Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: closed (20 December 2023) | Viewed by 55122

Special Issue Editors


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Guest Editor
1. Solid State Physics and Nanostructures Department, Voronezh State University, University Sq. 1, 394018 Voronezh, Russia
2. Scientific and Educational Center “Nanomaterials and Nanotechnologies”, Ural Federal University Named after the First President of Russia B. N. Yeltsin, Mir av., 620002 Yekaterinburg, Russia
Interests: dental tissue and biofilm; caries; new bioactive materials; biomimetic approach; regeneration of dental tissue; personalized express diagnostics; interaction of synchrotron radiation with matter; modeling of physical processes; enhanced raman scattering

E-Mail Website
Guest Editor
Solid State Physics and Nanostructures Department, Voronezh State University, University Sq. 1, 394018 Voronezh, Russia
Interests: bioactive materials for dentistry; biomineralization; structure of biogenic substance; spectroscopic research methods for medicine

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute your valuable work to this Special Issue on “Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research”.

Novel biomaterials and pharmaceutical agents for the effective mineralization of dental tissue are in the focus of modern interdisciplinary research and biomedical science. The basis of modern therapeutic and preventive dentistry is the desire to preserve the natural structure of natural hard tissue as much as possible, or to reproduce it. As a result, the main modern non-invasive enamel restoration strategy is focused on the protection and preservation of dental tissue because of its biomineralization, the repair of damage, and the elimination of defects.

This Special Issue focuses on the problems and challenges associated with the creation, use and modification of new biomaterials and agents for pharmaceutical and biomedical applications in dental research, as well as the study of the effects of drugs on mineralized tissues of the human body and related processes.

Research articles, review articles and short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website. We look forward to receiving your contributions.

Dr. Pavel Seredin
Dr. Dmitry Goloshchapov
Guest Editors

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Keywords

  • biomaterials 
  • pharmaceutical agents 
  • dentifrice and drugs 
  • dental tissue 
  • biomineralization

Published Papers (33 papers)

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Research

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17 pages, 7019 KiB  
Article
Modulation of TRPV1 on Odontoblast-like Cells Using Capsazepine-Loaded Nanogels
by Lilia Jadith Bernal-Cepeda, Ronald Andrés Jiménez, Myriam L. Velandia-Romero, Paola Acosta-Guzmán and Jaime E. Castellanos
Pharmaceutics 2024, 16(3), 355; https://doi.org/10.3390/pharmaceutics16030355 - 03 Mar 2024
Viewed by 904
Abstract
The modulation of TRPV1 emerges as a promising strategy for dental pain management. This study aimed to assess TRPV1 modulation in a human odontoblast-like cell model using Capsazepine (CZP) loaded in a nanogel delivery system. Gelatin nanogels, synthesized via the emulsification-gelation technique, were [...] Read more.
The modulation of TRPV1 emerges as a promising strategy for dental pain management. This study aimed to assess TRPV1 modulation in a human odontoblast-like cell model using Capsazepine (CZP) loaded in a nanogel delivery system. Gelatin nanogels, synthesized via the emulsification-gelation technique, were characterized and loaded with the TRPV1 antagonist, CZP. HPLC determined a remarkable 67.5 ± 0.04% CZP loading efficiency, with 71.7% of nanogels falling within the 300–950 nm size range, as evidenced by light microscopy. Moreover, CZP-loaded nanogels had a low cytotoxicity. An FTIR analysis showed no adverse chemical interactions, ensuring stability and active release. When examining biological responses, TRPV1 expression and channel activity were assessed in odontoblast-like cells. On the fifth day post-treatment, cells treated with CZP-loaded nanogels exhibited an increased TRPV1 expression and a reduction in calcium fluxes after agonist stimulus (F/F0 ratio 1.18 ± 0.18), resembling the response in free CZP-treated cells (1.28 ± 0.15). A two-way analysis of variance and the Tukey’s test were used to determine statistical significance (p < 0.05). This delivery system, proven to be economical and straightforward, holds promise for dental pain management and potential local use. Local administration minimizes systemic adverse effects, making it a practical solution for releasing molecules in the oral cavity. Full article
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24 pages, 3405 KiB  
Article
In Vitro Characterization of Reversine-Treated Gingival Fibroblasts and Their Safety Evaluation after In Vivo Transplantation
by Carlos Miguel Marto, Mafalda Laranjo, Ana Cristina Gonçalves, Anabela Paula, Joana Jorge, Rui Caetano-Oliveira, Maria Inês Sousa, Bárbara Oliveiros, João Ramalho-Santos, Ana Bela Sarmento-Ribeiro, Manuel Marques-Ferreira, António Cabrita, Maria Filomena Botelho and Eunice Carrilho
Pharmaceutics 2024, 16(2), 207; https://doi.org/10.3390/pharmaceutics16020207 - 31 Jan 2024
Viewed by 1201
Abstract
Reversine is a purine derivative that has been investigated with regard to its biological effects, such as its anticancer properties and, mostly, its ability to induce the dedifferentiation of adult cells, increasing their plasticity. The obtained dedifferentiated cells have a high potential for [...] Read more.
Reversine is a purine derivative that has been investigated with regard to its biological effects, such as its anticancer properties and, mostly, its ability to induce the dedifferentiation of adult cells, increasing their plasticity. The obtained dedifferentiated cells have a high potential for use in regenerative procedures, such as regenerative dentistry (RD). Instead of replacing the lost or damaged oral tissues with synthetic materials, RD uses stem cells combined with matrices and an appropriate microenvironment to achieve tissue regeneration. However, the currently available stem cell sources present limitations, thus restricting the potential of RD. Based on this problem, new sources of stem cells are fundamental. This work aims to characterize mouse gingival fibroblasts (GFs) after dedifferentiation with reversine. Different administration protocols were tested, and the cells obtained were evaluated regarding their cell metabolism, protein and DNA contents, cell cycle changes, morphology, cell death, genotoxicity, and acquisition of stem cell characteristics. Additionally, their teratoma potential was evaluated after in vivo transplantation. Reversine caused toxicity at higher concentrations, with decreased cell metabolic activity and protein content. The cells obtained displayed polyploidy, a cycle arrest in the G2/M phase, and showed an enlarged size. Additionally, apoptosis and genotoxicity were found at higher reversine concentrations. A subpopulation of the GFs possessed stem properties, as supported by the increased expression of CD90, CD105, and TERT, the existence of a CD106+ population, and their trilineage differentiation capacity. The dedifferentiated cells did not induce teratoma formation. The extensive characterization performed shows that significant functional, morphological, and genetic changes occur during the dedifferentiation process. The dedifferentiated cells have some stem-like characteristics, which are of interest for RD. Full article
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19 pages, 5118 KiB  
Article
Trans-Cinnamaldehyde—Fighting Streptococcus mutans Using Nature
by Zilefac Brian Ngokwe, Amit Wolfoviz-Zilberman, Esi Sharon, Asher Zabrovsky, Nurit Beyth, Yael Houri-Haddad and Dana Kesler-Shvero
Pharmaceutics 2024, 16(1), 113; https://doi.org/10.3390/pharmaceutics16010113 - 15 Jan 2024
Viewed by 681
Abstract
Streptococcus mutans (S. mutans) is the main cariogenic bacterium with acidophilic properties, in part due to its acid-producing and -resistant properties. As a result of this activity, hard tooth structures may demineralize and form caries. Trans-cinnamaldehyde (TC) is a phytochemical from [...] Read more.
