Search Results (34)

Histatin peptides are a family of small histidine-rich cationic polypeptides produced by two genes, HTN1 and HTN3. They are found in salivary secretions from the parotid, sublingual, and submandibular salivary glands. These peptides undergo proteolytic cleavages to produce different histatin fragments which play multiple roles including wound healing, maintenance of enamel, and regulation of balance in the oral microbiome. In this review, we explored the expression, structural characteristics, and metal-ion-binding capacities of these peptides and how their functions are modulated by their structure. We also provide here an insight into the potential use of histatins as biomarkers and therapeutic peptides in the management of oral and non-oral diseases including cancer. Potential gaps in the current understanding of histatins that warrant further research have also been highlighted. Full article

Background and Objectives: Contemporary caries treatment seeks to preserve hard dental tissues as well as to promote lesion remineralization and biological tissue regeneration. While fluoride-based treatments remain the gold standard, their effectiveness has limitations, prompting interest in innovative remineralization technologies. Nano-hydroxyapatite (nano-HA) varnish and self-assembling peptide (SAP) P11-4 are promising biomimetic materials that promote enamel repair, yet long-term data on their efficacy are limited. The objectives of this study were to evaluate the effectiveness of nano-HA varnish and peptide P11-4 in restoring enamel surface hardness after artificial lesions in vitro and to compare them to a control group and fluoride varnish. Materials and Methods: Artificial enamel lesions were created on the buccal surfaces of 36 extracted human molars, which were randomly divided into four groups (n = 9): control, peptide P11-4, fluoride varnish, and nano-hydroxyapatite varnish. After applying the materials as per manufacturer instructions, specimens were stored in artificial saliva for 14 days. Enamel surface hardness was measured using the Vickers hardness test (HV) at baseline, after demineralization, and after remineralization. Statistical analysis was performed with “IBM SPSS 27.0” using non-parametric Kolmogorov–Smirnov, Kruskal–Wallis, Dunn’s, and Wilcoxon tests. Results: The mean baseline enamel hardness value was 323.95 (SD 33.47) HV. After 14 days of demineralization, the mean surface hardness of artificial enamel lesions significantly plummeted to 172.17 (SD 35.96) HV (p = 0.000). After 14 days of remineralization, the mean value significantly increased to 213.21 (SD 50.58) HV (p = 0.001). The results of the study revealed statistically significant enamel remineralization of the peptide P11-4 group in regard to the demineralized enamel (p < 0.05). In contrast, there were no significant results in other treatment groups (p > 0.05). Remineralization of enamel was the highest in samples from the P11-4 group (54.1%), followed by the nano-HA group (35.4%), FV group (17.8%), and control group (11.2%). There was a significant difference (p < 0.05) in the remineralizing ability between the peptide P11-4 and all other treatment groups. Conclusions: Self-assembling peptide P11-4 effectively remineralized artificial enamel lesions and proved to be significantly more effective compared to fluoride varnish and nano-hydroxyapatite varnish, showcasing its superior performance as a remineralizing agent. Full article

Peptide-based biomimetic treatments have gained increased attention in the dental field due to their biocompatibility and minimally invasive qualities. These biomimetic approaches can replicate the native architecture of dental tissues, thus contributing to higher success rates and improved longevity of restorations. The aim of this study was first to examine the biocompatibility and stability of an amelogenin peptide-based chitosan hydrogel (P26-CS) against salivary enzymes. Second, we aimed to evaluate its efficacy in biomimetically repairing human dental lesions in situ. White spot lesions (WSLs) in enamel and non-carious cervical lesions (NCCLs) in dentin were artificially created. Chitosan (CS) improved peptide stability, while remineralization of enamel sections with P26-CS was not impeded by salivary enzymes. The peptide was not cytotoxic, irritating, or sensitizing. Fluorescently labeled P26-CS penetrated ~300 μm into the enamel of WSLs and ~100 μm into the dentin of NCCLs. After peptide treatment, quantitative light-induced fluorescence (QLF) and microcomputed tomography (μCT) indicated a gain in mineral density of WSLs. In NCCLs, scanning electron microscopy showed that the dentin was covered by a mineral layer of needle-shaped crystals. Our results show that the repair of artificial WSLs and NCCLs was achieved by P26 peptide-guided remineralization and demonstrate its potential to repair dental lesions. Full article

