detailed summary of these stabilizers is also instrumental in better understanding the complex process of intrafibrillar mineralization. Compared to traditional remineralization methods, bioactive materials capable of regulating ACP stability and controlling release demonstrate immense potential in enhancing clinical treatment standards.
... This means that TF3 can spontaneously bind to the active sites of collagen through hydrogen bonds, thereby achieving cross-linking of demineralized dentin collagen. However, it should be noted that the simulation may not fully reflect the real interaction (Bertassoni et al., 2012). Frontiers in Bioengineering and Biotechnology frontiersin.org ...
Objectives
To study the ability of theaflavin-3,3’-digallate (TF3)/ethanol solution to crosslink demineralized dentin collagen, resist collagenase digestion, and explore the potential mechanism.
Methods
Fully demineralized dentin blocks were prepared using human third molars that were caries-free. Then, these blocks were randomly allocated into 14 separate groups (n = 6), namely, control, ethanol, 5% glutaraldehyde (GA), 12.5, 25, 50, and 100 mg/ml TF3/ethanol solution groups. Each group was further divided into two subgroups based on crosslinking time: 30 and 60 s. The efficacy and mechanism of TF3’s interaction with dentin type I collagen were predicted through molecular docking. The cross-linking, anti-enzymatic degradation, and biomechanical properties were studied by weight loss, hydroxyproline release, scanning/transmission electron microscopy (SEM/TEM), in situ zymography, surface hardness, thermogravimetric analysis, and swelling ratio. Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy were utilized to explore its mechanisms. Statistical analysis was performed using one and two-way analysis of variance and Tukey’s test.
Results
TF3/ethanol solution could effectively crosslink demineralized dentin collagen and improve its resistance to collagenase digestion and biomechanical properties (p < 0.05), showing concentration and time dependence. The effect of 25 and 50 mg/ml TF3/ethanol solution was similar to that of 5% GA, whereas the 100 mg/mL TF3/ethanol solution exhibited better performance (p < 0.05). TF3 and dentin type I collagen are mainly cross-linked by hydrogen bonds, and there may be covalent and hydrophobic interactions.
Conclusion
TF3 has the capability to efficiently cross-link demineralized dentin collagen, enhancing its resistance to collagenase enzymatic hydrolysis and biomechanical properties within clinically acceptable timeframes (30 s/60 s). Additionally, it exhibits promise in enhancing the longevity of dentin adhesion.
... This procedure completely demineralizes the super cial dentin, exposes collagen brils, and activates the endogenous enzymes, such as matrix metalloproteinases (MMPs) and cysteine, in the dentin matrix [6,7]. The monomer resin of the adhesive cannot completely in ltrate and encapsulate the demineralized collagen brils due to the considerable complexity of the supramolecular structures of the dentin matrix on the nanometric scale and the hydrophobic nature of the adhesive monomers [8][9][10]. The hybrid layer at the adhesive-dentin interface consists of naked collagen brils, acid-activated dentin enzymes, and nano-channels full of loosely bonded water. ...
Objectives
To investigate the effect of neutral 10-methacryloyloxydecyl dihydrogen phosphate (MDP)-Na salt on the dentin bond strength and remineralization potential of etch-&-rinse adhesive.
Methods
Two experimental etch-&-rinse adhesives were prepared by integrating varying weight percentages (0wt%, 20wt%) of neutral MDP-Na into a base primer. A commercial etch-&-rinse adhesive Adper Single Bond 2 (SB, 3M ESPE) was used as control. Following this, microtensile bond strength (MTBS) was evaluated after subjecting the samples to 24 h of water storage or a 6-month incubation in artificial saliva. Fourier-transformed infrared spectrometry was used for assessment of the degree of conversion of the experimental adhesives and the adsorption properties of MDP-Na on the dentin organic matrix. Furthermore, the efficacy of neutral MDP-Na in facilitating the remineralization of two-dimensional collagen fibrils and the adhesive–dentin interface was investigated using transmission electron microscopy and selected-area electron diffraction.
Results
The addition of MDP-Na into the primer increased both the short- and long-term MTBS of the experimental adhesives (p = 0.000). No difference was noted in the degree of conversion between the control, 0 wt% and 20 wt% MDP-Na-containing groups (p = 0.336). The intra- and extra-fibrillar remineralization of the two-dimensional collagen fibril and dentin bond hybrid layer was confirmed by transmission electron microscopy and selected-area electron diffraction when the primer was added with MDP-Na.