Streptococcus mutans (S. mutans) is the main cariogenic bacterium with acidophilic properties, in part due to its acid-producing and -resistant properties. As a result of this activity, hard tooth structures may demineralize and form caries. Trans-cinnamaldehyde (TC) is a phytochemical from the cinnamon plant that has established antibacterial properties for Gram-positive and -negative bacteria. This research sought to assess the antibacterial and antibiofilm effects of trans-cinnamaldehyde on S. mutans. TC was diluted to a concentration range of 156.25–5000 μg/mL in dimethyl sulfoxide (DMSO) 0.03–1%, an organic solvent. Antibacterial activity was monitored by testing the range of TC concentrations on 24 h planktonic growth compared with untreated S. mutans. The subminimal bactericidal concentrations (MBCs) were used to evaluate the bacterial distribution and morphology in the biofilms. Our in vitro data established a TC MBC of 2500 μg/mL against planktonic S. mutans using a microplate spectrophotometer. Furthermore, the DMSO-only controls showed no antibacterial effect against planktonic S. mutans. Next, the sub-MBC doses exhibited antibiofilm action at TC doses of ≥625 μg/mL on hydroxyapatite discs, as demonstrated through biofilm analysis using spinning-disk confocal microscopy (SDCM) and high-resolution scanning electron microscopy (HR-SEM). Our findings show that TC possesses potent antibacterial and antibiofilm properties against S. mutans. Our data insinuate that the most effective sub-MBC of TC to bestow these activities is 625 μg/mL. Full article
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13 pages, 2156 KiB  
Article
Tunable Release of Calcium from Chitosan-Coated Bioglass
by Vuk Uskoković, Gabriel Abuna, Joseph Ryan Hampton and Saulo Geraldeli
Pharmaceutics 2024, 16(1), 39; https://doi.org/10.3390/pharmaceutics16010039 - 27 Dec 2023
Cited by 1 | Viewed by 750
Abstract
Bioglass presents a standard biomaterial for regeneration of hard tissues in orthopedics and dentistry. The notable osteo-inductive properties of bioglass are largely due to the release of calcium ions from it. However, this release is not easily controllable and can often be excessive, [...] Read more.
Bioglass presents a standard biomaterial for regeneration of hard tissues in orthopedics and dentistry. The notable osteo-inductive properties of bioglass are largely due to the release of calcium ions from it. However, this release is not easily controllable and can often be excessive, especially during the initial interaction of the biomaterial with the surrounding tissues. Consequently, this excessive release can deplete the calcium content of the bioglass, ultimately reducing its overall bioactivity. In this study, we have tested if applying biopolymer chitosan coatings of different thicknesses would be able to mitigate and regulate the calcium ion release from monodisperse bioglass nanoparticles. Calcium release was assessed for four different chitosan coating thicknesses at different time points over the period of 28 days using a fluorescence quencher. Expectedly, chitosan-coated particles released less calcium as the concentration of chitosan in the coating solution increased, presumably due to the increased thickness of the chitosan coating around the bioglass particles. The mechanism of release remained constant for each coating thickness, corresponding to anomalous, non-Fickian diffusion, but the degree of anomalousness increased with the deposition of chitosan. Zeta potential testing showed an expected increase in the positive double layer charge following the deposition of the chitosan coating due to the surface exposure of the amine groups of chitosan. Less intuitively, the zeta potential became less positive as thickness of the chitosan coating increased, attesting to the lower density of the surface charges within thicker coatings than within the thinner ones. Overall, the findings of this study demonstrate that chitosan coating efficiently prevents the early release of calcium from bioglass. This coating procedure also allows for the tuning of the calcium release kinetics by controlling the chitosan concentration in the parent solution. Full article
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22 pages, 7541 KiB  
Article
Sustainable Treatment of Oral Traumatic Ulcers with Licorice Containing Hydrogels: Integrating Computational Modeling, Quality by Design, Green Synthesis, and Molecular Biological Evaluation
by Sarah G. Moussa, Nada M. El Hoffy, Yara Y. Mouselhy, Ramy Mubarak, Reem T. Attia, Noha Khalil and Sherif A. Amer
Pharmaceutics 2023, 15(12), 2734; https://doi.org/10.3390/pharmaceutics15122734 - 06 Dec 2023
Viewed by 1031
Abstract
The urge to implement innovative approaches that align with eco-friendly practices and hold promise for enhancing oral health while promoting environmental sustainability has been increasing. This current work aims to develop a sustainable treatment for oral traumatic ulcers using licorice-based hydrogels (LHGs) containing [...] Read more.
The urge to implement innovative approaches that align with eco-friendly practices and hold promise for enhancing oral health while promoting environmental sustainability has been increasing. This current work aims to develop a sustainable treatment for oral traumatic ulcers using licorice-based hydrogels (LHGs) containing hydroxyethyl cellulose (HEC) as the green gelling agent. Licorice root aqueous extract was phytochemically profiled using UPLC-ESI-MS/MS. Forty-three compounds were detected, with Glycyrrhizic acid being the major component of the extract (34.85 ± 2.77%). By implementing a Quality by Design (QbD) approach, the study investigates the effects of different licorice extract and HEC concentrations on key variables such as pH and viscosity of the prepared formulations, ulcer and wound healing scores, and tissue growth factors via a Full Factorial Experimental Design. The LHGs exhibited desirable consistency, spreadability, and clarity. Statistical analysis, employing an ANOVA test, revealed the high significance of the constructed models with the licorice concentration being the key independent factor affecting all dependent outputs. The pH as well as the viscosity of the prepared LHGs were positively influenced by licorice extract concentration, with higher concentrations leading to increased alkalinity and viscosity. Rheological behavior analysis revealed a pseudoplastic flow with demonstrated thixotropy which is advantageous for application and prolongation of residence time. The wound healing process was assessed through ulcer size, traumatic ulcer healing score (UHS), collagen-1 expression (COL-1), growth factors (EGF, VEGF), pro-inflammatory markers (TNF-α), wound healing score (WHS). LHGs prepared using higher levels of both factors, 30% dried licorice root extract and 4% HEC, demonstrated enhanced wound healing, elevated growth factor expression of 66.67% and 23.24%, respectively, and 88% reduced inflammation compared to the control group, indicating their potential in expediting oral ulcer recovery. Overall, these findings highlight the promising role of green licorice-based hydrogels in promoting sustainable oral mucosal healing. Full article
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11 pages, 12728 KiB  
Article
Development of a Novel Peptide with Antimicrobial and Mineralising Properties for Caries Management
by Olivia Lili Zhang, John Yun Niu, Ollie Yiru Yu, May Lei Mei, Nicholas Stephen Jakubovics and Chun Hung Chu
Pharmaceutics 2023, 15(11), 2560; https://doi.org/10.3390/pharmaceutics15112560 - 31 Oct 2023
Cited by 1 | Viewed by 938
Abstract
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 [...] Read more.
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
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13 pages, 958 KiB  
Article
The Effect of Salbutamol and Budesonide Pediatric Doses on Dental Enamel and Packable and Flowable Composites: Microhardness, Surface Roughness and Color
by Maria Salem Ibrahim, Fatimah Mohammed Alatiyyah, Khawla Abbas Mohammed, Hibah Nouh Alhawaj, Abdulrahman A. Balhaddad and Ahmed Salem Ibrahim
Pharmaceutics 2023, 15(11), 2527; https://doi.org/10.3390/pharmaceutics15112527 - 25 Oct 2023
Cited by 1 | Viewed by 1089
Abstract
Objective: To assess and compare the effects of two pediatric anti-asthmatic medication doses on the microhardness of enamel and microhardness, surface roughness and color of restorative materials. Methods: Human enamel samples and packable and flowable composite restorations were used. The samples were exposed [...] Read more.