This study investigates the microstructure of dental enamel following demineralization and re-mineralization processes, using DIAGNOdent scores and images obtained via scanning electron microscopy (SEM), atomic force microscopy (AFM), and microhardness (Vickers). The research evaluates the effects of two experimental hydrogels, Anti-Amelogenin isoform X (ABT260, S1) and Anti-Kallikrein L1 (K3014, S2), applied to demineralized enamel surfaces over periods of 14 and 21 days. The study involved 60 extracted teeth, free from cavities or other lesions, divided into four groups: a positive group (+), a negative group (−) and groups S1 and S2. The last three groups underwent demineralization with 37% phosphoric acid for 20 min. The negative group (−) was without remineralization treatment. The DIAGNOdent scores indicate that the S1 group treated with Anti-Amelogenin is more effective in remineralizing the enamel surface compared to the S2 group treated with Anti-Kallikrein. These findings were corroborated by SEM and AFM images, which revealed elongated hydroxyapatite (HAP) nanoparticles integrated into the demineralized structures. Demineralization reduced enamel microhardness to about 1/3 of a healthy one. Both tested hydrogels restored enamel hardness, with S1 being more effective than S2. Both peptides facilitated the interaction between the newly added minerals and residual protein binders on the enamel surface, thereby contributing to effective enamel restoration. Full article

The color masking ability of resin infiltration (RI) and curodont repair fluoride plus–self-assembling peptide (CRFP-SAP) was investigated under various simulated oral challenging conditions. Sixty-four extracted caries-free human canines were randomly divided into two groups: Group 1 (RI) and Group 2 (CRFP-SAP). The baseline color values of samples were recorded using a spectrophotometer (VITA Easyshade^® Advance 4.0 VITA Zahnfabrik, Bad Sackingen, Germany). The samples were stored in a demineralization solution for 4 days to induce artificial enamel lesions (AELs). The AELs of Groups I and II were treated with RI (Icon, DMG, Hamburg, Germany) and CRFP-SAP (vVARDIS, Zug, Switzerland), respectively, followed by color measurements. Each group was subjected to challenges such as remineralization, pH cycling, staining, and thermocycling, followed by color measurements. The difference between the mean ∆E (color difference value) of sound enamel and both treatment groups was less than 3.7 1-week post treatment. Meanwhile, the difference between the mean ∆E of RI-treated samples and all kinds of challenges was more than 3.7, while for the CRFP-SAP-treated samples, it was less than 3.7 for all kinds of challenges, except for the thermocycling, for which the mean ∆E difference was 4.3. RI and CRFP-SAP treatments were effective in masking the discoloration caused by AELs. However, the color was not stable for RI-treated samples, whereas it was stable for CRFP-SAP-treated samples under all challenges, except for thermocycling. Full article

AMELX mutations cause X-linked amelogenesis imperfecta (AI), known as AI types IE, IIB, and IIC in Witkop’s classification, characterized by hypoplastic (reduced thickness) and/or hypomaturation (reduced hardness) enamel defects. In this study, we conducted whole exome analyses to unravel the disease-causing mutations for six AI families. Splicing assays, immunoblotting, and quantitative RT-PCR were conducted to investigate the molecular and cellular effects of the mutations. Four AMELX pathogenic variants (NM_182680.1:c.2T>C; c.29T>C; c.77del; c.145-1G>A) and a whole gene deletion (NG_012494.2:g.307534_403773del) were identified. The affected individuals exhibited enamel malformations, ranging from thin, poorly mineralized enamel with a “snow-capped” appearance to severe hypoplastic defects with minimal enamel. The c.145-1G>A mutation caused a -1 frameshift (NP_001133.1:p.Val35Cysfs*5). Overexpression of c.2T>C and c.29T>C AMELX demonstrated that mutant amelogenin proteins failed to be secreted, causing elevated endoplasmic reticulum stress and potential cell apoptosis. This study reveals a genotype–phenotype relationship for AMELX-associated AI: While amorphic mutations, including large deletions and 5′ truncations, of AMELX cause hypoplastic-hypomaturation enamel with snow-capped teeth (AI types IIB and IIC) due to a complete loss of gene function, neomorphic variants, including signal peptide defects and 3′ truncations, lead to severe hypoplastic/aplastic enamel (AI type IE) probably caused by “toxic” cellular effects of the mutant proteins. Full article