Conclusions
The use of neutral MDP-Na results in high-quality hybrid layer that increase the dentin bond strength of etch-&-rinse adhesive and provides the adhesive with remineralizing capability. This approach may represent a suitable bonding strategy for improving the dentin bond strength and durability of etch-&-rinse adhesive.
... Bonding of composite resin to tooth involve series of different steps. The first step is to produce microporosities through acid etching/conditioning. 10 to 37% phosphoric acid is most commonly used acid conditioner/etchant. 6 This step is followed by appli-cation of low viscosity bonding agent that serves as a glue between composite resin and enamel/dentin. The intermediate layer of union formed between tooth and resin is known as hybrid layer. ...
... These fibrils become susceptible to degradation by endogenous collagenolytic enzymes (dentin matrix metalloproteinases -MMPs -and cysteine cathepsins) [7]. Furthermore, phosphoric acid was shown to cause changes in the molecular arrangement of collagen that favor the action of dentin MMPs [8], while also activating such enzymes [9]. ...
Objective: this study evaluated dentin microtensile bond strength (µTBS) and failure modes (at 24 h and one year), bonding interface regarding hybridization, surface morphology regarding demineralization, in situ met-alloproteinase (MMP) activity, and antibacterial effect of three dentin etchants compared to 35% phosphoric acid (PA). Materials and Methods: The Adper Single Bond 2 adhesive (3 M Oral Care) was applied on moist dentin etched with PA (control) or on air-dried dentin etched with 3% aluminum nitrate + 2% oxalic acid (AN), 6.8% ferric oxalate + 10% citric acid (FO), or 10% citric acid (CA). The µTBS test used 40 human teeth (n = 10). Failure modes and surface morphology were analyzed by scanning electron microscopy (n = 3), while bonding interface morphology and MMP activity were evaluated by laser scanning confocal microscopy (n = 3). Antibacterial activity was evaluated against S. Mutans biofilm by means of viable cells count (CFU/mL). Results: PA presented the highest bond strengths regardless of aging time. PA, AN, and CA showed stable bond strengths after one year of storage. Adhesive and mixed failures were predominant in all groups. Thin hybrid layers with short resin tags were observed for the experimental etchants. The AN-based etchant was able to inhibit MMP activity. All tested etchants presented antibacterial activity against S. Mutans biofilm. Significance: This study suggests different dentin etchants capable of inhibiting MMP activity while also acting as cavity disinfectants.
... DMP-1 is essential for phosphate metabolism and orchestrating mineral matrix deposition [49]. Meanwhile, type I collagen constitutes the most predominant component of the organic matrix in dentin [50]. Therefore, it can be tentatively concluded that M2-Exos are capable of accelerating odontoblast differentiation and the maturation of DPSCs in an early stage, which underlines the enormous potential of M2-Exos in inducing the formation of tubular dentin. ...
Introduction: Exosomes derived from M2 macrophages (M2-Exos) exhibit tremendous potential for inducing tissue repair and regeneration. Herein, this study was designed to elucidate the biological roles of M2-Exos in regenerative endodontic therapy (RET) compared with exosomes from M1 macrophages (M1-Exos). Methods: The internalization of M1-Exos and M2-Exos by dental pulp stem cells (DPSCs) and human umbilical vein endothelial cells (HUVECs) was detected by uptake assay. The effects of M1-Exos and M2-Exos on DPSC and HUVEC behaviors, including migration, proliferation, odonto/osteogenesis, neurogenesis, and angiogenesis were determined in vitro. Then, Matrigel plugs incorporating M2-Exos were transplanted subcutaneously into nude mice. Immunostaining for vascular endothelial growth factor (VEGF) and CD31 was performed to validate capillary-like networks. Results: M1-Exos and M2-Exos were effectively absorbed by DPSCs and HUVECs. Compared with M1-Exos, M2-Exos considerably facilitated the proliferation and migration of DPSCs and HUVECs. Furthermore, M2-Exos robustly promoted ALP activity, mineral nodule deposition, and the odonto/osteogenic marker expression of DPSCs, indicating the powerful odonto/osteogenic potential of M2-Exos. In sharp contrast with M1-Exos, which inhibited the neurogenic capacity of DPSCs, M2-Exos contributed to a significantly augmented expression of neurogenic genes and the stronger immunostaining of Nestin. Consistent with remarkably enhanced angiogenic markers and tubular structure formation in DPSCs and HUVECs in vitro, the employment of M2-Exos gave rise to more abundant vascular networks, dramatically higher VEGF expression, and widely spread CD31+ tubular lumens in vivo, supporting the enormous pro-angiogenic capability of M2-Exos. Conclusions: The multifaceted roles of M2-Exos in ameliorating DPSC and HUVEC functions potentially contribute to complete functional pulp–dentin complex regeneration.