Objective: To assess and compare the effects of two pediatric anti-asthmatic medication doses on the microhardness of enamel and microhardness, surface roughness and color of restorative materials. Methods: Human enamel samples and packable and flowable composite restorations were used. The samples were exposed to Salbutamol (0.6 mL/6 mL saline) and Budesonide (2 mL/2 mL saline) via a custom-made chamber connected to a nebulizer. Medication administration was conducted for 10 days. The samples were brushed with an electronic brush in a continuous and circular mode for 10 s after 10 min of medication administration. Assessments of microhardness, surface roughness and color were carried out at three different time intervals: baseline (T0), 5 days (T1) and 10 days (T2). One-way analysis of variance (ANOVA), a two-sample t-test and a Bonferroni multiple comparison test were used to analyze the data and compare between the groups. Results: Both medications significantly (p < 0.05) decreased the microhardness of the enamel and composite samples after 10 days. Both medications lowered the surface roughness of both types of composite with a greater effect observed after 10 days of Budesonide administration (p < 0.05). Both medications had comparable detectable color change on both types of composite with a greater effect observed after 10 days of Budesonide administration (p < 0.05). Conclusion: Salbutamol and Budesonide significantly decreased microhardness in the enamel samples. Both medications affected the properties of packable and flowable composites. The packable composite showed more resistance to microhardness changes. Both medications showed a clinically detectable change in the color of packable and flowable composites. Full article
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13 pages, 6307 KiB  
Article
Chemoselective Coatings of GL13K Antimicrobial Peptides for Dental Implants
by Isha Mutreja, Caixia Lan, Qishun Li and Conrado Aparicio
Pharmaceutics 2023, 15(10), 2418; https://doi.org/10.3390/pharmaceutics15102418 - 04 Oct 2023
Viewed by 858
Abstract
Dental implant−associated infection is a clinical challenge which poses a significant healthcare and socio−economic burden. To overcome this issue, developing antimicrobial surfaces, including antimicrobial peptide coatings, has gained great attention. Different physical and chemical routes have been used to obtain these biofunctional coatings, [...] Read more.
Dental implant−associated infection is a clinical challenge which poses a significant healthcare and socio−economic burden. To overcome this issue, developing antimicrobial surfaces, including antimicrobial peptide coatings, has gained great attention. Different physical and chemical routes have been used to obtain these biofunctional coatings, which in turn might have a direct influence on their bioactivity and functionality. In this study, we present a silane−based, fast, and efficient chemoselective conjugation of antimicrobial peptides (Cys−GL13K) to coat titanium implant surfaces. Comprehensive surface analysis was performed to confirm the surface functionalization of as−prepared and mechanically challenged coatings. The antibacterial potency of the evaluated surfaces was confirmed against both Streptococcus gordonii and Streptococcus mutans, the primary colonizers and pathogens of dental surfaces, as demonstrated by reduced bacteria viability. Additionally, human dental pulp stem cells demonstrated long−term viability when cultured on Cys−GL13K−grafted titanium surfaces. Cell functionality and antimicrobial capability against multi−species need to be studied further; however, our results confirmed that the proposed chemistry for chemoselective peptide anchoring is a valid alternative to traditional site−unspecific anchoring methods and offers opportunities to modify varying biomaterial surfaces to form potent bioactive coatings with multiple functionalities to prevent infection. Full article
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20 pages, 8343 KiB  
Article
The Effects of Thermocycling on the Physical Properties and Biocompatibilities of Various CAD/CAM Restorative Materials
by Se-Young Kim, Han-Jin Bae, Hae-Hyoung Lee, Jong-Hyuk Lee, Yu-Jin Kim, Yu-Sung Choi, Jung-Hwan Lee and Soo-Yeon Shin
Pharmaceutics 2023, 15(8), 2122; https://doi.org/10.3390/pharmaceutics15082122 - 10 Aug 2023
Cited by 2 | Viewed by 1175
Abstract
The purpose of this study is to evaluate the changes in physical properties and biocompatibilities caused by thermocycling of CAD/CAM restorative materials (lithium disilicate, zirconia reinforced lithium silicate, polymer-infiltrated ceramic network, resin nanoceramic, highly translucent zirconia). A total of 225 specimens were prepared [...] Read more.
The purpose of this study is to evaluate the changes in physical properties and biocompatibilities caused by thermocycling of CAD/CAM restorative materials (lithium disilicate, zirconia reinforced lithium silicate, polymer-infiltrated ceramic network, resin nanoceramic, highly translucent zirconia). A total of 225 specimens were prepared (12.0 × 10.0 × 1.5 mm) and divided into three groups subjected to water storage at 37 °C for 24 h (control group), 10,000 cycles in distilled water at 5–55 °C (first aged group), and 22,000 cycles in distilled water at 5–55 °C (second aged group) [(n= 15, each]). The nanoindentation hardness and Young’s modulus (nanoindenter), surface roughness (atomic force microscopy (AFM)), surface texture (scanning electron microscopy (FE-SEM)), elemental concentration (energy dispersive spectroscopy (EDS)) and contact angle were evaluated. The morphology, proliferation and adhesion of cultured human gingival fibroblasts (HGFs) were analyzed. The data were analyzed using one-way ANOVA and Tukey’s test (p < 0.05). The results showed that the nanoindentation hardness and Young’s modulus were decreased after thermocycling aging. Cell viability and proliferation of the material decreased with aging except for the highly translucent zirconia. Zirconia-reinforced lithium silicate exhibited significantly lower cell viability compared to other materials. The surface roughnesses of all groups increased with aging. Cell viability and Cell adhesion were influenced by various factors, including the surface chemical composition, hydrophilicity, surface roughness, and topography. Full article
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20 pages, 6234 KiB  
Article
Propolis as a Cariostatic Agent in Lozenges and Impact of Storage Conditions on the Stability of Propolis
by Anna Kurek-Górecka, Paweł Ramos, Małgorzata Kłósek, Elżbieta Bobela, Zenon P. Czuba, Radosław Balwierz and Paweł Olczyk
Pharmaceutics 2023, 15(6), 1768; https://doi.org/10.3390/pharmaceutics15061768 - 19 Jun 2023
Cited by 1 | Viewed by 1260
Abstract
Propolis is known as a source of compounds with strong antibacterial activity. Due to the antibacterial effect against streptococci of the oral cavity, it seems to be a useful agent in decreasing the accumulation of dental plaque. It is rich in polyphenols which [...] Read more.