The application of calcium coacervates (CCs) may hold promise for dental hard tissue remineralization. The aim of this study was to evaluate the effect of the infiltration of artificial enamel lesions with a CC and its single components including polyacrylic acid (PAA) compared to that of the self-assembling peptide P₁₁-4 in a pH-cycling (pHC) model. Enamel specimens were prepared from bovine incisors, partly varnished, and stored in demineralizing solution (DS; pH 4.95; 17 d) to create two enamel lesions per sample. The specimens were randomly allocated to six groups (n = 15). While one lesion per specimen served as the no-treatment control (NTC), another lesion (treatment, T) was etched (H₃PO₄, 5 s), air-dried and subsequently infiltrated for 10 min with either a CC (10 mg/mL PAA, 50 mM CaCl₂ (Ca) and 1 M K₂HPO₄ (PO₄)) (groups CC and CC + DS) or its components PAA, Ca or PO₄. As a commercial control, the self-assembling peptide P₁₁-4 (Curodont^TM Repair, Credentis, Switzerland) was tested. The specimens were cut perpendicularly to the lesions, with half serving as the baseline (BL) while the other half was exposed to either a demineralization solution for 20 d (pH 4.95; group CC + DS) or pHC for 28 d (pH 4.95, 3 h; pH 7, 21 h; all five of the other groups). The difference in integrated mineral loss between the lesions at BL and after the DS or pHC, respectively, was analyzed using transversal microradiography (ΔΔZ = ΔZ_pHC − ΔZ_baseline). Compared to the NTC, the mineral gain in the T group was significantly higher in the CC + DS, CC and PAA (p < 0.05, Wilcoxon). In all of the other groups, no significant differences between treated and untreated lesions were detected (p > 0.05). Infiltration with the CC and PAA resulted in a consistent mineral gain throughout the lesion body. The CC as well as its component PAA alone promoted the remineralization of artificial caries lesions in the tested pHC model. Infiltration with PAA further resulted in mineral gain in deeper areas of the lesion body. Full article

Dental caries is an avoidable and complex condition impacting billions of individuals worldwide, posing a specific concern among younger generations, despite the progress of oral hygiene products. This deterioration occurs due to the acid demineralization of tooth enamel, leading to the loss of minerals from the enamel subsurface. The remineralisation of early enamel carious lesions could prevent the cavitation of teeth. The enamel protein amelogenin constitutes 90% of the total enamel matrix protein and plays a key role in the bio mineralisation process. The aim of this study is to investigate the self-assembly microstructure and reticulation behaviour of a newly developed bioactive hydrogel with leucine-rich amelogenin peptide (LRAP) intended for enamel remineralisation. SEM, AFM, UV-VIS, and FTIR analyses emphasize the ability of peptides to promote cell adhesion and the treatment of early carious lesions. In conclusion, short-chain peptides can be used in hydrogels for individual or professional use. Full article