... In the in-silico model, three types of interfaces were considered, i.e., those between the collagen fibrils and HA crystals in MCF, between the hydroxyapatite (HA) platelets in EFM, and between EFM and MCF (Table 1). Based on the information from the literature, the former one could be considered as a thin water layer between the collagen fibrils and mineral crystals in mineralized collagen fibrils (Bertassoni et al., 2012), with van der Waals bond controlling its opening-mode behavior and relatively weaker shear flow controlling its shear-mode behavior (Luo et al., 2011a;Ji, 2008b;Siegmund et al., 2008). The latter two could be considered as an organic interface consisting of NCPs (Morgan et al., 2015), with hydrogen bond dominating its opening-mode behavior, and a stronger show flow dominating its shear-mode behavior (Ji, 2008b;Siegmund et al., 2008). ...
This study proposed and validated a 2D finite element (FE) model for conducting in-silico simulations of in-situ nanoindentation tests on mineralized collagen fibrils (MCF) and the extrafibrillar matrix (EFM) within human cortical bone. Initially, a multiscale cohesive FE model was developed by adapting a previous model of bone lamellae, encompassing both MCF and EFM. Subsequently, nanoindentation tests were simulated in-silico using this model, and the resulting predictions were compared to AFM nanoindentation test data to verify the model's accuracy. The FE model accurately predicted nanoindentation results under wet conditions, closely aligning with outcomes obtained from AFM nanoindentation tests. Specifically, it successfully mirrored the traction/separation curve, nanoindentation modulus, plastic energy dissipation, and plastic energy ratio obtained from AFM nanoindentation tests. Additionally, this in-silico model demonstrated its ability to capture alterations in nanoindentation properties caused by the removal of bound water, by considering corresponding changes in mechanical properties of the collagen phase and the interfaces among bone constituents. Notably, significant changes in the elastic modulus and plastic energy dissipation were observed in both MCF and EFM compartments of bone, consistent with observations in AFM nanoindentation tests. These findings indicate that the proposed in-silico model effectively captures the influence of ultrastructural changes on bone's mechanical properties at sub-lamellar levels. Presently, no experimental methods exist to conduct parametric studies elucidating the ultrastructural origins of bone tissue fragility. The introduction of this in-silico model presents an invaluable tool to bridge this knowledge gap in the future.
... Adhesive dentistry relies on the removal of inorganic content of the dentin and enamel substrate, and the infiltration of these empty spaces with an adhesive resin. The depth of penetration of adhesive resin along with its capability to infiltrate laterally, is the primary cause of success/failure of all dentinal bonding procedures [10]. Matrix metalloproteinases (MMPs) are a part of collagen fibrils, and are responsible for the degradation of collagen fibrils. ...
A B S T R AC T Introduction: Advances in composite resins have changed the way restorative dentistry is now performed. The objective of restorative dentistry is to replace lost hard tissue with restorative material that has a good prognosis and longevity. In spite of the great improvements in the field of adhesive dentistry, hybridization of caries-affected dentin has been broadly avoided by clinicians and researchers. The loss of mineral content during a caries process is further compounded by action of matrix metalloproteinases (MMPs) on collagen of dentin. Recently, inhibition of MMPs has been the focus of research. Objectives: To compare the effect of MMP inhibitors on the bond strength of healthy dentin and caries-affected dentin. MMP inhibitors selected for this study were grape seed extract and riboflavin. Material and methods: Thirty-six extracted teeth were divided into two groups: healthy dentin and caries-affected dentin (CAD). Samples were grounded to expose dentinal surfaces. CAD samples were exposed to 10% citric acid for 5 minutes to simulate caries. The exposed dentinal surfaces of samples in each group were then treated, either with grape seed extract or riboflavin, followed by application of eighth-generation bonding agent and restoration with a composite resin, standardized to a specific height and diameter. This assembly was then subjected to testing in a universal testing machine to evaluate tensile bond strength (TBS) of adhesive layers. Results: The average TBS of healthy dentin treated with grape seed extract was found to be the highest (34.28 MPa) amongst the groups. The lowest TBS was found in the group with caries-affected dentin treated with riboflavin. There was a marked increase in TBS obtained in CAD after the application of MMP inhibitors. Conclusions: There is a significant difference between the bond strengths of healthy and caries-affected dentins. GSE and riboflavin both enhanced the bonding performance of eighth-generation bonding agent in both healthy dentin and CAD samples.