Propolis is known as a source of compounds with strong antibacterial activity. Due to the antibacterial effect against streptococci of the oral cavity, it seems to be a useful agent in decreasing the accumulation of dental plaque. It is rich in polyphenols which are responsible for a beneficial impact on the oral microbiota and antibacterial effect. The aim of the study was to evaluate the antibacterial effect of Polish propolis against cariogenic bacteria. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined on cariogenic streptococci related to the occurrence of dental caries. Lozenges based on xylitol, glycerin, gelatin, water, and ethanol extract of propolis (EEP) were prepared. The effect of prepared lozenges on cariogenic bacteria was assessed. Propolis was compared to chlorhexidine which is used in dentistry as the gold standard. In addition, the prepared propolis formulation was stored under stress conditions to assess the influence of physical conditions (i.e., temperature, relative humidity, and UV radiation). In the experiment, thermal analyses were also performed to evaluate the compatibility of propolis with the substrate used to create the base of lozenges. The observed antibacterial effect of propolis and prepared lozenges with EEP may suggest directing subsequent research on prophylactic and therapeutic properties decreasing the accumulation of dental plaque. Therefore, it is worth highlighting that propolis may play an important role in the management of dental health and bring advantages in preventing periodontal diseases and caries as well as dental plaque. The colorimetric analyses carried out in the CIE L*a*b* system, microscopic examinations, and TGA/DTG/c-DTA measurements indicate the unfavorable effect of the tested storage conditions on the lozenges with propolis. This fact is particularly evident for lozenges stored under stress conditions, i.e., 40 °C/75% RH/14 days, and lozenges exposed to UVA radiation for 60 min. In addition, the obtained thermograms of the tested samples indicate the thermal compatibility of the ingredients used to create the formulation of lozenges. Full article
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12 pages, 1093 KiB  
Article
Antibacterial Activity of a Bioactive Tooth-Coating Material Containing Surface Pre-Reacted Glass in a Complex Multispecies Subgingival Biofilm
by Caio Junji Tanaka, José Augusto Rodrigues, João Marcos Spessoto Pingueiro, Tatiane Tiemi Macedo, Magda Feres, Jamil Awad Shibli and Bruno Bueno-Silva
Pharmaceutics 2023, 15(6), 1727; https://doi.org/10.3390/pharmaceutics15061727 - 14 Jun 2023
Cited by 1 | Viewed by 1114
Abstract
Bioactive materials were developed with the ability to release fluoride and provide some antimicrobial potential, to be widely used in dentistry today. However, few scientific studies have evaluated the antimicrobial activity of bioactive surface pre-reacted glass (S-PRG) coatings (PRG Barrier Coat, Shofu, Kyoto, [...] Read more.
Bioactive materials were developed with the ability to release fluoride and provide some antimicrobial potential, to be widely used in dentistry today. However, few scientific studies have evaluated the antimicrobial activity of bioactive surface pre-reacted glass (S-PRG) coatings (PRG Barrier Coat, Shofu, Kyoto, Japan) on periodontopathogenic biofilms. This study evaluated the antibacterial activity of S-PRG fillers on the microbial profile of multispecies subgingival biofilms. A Calgary Biofilm Device (CBD) was used to grow a 33-species biofilm related to periodontitis for 7 days. The S-PRG coating was applied on CBD pins from the test group and photo-activated (PRG Barrier Coat, Shofu), while the control group received no coating. Seven days after treatment, the total bacterial counts, metabolic activity, and microbial profile of the biofilms were observed using a colorimetric assay and DNA–DNA hybridization. Statistical analyses were applied; namely, the Mann–Whitney, Kruskal–Wallis, and Dunn’s post hoc tests. The bacterial activity of the test group was reduced by 25.7% compared with that of the control group. A statistically significant reduction was observed for the counts of 15 species: A. naeslundii, A. odontolyticus, V. parvula, C. ochracea, C. sputigena, E. corrodens, C. gracilis, F. nucleatum polymorphum, F. nucleatum vincentii, F. periodonticum, P. intermedia, P. gingivalis, G. morbillorum, S. anginosus, and S. noxia (p ≤ 0.05). The bioactive coating containing S-PRG modified the composition of the subgingival biofilm in vitro, thereby decreasing colonization by pathogens. Full article
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19 pages, 7505 KiB  
Article
Physicochemical, Biological, and Antibacterial Properties of Four Bioactive Calcium Silicate-Based Cements
by Yu-Ji Jang, Yu-Jin Kim, Huong Thu Vu, Jeong-Hui Park, Seong-Jin Shin, Khandmaa Dashnyam, Jonathan C. Knowles, Hae-Hyoung Lee, Soo-Kyung Jun, Mi-Ran Han, Joon-Haeng Lee, Jong-Soo Kim, Jong-Bin Kim, Jung-Hwan Lee and Ji-Sun Shin
Pharmaceutics 2023, 15(6), 1701; https://doi.org/10.3390/pharmaceutics15061701 - 09 Jun 2023
Cited by 2 | Viewed by 1053
Abstract
Calcium silicate-based cement (CSC) is a pharmaceutical agent that is widely used in dentistry. This bioactive material is used for vital pulp treatment due to its excellent biocompatibility, sealing ability, and antibacterial activity. Its drawbacks include a long setting time and poor maneuverability. [...] Read more.
Calcium silicate-based cement (CSC) is a pharmaceutical agent that is widely used in dentistry. This bioactive material is used for vital pulp treatment due to its excellent biocompatibility, sealing ability, and antibacterial activity. Its drawbacks include a long setting time and poor maneuverability. Hence, the clinical properties of CSC have recently been improved to decrease its setting time. Despite the widespread clinical usage of CSC, there is no research comparing recently developed CSCs. Therefore, the purpose of this study is to compare the physicochemical, biological, and antibacterial properties of four commercial CSCs: two powder–liquid mix types (RetroMTA® [RETM]; Endocem® MTA Zr [ECZR]) and two premixed types (Well-Root™ PT [WRPT]; Endocem® MTA premixed [ECPR]). Each sample was prepared using circular Teflon molds, and tests were conducted after 24 h of setting. The premixed CSCs exhibited a more uniform and less rough surface, higher flowability, and lower film thickness than the powder–liquid mix CSCs. In the pH test, all CSCs showed values between 11.5 and 12.5. In the biological test, cells exposed to ECZR at a concentration of 25% showed greater cell viability, but none of the samples showed a significant difference at low concentration (p > 0.05). Alkaline phosphatase staining revealed that cells exposed to ECZR underwent more odontoblast differentiation than the cells exposed to the other materials; however, no significant difference was observed at a concentration of 12.5% (p > 0.05). In the antibacterial test, the premixed CSCs showed better results than the powder–liquid mix CSCs, and ECPR yielded the best results, followed by WRPT. In conclusion, the premixed CSCs showed improved physical properties, and of the premixed types, ECPR exhibited the highest antibacterial properties. For biological properties, none of these materials showed significant differences at 12.5% dilution. Therefore, ECPR may be a promising material with high antibacterial activity among the four CSCs, but further investigation is needed for clinical situations. Full article
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13 pages, 5131 KiB  
Article
A Novel Control Method of Enterococcus faecalis by Co-Treatment with Protamine and Calcium Hydroxide
by Yu Abe and Michiyo Honda
Pharmaceutics 2023, 15(6), 1629; https://doi.org/10.3390/pharmaceutics15061629 - 31 May 2023
Viewed by 1231
Abstract
Enterococcus faecalis (E. faecalis), a gram-positive facultative anaerobic bacterium, is likely to survive root canal treatment because of its extremely high alkaline tolerance, which may contribute to the refractory nature of apical periodontitis (AP). In this study, protamine was combined with [...] Read more.