Biotechnology and artificial intelligence have sparked a revolution in dentistry, with a focus on restoring natural tissue functions. This transformation has given rise to bioactive materials, inspired by biomimetics, aimed at replicating the processes found in nature. As synthetic biology advances, there is a heightened focus on signaling systems crucial for bio-based diagnostics and therapeutics. Dentistry now harnesses synthetic proteins for tissue regeneration and dental material enhancement. A current research priority is bacterial biofilm inhibition, vital for dental health. Given the role of Streptococcus mutans in dental caries, the development of synthetic antimicrobial peptides targeting this bacterium is underway. The balance of dental enamel between demineralization and remineralization impacts caries formation. Factors such as the presence of hydroxyapatite and salivary peptides influence enamel health. Recent studies have spotlighted salivary protein-inspired peptides for enhanced remineralization. In the realm of bone regeneration, synthetic proteins like bone morphogenetic proteins (BMP) have been spotlighted, earning FDA approval. Research is currently delving into peptides such as cementum protein 1 peptide (CEMP-1-p1) and parathyroid hormone variants like PTH (1-34), underscoring their potential in advancing dental and bone health. Full article

The purpose of the study is to develop a novel peptide for caries management. Gallic-Acid-Polyphemusin-I (GAPI) was synthesised by grafting Polyphemusin I (PI) and gallic acid (GA). Biocompatibility was evaluated using a Cell Counting Kit-8 Assay. Antimicrobial properties were assessed using minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC). The bacterial and fungal morphology after GAPI treatment was investigated using transmission electron microscopy (TEM). The architecture of a consortium biofilm consisting of Streptococcus mutans, Lacticaseibacillus casei and Candida albicans was evaluated using scanning electron microscopy (SEM) and confocal laser scanning microscopy. The growth kinetics of the biofilm was examined using a propidium monoazide–quantitative polymerase chain reaction. The surface and calcium-to-phosphorus molar ratio of GAPI-treated enamel after pH cycling were examined with SEM and energy-dispersive X-ray spectroscopy. Enamel crystal characteristics were analysed using X-ray diffraction. Lesion depths representing the enamel’s mineral loss were assessed using micro-computed tomography. The MIC of GAPI against S. mutans, L. casei and C. albicans were 40 μM, 40 μM and 20 μM, respectively. GAPI destroyed the biofilm’s three-dimensional structure and inhibited the growth of the biofilm. SEM showed that enamel treated with GAPI had a relatively smooth surface compared to that treated with water. The calcium-to-phosphorus molar ratio of enamel treated with GAPI was higher than that of the control. The lesion depths and mineral loss of the GAPI-treated enamel were less than the control. The crystallinity of the GAPI-treated enamel was higher than the control. This study developed a biocompatible, mineralising and antimicrobial peptide GAPI, which may have potential as an anti-caries agent. Full article

Excess albumin in enamel is a characteristic of the prevalent developmental dental defect known as chalky teeth or molar hypomineralization (MH). This study uses proteomic analyses of pig teeth to discern between developmental origin and post-eruptive contamination and to assess the similarity to hypomineralized human enamel. Here, the objective is to address the urgent need for an animal model to uncover the etiology of MH and to improve treatment. Porcine enamel is chalky and soft at eruption; yet, it hardens quickly to form a hard surface and then resembles human teeth with demarcated enamel opacities. Proteomic analyses of enamel from erupted teeth, serum, and saliva from pigs aged 4 (n = 3) and 8 weeks (n = 2) and human (n = 4) molars with demarcated enamel opacities show alpha-fetoprotein (AFP). AFP expression is limited to pre- and perinatal development and its presence in enamel indicates pre- or perinatal inclusion. In contrast, albumin is expressed after birth, indicating postnatal inclusion into enamel. Peptides were extracted from enamel and analyzed by nano-liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) after tryptic digestion. The mean total protein number was 337 in the enamel of all teeth with 13 different unique tryptic peptides of porcine AFP in all enamel samples but none in saliva samples. Similarities in the composition, micro-hardness, and microstructure underscore the usefulness of the porcine model to uncover the MH etiology, cellular mechanisms of albumin inclusion, and treatment for demarcated opacities. Full article