... Within these procedures, different types of polymers are extensively applied. The polymers have also set the stage for considerable advancements in the field of clinical dentistry [1]. A complex combination of biopolymers constitutes any biological tissue such as the tooth complex [1]. ...
... The polymers have also set the stage for considerable advancements in the field of clinical dentistry [1]. A complex combination of biopolymers constitutes any biological tissue such as the tooth complex [1]. These structures, which include enamel (the outer layer covering the tooth crown), dentin (the tissue immediately underneath the enamel), pulp (the sensory unit and vascular component of the tooth), cementum (the structure covering the root of the tooth), periodontal ligament (PDL-the soft tissue anchoring the root of the tooth), and alveolar bone (the site of anchorage for the tooth in the oral cavity) [2]-present a wide range of biopolymeric building blocks, in the sense that they are composed of proteins with repeating monomeric units having carbon as a structural backbone forming well-defined organic matrices [3]. ...
... In the genetic makeup, they help to regulate the functions of the odontobalsts and stem cells in the dental pulp [4]. Similarly, polypeptides, which are short polymers of amino acids, form the basic building blocks of the extracellular matrix (ECM) in the dentin, alveolar bone, cementum, PDL, and pulp in the form of collagen fibrils [1] and elastin (in the pulp and PDL/bone vasculature) [5]. In addition, polysaccharides that compose the ECM are another instance of biopolymers, which can be found in the tooth. ...
... Notably, the mechanical recovery was not limited to the dentin surface but was also observed in subsurface ED regions, indicating the diffusion of peptides into the completely demineralized dentinal matrix to facilitate remineralization. The ability of peptide-CS hydrogels to remineralize completely demineralized dentin heralds its potential application in extending the longevity of resin-dentin bonds by remineralizing the incompletely resin-infiltrated collagen matrix in the hybrid layer (Bertassoni et al. 2012). ...
Biomimetic strategies like peptide-guided collagen mineralization promise to enhance the effectiveness of dentin remineralization. We recently reported that rationally designed amelogenin-derived peptides P26 and P32 promoted apatite nucleation, mineralized collagen, and showed potential in enamel regrowth and dentin remineralization. To facilitate the clinical application of amelogenin-derived peptides and to uncover their effectiveness in repairing dentin, we have now implemented a chitosan (CS) hydrogel for peptide delivery and have investigated the effects of P26-CS and P32-CS hydrogels on dentin remineralization using 2 in situ experimental models that exhibited different levels of demineralization. The efficacy of the peptide-CS hydrogels in dentin repair was evaluated by characterizing the microstructure, mineral density, mineral phase, and nanomechanical properties of the remineralized samples. The new strategy of atomic force microscopy PeakForce quantitative nanomechanical mapping was used for direct visualization and nanomechanical analysis of repaired dentin lesions across the lesion depth. Results from the 2 models indicated the potential triple functions of peptide-CS hydrogels for dentin repair: building a highly organized protective mineralized layer on dentin, occluding dentinal tubules by peptide-guided in situ mineralization, and promoting biomimetic dentinal collagen remineralization. Importantly, peptides released from the CS hydrogel could diffuse into the dentinal matrix and penetrate the dentinal tubules, leading to both surface and subsurface remineralization and tubule occlusion. Given our previous findings on peptide-CS hydrogels’ potential for remineralizing enamel, we see further promise for hydrogels to treat tooth defects involving multiple hard tissues, as in the case of noncarious cervical lesions.