Enterococcus faecalis (E. faecalis), a gram-positive facultative anaerobic bacterium, is likely to survive root canal treatment because of its extremely high alkaline tolerance, which may contribute to the refractory nature of apical periodontitis (AP). In this study, protamine was combined with calcium hydroxide to evaluate its efficacy in killing E. faecalis. First, the antibacterial activity of protamine against E. faecalis was investigated. Protamine reduced the E. faecalis growth rate at concentrations above the MIC (250 μg/mL), but was not bactericidal at any of the concentrations tested. Next, we investigated the calcium hydroxide tolerance of E. faecalis, using a 10% 310 medium, adjusted for pH by adding a calcium hydroxide solution. The results showed that E. faecalis could survive and proliferate in alkaline environments up to pH 10. However, the complete killing of E. faecalis was observed when protamine (250 μg/mL) was added. In addition, compared with treatment with protamine and calcium hydroxide alone, membrane damage and internalization of protamine into the cytoplasm of E. faecalis were enhanced. Therefore, the synergistic increase in antibacterial activity may be related to the action of both antimicrobial agents on the cell membrane. In conclusion, co-treatment with protamine and calcium hydroxide seems to be very effective in sterilizing E. faecalis, and has the potential to provide a novel control method against E. faecalis for root canal treatment. Full article
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28 pages, 5028 KiB  
Article
Microporous/Macroporous Polycaprolactone Scaffolds for Dental Applications
by Tara Shabab, Onur Bas, Bronwin L. Dargaville, Akhilandeshwari Ravichandran, Phong A. Tran and Dietmar W. Hutmacher
Pharmaceutics 2023, 15(5), 1340; https://doi.org/10.3390/pharmaceutics15051340 - 26 Apr 2023
Cited by 2 | Viewed by 1639
Abstract
This study leverages the advantages of two fabrication techniques, namely, melt-extrusion-based 3D printing and porogen leaching, to develop multiphasic scaffolds with controllable properties essential for scaffold-guided dental tissue regeneration. Polycaprolactone–salt composites are 3D-printed and salt microparticles within the scaffold struts are leached out, [...] Read more.
This study leverages the advantages of two fabrication techniques, namely, melt-extrusion-based 3D printing and porogen leaching, to develop multiphasic scaffolds with controllable properties essential for scaffold-guided dental tissue regeneration. Polycaprolactone–salt composites are 3D-printed and salt microparticles within the scaffold struts are leached out, revealing a network of microporosity. Extensive characterization confirms that multiscale scaffolds are highly tuneable in terms of their mechanical properties, degradation kinetics, and surface morphology. It can be seen that the surface roughness of the polycaprolactone scaffolds (9.41 ± 3.01 µm) increases with porogen leaching and the use of larger porogens lead to higher roughness values, reaching 28.75 ± 7.48 µm. Multiscale scaffolds exhibit improved attachment and proliferation of 3T3 fibroblast cells as well as extracellular matrix production, compared with their single-scale counterparts (an approximate 1.5- to 2-fold increase in cellular viability and metabolic activity), suggesting that these structures could potentially lead to improved tissue regeneration due to their favourable and reproducible surface morphology. Finally, various scaffolds designed as a drug delivery device were explored by loading them with the antibiotic drug cefazolin. These studies show that by using a multiphasic scaffold design, a sustained drug release profile can be achieved. The combined results strongly support the further development of these scaffolds for dental tissue regeneration applications. Full article
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26 pages, 11693 KiB  
Article
Hydroxyapatite Thin Films of Marine Origin as Sustainable Candidates for Dental Implants
by Gabriela Dorcioman, Valentina Grumezescu, George E. Stan, Mariana Carmen Chifiriuc, Gratiela Pircalabioru Gradisteanu, Florin Miculescu, Elena Matei, Gianina Popescu-Pelin, Irina Zgura, Valentin Craciun, Faik Nüzhet Oktar and Liviu Duta
Pharmaceutics 2023, 15(4), 1294; https://doi.org/10.3390/pharmaceutics15041294 - 20 Apr 2023
Cited by 5 | Viewed by 1989
Abstract
Novel biomaterials with promising bone regeneration potential, derived from rich, renewable, and cheap sources, are reported. Thus, thin films were synthesized from marine-derived (i.e., from fish bones and seashells) hydroxyapatite (MdHA) by pulsed laser deposition (PLD) technique. Besides the physical–chemical and mechanical investigations, [...] Read more.
Novel biomaterials with promising bone regeneration potential, derived from rich, renewable, and cheap sources, are reported. Thus, thin films were synthesized from marine-derived (i.e., from fish bones and seashells) hydroxyapatite (MdHA) by pulsed laser deposition (PLD) technique. Besides the physical–chemical and mechanical investigations, the deposited thin films were also evaluated in vitro using dedicated cytocompatibility and antimicrobial assays. The morphological examination of MdHA films revealed the fabrication of rough surfaces, which were shown to favor good cell adhesion, and furthermore could foster the in-situ anchorage of implants. The strong hydrophilic behavior of the thin films was evidenced by contact angle (CA) measurements, with values in the range of 15–18°. The inferred bonding strength adherence values were superior (i.e., ~49 MPa) to the threshold established by ISO regulation for high-load implant coatings. After immersion in biological fluids, the growth of an apatite-based layer was noted, which indicated the good mineralization capacity of the MdHA films. All PLD films exhibited low cytotoxicity on osteoblast, fibroblast, and epithelial cells. Moreover, a persistent protective effect against bacterial and fungal colonization (i.e., 1- to 3-log reduction of E. coli, E. faecalis, and C. albicans growth) was demonstrated after 48 h of incubation, with respect to the Ti control. The good cytocompatibility and effective antimicrobial activity, along with the reduced fabrication costs from sustainable sources (available in large quantities), should, therefore, recommend the MdHA materials proposed herein as innovative and viable solutions for the development of novel coatings for metallic dental implants. Full article
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20 pages, 6064 KiB  
Article
Physicochemical, Pre-Clinical, and Biological Evaluation of Viscosity Optimized Sodium Iodide-Incorporated Paste
by Soo-Jin Chang, Yu-Jin Kim, Huong Thu Vu, Ji-Myung Choi, Jeong-Hui Park, Seong-Jin Shin, Khandmaa Dashnyam, Jonathan C. Knowles, Hae-Hyoung Lee, Soo-Kyung Jun, Mi-Ran Han, Joon-Haeng Lee, Jong-Soo Kim, Ji-Sun Shin, Jong-Bin Kim and Jung-Hwan Lee
Pharmaceutics 2023, 15(4), 1072; https://doi.org/10.3390/pharmaceutics15041072 - 27 Mar 2023
Viewed by 1540
Abstract
This study aimed to investigate the impact of different viscosities of silicone oil on the physicochemical, pre-clinical usability, and biological properties of a sodium iodide paste. Six different paste groups were created by mixing therapeutic molecules, sodium iodide (D30) and iodoform (I30), with [...] Read more.
This study aimed to investigate the impact of different viscosities of silicone oil on the physicochemical, pre-clinical usability, and biological properties of a sodium iodide paste. Six different paste groups were created by mixing therapeutic molecules, sodium iodide (D30) and iodoform (I30), with calcium hydroxide and one of the three different viscosities of silicone oil (high (H), medium (M), and low (L)). The study evaluated the performance of these groups, including I30H, I30M, I30L, D30H, D30M, and D30L, using multiple parameters such as flow, film thickness, pH, viscosity, and injectability, with statistical analysis (p < 0.05). Remarkably, the D30L group demonstrated superior outcomes compared to the conventional iodoform counterpart, including a significant reduction in osteoclast formation, as examined through TRAP, c-FOS, NFATc1, and Cathepsin K (p < 0.05). Additionally, mRNA sequencing showed that the I30L group exhibited increased expression of inflammatory genes with upregulated cytokines compared to the D30L group. These findings suggest that the optimized viscosity of the sodium iodide paste (D30L) may lead to clinically favorable outcomes, such as slower root resorption, when used in primary teeth. Overall, the results of this study suggest that the D30L group shows the most satisfactory outcomes, which may be a promising root-filling material that could replace conventional iodoform-based pastes. Full article
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14 pages, 1979 KiB  
Article
Prospects of Using Gum Arabic Silver Nanoparticles in Toothpaste to Prevent Dental Caries
by Omnia Abdelmoneim Khidir Ahmed, Nicole Remaliah Samantha Sibuyi, Adewale Oluwaseun Fadaka, Ernest Maboza, Annette Olivier, Abram Madimabe Madiehe, Mervin Meyer and Greta Geerts
Pharmaceutics 2023, 15(3), 871; https://doi.org/10.3390/pharmaceutics15030871 - 08 Mar 2023
Cited by 6 | Viewed by 1734
Abstract
There is growing interest in the use of green synthesized silver nanoparticles (AgNPs) to control and prevent dental diseases. The incorporation of green synthesized AgNPs into dentifrices to reduce pathogenic oral microbes is motivated by their presumed biocompatibility and broad-spectrum antimicrobial activity. In [...] Read more.