The recent understanding of the etiology and pathology of dental caries has shifted its treatment from invasive drill and fill conventional strategies to noninvasive and/or minimally invasive approaches. Guided tissue regeneration (GTR) is a well-established therapeutic approach in medicine and periodontal and oral surgery. Recently, the concept of biomimetic regeneration has been further expanded to treat the loss of hard dental tissues. Self-assembling peptides have emerged as a promising biomaterial for biomimetic regeneration due to their ability to construct a protein scaffold in the body of early carious lesions and provide a matrix that promotes remineralization. This review article accompanies the development of self-assembling peptide P₁₁-4 for the treatment of initial carious lesions. In vitro and in vivo studies on the safety, clinical applicability, and efficacy of P₁₁-4 are discussed. Furthermore, different treatment options and potential areas of application are presented. Full article

The enamel matrix protein Ameloblastin (Ambn) has critical physiological functions, including regulation of mineral formation, cell differentiation, and cell–matrix adhesion. We investigated localized structural changes in Ambn during its interactions with its targets. We performed biophysical assays and used liposomes as a cell membrane model. The xAB2N and AB2 peptides were rationally designed to encompass regions of Ambn that contained self-assembly and helix-containing membrane-binding motifs. Electron paramagnetic resonance (EPR) on spin-labeled peptides showed localized structural gains in the presence of liposomes, amelogenin (Amel), and Ambn. Vesicle clearance and leakage assays indicated that peptide–membrane interactions were independent from peptide self-association. Tryptophan fluorescence and EPR showed competition between Ambn–Amel and Ambn–membrane interactions. We demonstrate localized structural changes in Ambn upon interaction with different targets via a multitargeting domain, spanning residues 57 to 90 of mouse Ambn. Structural changes of Ambn following its interaction with different targets have relevant implications for the multifunctionality of Ambn in enamel formation. Full article

Currently, it remains unclear which specific peptides could be appropriate for applications in different fields of dentistry. The aim of this scoping review was to scan the contemporary scientific papers related to the types, uses and applications of peptides in dentistry at the moment. Literature database searches were performed in the following databases: PubMed/MEDLINE, Scopus, Web of Science, Embase, and Scielo. A total of 133 articles involving the use of peptides in dentistry-related applications were included. The studies involved experimental designs in animals, microorganisms, or cells; clinical trials were also identified within this review. Most of the applications of peptides included caries management, implant osseointegration, guided tissue regeneration, vital pulp therapy, antimicrobial activity, enamel remineralization, periodontal therapy, the surface modification of tooth implants, and the modification of other restorative materials such as dental adhesives and denture base resins. The in vitro and in vivo studies included in this review suggested that peptides may have beneficial effects for treating early carious lesions, promoting cell adhesion, enhancing the adhesion strength of dental implants, and in tissue engineering as healthy promotors of the periodontium and antimicrobial agents. The lack of clinical trials should be highlighted, leaving a wide space available for the investigation of peptides in dentistry. Full article

A relevant alternative to enamel matrix derivatives from animal origin could be the use of synthetic amelogenin-derived peptides. This study aimed to assess the effect of a synthetic amelogenin-derived peptide (ADP-5), alone or included in an experimental gellan–xanthan hydrogel, on periodontal cell behavior (gingival fibroblasts, periodontal ligament cells, osteoblasts and cementoblasts). The effect of ADP-5 (50, 100, and 200 µg/mL) on cell metabolic activity was examined using Alamar blue assay, and cell morphology was assessed by confocal imaging. An experimental gellan–xanthan hydrogel was then designed as carrier for ADP-5 and compared to the commercial gel Emdogain^®. Alizarin Red was used to determine the periodontal ligament and cementoblasts cell mineralization. The inflammatory profile of these two cells was also quantified using ELISA (vascular endothelial growth factor A, tumor necrosis factor α, and interleukin 11) mediators. ADP-5 enhanced cell proliferation and remineralization; the 100 µg/mL concentration was more efficient than 50 and 200 µg/mL. The ADP-5 experimental hydrogel exhibited equivalent good biological behavior compared to Emdogain^® in terms of cell colonization, mineralization, and inflammatory profile. These findings revealed relevant insights regarding the ADP-5 biological behavior. From a clinical perspective, these outcomes could instigate the development of novel functionalized scaffold for periodontal regeneration. Full article