There is growing interest in the use of green synthesized silver nanoparticles (AgNPs) to control and prevent dental diseases. The incorporation of green synthesized AgNPs into dentifrices to reduce pathogenic oral microbes is motivated by their presumed biocompatibility and broad-spectrum antimicrobial activity. In the present study, gum arabic AgNPs (GA-AgNPs) were formulated into a toothpaste (TP) using a commercial TP at a non-active concentration, to produce GA-AgNPs_TP. The TP was selected after evaluating the antimicrobial activity of four commercial TPs 1-4 on selected oral microbes using agar disc diffusion and microdilution assays. The less active TP-1 was then used in the formulation of GA-AgNPs_TP-1; thereafter, the antimicrobial activity of GA-AgNPs_0.4g was compared to GA-AgNPs_TP-1. The cytotoxicity of GA-AgNPs_0.4g and GA-AgNPs_TP-1 was also assessed on the buccal mucosa fibroblast (BMF) cells using the MTT assay. The study demonstrated that antimicrobial activity of GA-AgNPs_0.4g was retained after being combined with a sub-lethal or inactive concentration of TP-1. The non-selective antimicrobial activity and cytotoxicity of both GA-AgNPs_0.4g and GA-AgNPs_TP-1 was demonstrated to be time and concentration dependent. These activities were instant, reducing microbial and BMF cell growth in less than one hour of exposure. However, the use of dentifrice commonly takes 2 min and rinsed off thereafter, which could prevent damage to the oral mucosa. Although, GA-AgNPs_TP-1 has a good prospect as a TP or oral healthcare product, more studies are required to further improve the biocompatibility of this formulation. Full article
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20 pages, 5163 KiB  
Article
Acceleration of Wound Healing through Amorphous Calcium Carbonate, Stabilized with High-Energy Polyphosphate
by Shunfeng Wang, Meik Neufurth, Hadrian Schepler, Rongwei Tan, Zhending She, Bilal Al-Nawas, Xiaohong Wang, Heinz C. Schröder and Werner E. G. Müller
Pharmaceutics 2023, 15(2), 494; https://doi.org/10.3390/pharmaceutics15020494 - 02 Feb 2023
Cited by 3 | Viewed by 1635
Abstract
Amorphous calcium carbonate (ACC), precipitated in the presence of inorganic polyphosphate (polyP), has shown promise as a material for bone regeneration due to its morphogenetic and metabolic energy (ATP)-delivering properties. The latter activity of the polyP-stabilized ACC (“ACC∙PP”) particles is associated with the [...] Read more.
Amorphous calcium carbonate (ACC), precipitated in the presence of inorganic polyphosphate (polyP), has shown promise as a material for bone regeneration due to its morphogenetic and metabolic energy (ATP)-delivering properties. The latter activity of the polyP-stabilized ACC (“ACC∙PP”) particles is associated with the enzymatic degradation of polyP, resulting in the transformation of ACC into crystalline polymorphs. In a novel approach, stimulated by these results, it was examined whether “ACC∙PP” also promotes the healing of skin injuries, especially chronic wounds. In in vitro experiments, “ACC∙PP” significantly stimulated the migration of endothelial cells, both in tube formation and scratch assays (by 2- to 3-fold). Support came from ex vivo experiments showing increased cell outgrowth in human skin explants. The transformation of ACC into insoluble calcite was suppressed by protein/serum being present in wound fluid. The results were confirmed in vivo in studies on normal (C57BL/6) and diabetic (db/db) mice. Topical administration of “ACC∙PP” significantly accelerated the rate of re-epithelialization, particularly in delayed healing wounds in diabetic mice (day 7: 1.5-fold; and day 13: 1.9-fold), in parallel with increased formation/maturation of granulation tissue. The results suggest that administration of “ACC∙PP” opens a new strategy to improve ATP-dependent wound healing, particularly in chronic wounds. Full article
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20 pages, 3431 KiB  
Article
New Insights into the In Vitro Antioxidant Routes and Osteogenic Properties of Sr/Zn Phytate Compounds
by Gerardo Asensio, Marcela Martín-del-Campo, Rosa Ana Ramírez, Luis Rojo and Blanca Vázquez-Lasa
Pharmaceutics 2023, 15(2), 339; https://doi.org/10.3390/pharmaceutics15020339 - 19 Jan 2023
Cited by 4 | Viewed by 1434
Abstract
Sr/Zn phytate compounds have been shown interest in biomaterial science, specifically in dental implantology, due to their antimicrobial effects against Streptococcus mutans and their capacity to form bioactive coatings. Phytic acid is a natural chelating compound that shows antioxidant and osteogenic properties that can [...] Read more.
Sr/Zn phytate compounds have been shown interest in biomaterial science, specifically in dental implantology, due to their antimicrobial effects against Streptococcus mutans and their capacity to form bioactive coatings. Phytic acid is a natural chelating compound that shows antioxidant and osteogenic properties that can play an important role in bone remodelling processes affected by oxidative stress environments, such as those produced during infections. The application of non-protein cell-signalling molecules that regulate both bone and ROS homeostasis is a promising strategy for the regeneration of bone tissues affected by oxidative stress processes. In this context, phytic acid (PA) emerged as an excellent option since its antioxidant and osteogenic properties can play an important role in bone remodelling processes. In this study, we explored the antioxidant and osteogenic properties of two metallic PA complexes bearing bioactive cations, i.e., Sr2+ (SrPhy) and Zn2+ (ZnPhy), highlighting the effect of the divalent cations anchored to phytate moieties and their capability to modulate the PA properties. The in vitro features of the complexes were analyzed and compared with those of their precursor PA. The ferrozine/FeCl2 method indicated that SrPhy exhibited a more remarkable ferrous ion affinity than ZnPhy, while the antioxidant activity demonstrated by a DPPH assay showed that only ZnPhy reduced the content of free radicals. Likewise, the antioxidant potential was assessed with RAW264.7 cell cultures. An ROS assay indicated again that ZnPhy was the only one to reduce the ROS content (20%), whereas all phytate compounds inhibited lipid peroxidation following the decreasing order of PA > SrPhy > ZnPhy. The in vitro evaluation of the phytate’s osteogenic ability was performed using hMSC cells. The results showed tailored properties related to the cation bound in each complex. ZnPhy overexpressed ALP activity at 3 and 14 days, and SrPhy significantly increased calcium deposition after 21 days. This study demonstrated that Sr/Zn phytates maintained the antioxidant and osteogenic properties of PA and can be used in bone regenerative therapies involving oxidative environments, such as infected implant coatings and periodontal tissues. Full article
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18 pages, 4934 KiB  
Article
Antibacterial and Proliferative Effects of NaOH-Coated Titanium, Zirconia, and Ceramic-Reinforced PEEK Dental Composites on Bone Marrow Mesenchymal Stem Cells
by Artiom Lijnev, Jeevithan Elango, Vicente M. Gómez-López, Carlos Pérez-Albacete Martínez, José Manuel Granero Marín and José Eduardo Maté Sánchez De Val
Pharmaceutics 2023, 15(1), 98; https://doi.org/10.3390/pharmaceutics15010098 - 28 Dec 2022
Cited by 7 | Viewed by 4201
Abstract
Several metallic and polymer-based implants have been fabricated for orthopedic applications. For instance, titanium (Ti), zirconia (Zr), and polyetheretherketone (PEEK) are employed due to their excellent biocompatibility properties. Hence, the present study aimed to compare the functional and biological properties of these three [...] Read more.
Several metallic and polymer-based implants have been fabricated for orthopedic applications. For instance, titanium (Ti), zirconia (Zr), and polyetheretherketone (PEEK) are employed due to their excellent biocompatibility properties. Hence, the present study aimed to compare the functional and biological properties of these three biomaterials with surface modification. For this purpose, Ti, Zr, and ceramic-reinforced PEEK (CrPEEK) were coated with NaOH and tested for the biological response. Our results showed that the surface modification of these biomaterials significantly improved the water contact, protein adhesion, and bioactivity compared with uncoated samples. Among the NaOH-coated biomaterials, Ti and CrPEEK showed higher protein absorption than Zr. However, the mineral binding ability was higher in CrPEEK than in the other two biomaterials. Although the coating improved the functional properties, NaOH coating did not influence the antibacterial effect against E. coli and S. aureus in these biomaterials. Similar to the antibacterial effects, the NaOH coating did not contribute any significant changes in cell proliferation and cell loading, and CrPEEK showed better biocompatibility among the biomaterials. Therefore, this study concluded that the surface modification of biomaterials could potentially improve the functional properties but not the antibacterial and biocompatibility, and CrPEEK could be an alternative material to Ti and Zr with desirable qualities in orthopedic applications. Full article
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13 pages, 2579 KiB  
Article
Are Endodontic Solvents Cytotoxic? An In Vitro Study on Human Periodontal Ligament Stem Cells
by José Luis Sanz, Sergio López-García, Leopoldo Forner, Francisco Javier Rodríguez-Lozano, David García-Bernal, Sonia Sánchez-Bautista, Clara Puig-Herreros, Vicent Rosell-Clari and Ricardo E. Oñate-Sánchez
Pharmaceutics 2022, 14(11), 2415; https://doi.org/10.3390/pharmaceutics14112415 - 08 Nov 2022
Cited by 2 | Viewed by 1742
Abstract
The aim of this study was to assess the influence of eucalyptol, chloroform, and Endosolv on the proliferative capability, cell viability, and migration rates of human periodontal ligament stem cells (hPDLSCs) in vitro. Solvent eluates were formulated following ISO 10993-5 guidelines, and 1%, [...] Read more.
The aim of this study was to assess the influence of eucalyptol, chloroform, and Endosolv on the proliferative capability, cell viability, and migration rates of human periodontal ligament stem cells (hPDLSCs) in vitro. Solvent eluates were formulated following ISO 10993-5 guidelines, and 1%, 0.25%, and 0.1% dilutions were prepared. The HPDLSCs were isolated from the extracted third molars of healthy donors. The following parameters were assessed: cell viability via trypan blue and IC50 assays, cell migration via horizontal wound healing assay, cell morphology via cell cytoskeleton staining (phalloidin labeling), and cell oxidative stress via reactive oxygen species assay. The data were analyzed using one-way ANOVA and Tukey’s posthoc tests, and their significance was established at p < 0.05. Chloroform and eucalyptol exhibited significantly higher cytotoxicity on the hPDLSCs in vitro compared to the control group, as shown by the cell viability, migration, morphology, and reactive oxygen species release assays. Alternatively, Endosolv showed adequate cytotoxicity levels comparable to those of the control group. The cytotoxicity of the tested endodontic solvents increased in a dose-dependent manner. The results from the present study highlight the cytotoxicity of chloroform and eucalyptol. Thus, their limited and cautious use is recommended, avoiding solvent extrusion. Full article
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14 pages, 4686 KiB  
Article
Controlled Release of Bone Morphogenetic Protein-2 Augments the Coupling of Angiogenesis and Osteogenesis for Accelerating Mandibular Defect Repair
by Hao Yao, Jiaxin Guo, Wangyong Zhu, Yuxiong Su, Wenxue Tong, Lizhen Zheng, Liang Chang, Xinluan Wang, Yuxiao Lai, Ling Qin and Jiankun Xu
Pharmaceutics 2022, 14(11), 2397; https://doi.org/10.3390/pharmaceutics14112397 - 07 Nov 2022
Cited by 8 | Viewed by 1987
Abstract
Reconstruction of a mandibular defect is challenging, with high expectations for both functional and esthetic results. Bone morphogenetic protein-2 (BMP-2) is an essential growth factor in osteogenesis, but the efficacy of the BMP-2-based strategy on the bone regeneration of mandibular defects has not [...] Read more.
Reconstruction of a mandibular defect is challenging, with high expectations for both functional and esthetic results. Bone morphogenetic protein-2 (BMP-2) is an essential growth factor in osteogenesis, but the efficacy of the BMP-2-based strategy on the bone regeneration of mandibular defects has not been well-investigated. In addition, the underlying mechanisms of BMP-2 that drives the bone formation in mandibular defects remain to be clarified. Here, we utilized BMP-2-loaded hydrogel to augment bone formation in a critical-size mandibular defect model in rats. We found that implantation of BMP-2-loaded hydrogel significantly promoted intramembranous ossification within the defect. The region with new bone triggered by BMP-2 harbored abundant CD31+ endomucin+ type H vessels and associated osterix (Osx)+ osteoprogenitor cells. Intriguingly, the new bone comprised large numbers of skeletal stem cells (SSCs) (CD51+ CD200+) and their multi-potent descendants (CD51+ CD105+), which were mainly distributed adjacent to the invaded blood vessels, after implantation of the BMP-2-loaded hydrogel. Meanwhile, BMP-2 further elevated the fraction of CD51+ CD105+ SSC descendants. Overall, the evidence indicates that BMP-2 may recapitulate a close interaction between functional vessels and SSCs. We conclude that BMP-2 augmented coupling of angiogenesis and osteogenesis in a novel and indispensable way to improve bone regeneration in mandibular defects, and warrants clinical investigation and application. Full article
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13 pages, 3462 KiB  
Article
Biological Evaluation of the Effect of Root Canal Sealers Using a Rat Model
by Motoki Okamoto, Sayako Matsumoto, Kiichi Moriyama, Hailing Huang, Masakatsu Watanabe, Jiro Miura, Keita Sugiyama, Yujiro Hirose, Manabu Mizuhira, Nanako Kuriki, Julian G. Leprince, Yusuke Takahashi, Shigetada Kawabata and Mikako Hayashi
Pharmaceutics 2022, 14(10), 2038; https://doi.org/10.3390/pharmaceutics14102038 - 24 Sep 2022
Cited by 5 | Viewed by 1998
Abstract
Gutta-percha points and root canal sealers have been used for decades in endodontics for root canal obturation. With techniques such as single cone methods, the amount of sealer is larger, making their properties more critical. However, relatively few reports have comprehensively evaluated their [...] Read more.
Gutta-percha points and root canal sealers have been used for decades in endodontics for root canal obturation. With techniques such as single cone methods, the amount of sealer is larger, making their properties more critical. However, relatively few reports have comprehensively evaluated their biological effects. To this end, we evaluated three types of sealers, zinc oxide-fatty acid-, bio-glass- and methacrylate resin-containing sealers were considered. Their biological effects were evaluated using a rat subcutaneous implantation model. Each sealer was loaded inside a Teflon tube and implanted subcutaneously in the backs of rats. Inflammatory cells were observed around all samples 7 days after implantation and reduced after 28 days. Our results revealed that all samples were in contact with the subcutaneous tissue surrounding the sealer. Additionally, Ca and P accumulation was observed in only the bio-glass-containing sealer. Furthermore, each of the three sealers exhibited unique immune and inflammatory modulatory effects. In particular, bio-glass and methacrylate resin sealers were found to induce variable gene expression in adjacent subcutaneous tissues related to angiogenesis, wound healing, muscle tissue, and surrounding subcutaneous tissue. These results may help to understand the biological impacts of root canal sealers on surrounding biological tissues, guiding future research and comparisons with new generations of materials. Full article
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15 pages, 22529 KiB  
Article
Premixed Calcium Silicate-Based Root Canal Sealer Reinforced with Bioactive Glass Nanoparticles to Improve Biological Properties
by Min-Kyung Jung, So-Chung Park, Yu-Jin Kim, Jong-Tae Park, Jonathan C. Knowles, Jeong-Hui Park, Khandmaa Dashnyam, Soo-Kyung Jun, Hae-Hyoung Lee and Jung-Hwan Lee
Pharmaceutics 2022, 14(9), 1903; https://doi.org/10.3390/pharmaceutics14091903 - 08 Sep 2022
Cited by 7 | Viewed by 2452
Abstract
Recently, bioactive glass nanoparticles (BGns) have been acknowledged for their ability to promote interactions with the periapical tissue and enhance tissue regeneration by releasing therapeutic ions. However, there have been no studies on calcium silicate sealers with bioactive glass nanoparticle (BGn) additives. In [...] Read more.
Recently, bioactive glass nanoparticles (BGns) have been acknowledged for their ability to promote interactions with the periapical tissue and enhance tissue regeneration by releasing therapeutic ions. However, there have been no studies on calcium silicate sealers with bioactive glass nanoparticle (BGn) additives. In the present study, a premixed calcium silicate root canal sealer reinforced with BGn (pre-mixed-RCS@BGn) was developed and its physicochemical features and biological effects were analyzed. Three specimens were in the trial: 0%, 0.5%, and 1% bioactive glass nanoparticles (BGns) were gradually added to the premixed type of calcium silicate-based sealer (pre-mixed-RCS). To elucidate the surface properties, scanning electron microscopy, X-ray diffraction, and energy-dispersive spectroscopy were used and flowability, setting time, solubility, and radiopacity were analyzed to evaluate the physical properties. Chemical properties were investigated by water contact angle, pH change, and ion release measurements. The antibacterial effects of the bioactive set sealers were tested with Enterococcus faecalis and the viability of human bone marrow-derived mesenchymal stem cells (hMSCs) with this biomaterial was examined. In addition, osteogenic differentiation was highly stimulated, which was confirmed by ALP (Alkaline phosphatase) activity and the ARS (Alizarin red S) staining of hMSCs. The pre-mixed-RCS@BGn satisfied the ISO standards for root canal sealers and maintained antimicrobial activity. Moreover, pre-mixed-RCS@BGn with more BGns turned out to have less cytotoxicity than pre-mixed-RCS without BGns while promoting osteogenic differentiation, mainly due to calcium and silicon ion release. Our results suggest that BGns enhance the biological properties of this calcium silicate-based sealer and that the newly introduced pre-mixed-RCS@BGn has the capability to be applied in dental procedures as a root canal sealer. Further studies focusing more on the biocompatibility of pre-mixed-RCS@BGn should be performed to investigate in vivo systems, including pulp tissue. Full article
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17 pages, 5617 KiB  
Article
Dexamethasone and Doxycycline Doped Nanoparticles Increase the Differentiation Potential of Human Bone Marrow Stem Cells
by Manuel Toledano-Osorio, Sergio López-García, Raquel Osorio, Manuel Toledano, David García-Bernal, Sonia Sánchez-Bautista and Francisco Javier Rodríguez-Lozano
Pharmaceutics 2022, 14(9), 1865; https://doi.org/10.3390/pharmaceutics14091865 - 04 Sep 2022
Cited by 6 | Viewed by 1663
Abstract
Non-resorbable polymeric nanoparticles (NPs) are proposed as an adjunctive treatment for bone regenerative strategies. The present in vitro investigation aimed to evaluate the effect of the different prototypes of bioactive NPs loaded with zinc (Zn-NPs), doxycycline (Dox-NPs) or dexamethasone (Dex-NPs) on the viability, [...] Read more.
Non-resorbable polymeric nanoparticles (NPs) are proposed as an adjunctive treatment for bone regenerative strategies. The present in vitro investigation aimed to evaluate the effect of the different prototypes of bioactive NPs loaded with zinc (Zn-NPs), doxycycline (Dox-NPs) or dexamethasone (Dex-NPs) on the viability, morphology, migration, adhesion, osteoblastic differentiation, and mineralization potential of human bone marrow stem cells (hBMMSCs). Cell viability, proliferation, and differentiation were assessed using a resaruzin-based assay, cell cycle analysis, cell migration evaluation, cell cytoskeleton staining analysis, Alizarin Red S staining, and expression of the osteogenic-related genes by a real-time quantitative polymerase chain reaction (RT-qPCR). One-Way ANOVA and Tukey’s test were employed. The resazurin assay showed adequate cell viability considering all concentrations and types of NPs at 24, 48, and 72 h of culture. The cell cycle analysis revealed a regular cell cycle profile at 0.1, 1, and 10 µg/mL, whereas 100 µg/mL produced an arrest of cells in the S phase. Cells cultured with 0.1 and 1 µg/mL NP concentrations showed a similar migration capacity to the untreated group. After 21 days, mineralization was increased by all the NPs prototypes. Dox-NPs and Dex-NPs produced a generalized up-regulation of the osteogenic-related genes. Dex-NPs and Dox-NPs exhibited excellent osteogenic potential and promoted hBMMSC differentiation. Future investigations, both in vitro and in vivo, are required to confirm the suitability of these NPs for their clinical application. Full article
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16 pages, 2473 KiB  
Article
Effect of Exo/Endogenous Prophylaxis Dentifrice/Drug and Cariogenic Conditions of Patient on Molecular Property of Dental Biofilm: Synchrotron FTIR Spectroscopic Study
by Pavel Seredin, Dmitry Goloshchapov, Vladimir Kashkarov, Dmitry Nesterov, Yuri Ippolitov, Ivan Ippolitov and Jitraporn Vongsvivut
Pharmaceutics 2022, 14(7), 1355; https://doi.org/10.3390/pharmaceutics14071355 - 26 Jun 2022
Cited by 4 | Viewed by 2038
Abstract
(1) Objectives: This study is the first one to investigate the molecular composition of the dental biofilm during the exogenous and endogenous prophylaxis stages (use of dentifrice/drug) of individuals with different cariogenic conditions using molecular spectroscopy methods. (2) Materials and Methods: The study [...] Read more.
(1) Objectives: This study is the first one to investigate the molecular composition of the dental biofilm during the exogenous and endogenous prophylaxis stages (use of dentifrice/drug) of individuals with different cariogenic conditions using molecular spectroscopy methods. (2) Materials and Methods: The study involved 100 participants (50 males and 50 females), aged 18–25 years with different caries conditions. Biofilm samples were collected from the teeth surface of all participants. The molecular composition of biofilms was investigated using synchrotron infrared microspectroscopy. Changes in the molecular composition were studied through calculation and analysis of ratios between organic and mineral components of biofilm samples. (3) Results: Based on the data obtained by synchrotron FTIR, calculations of organic and mineral component ratios, and statistical analysis of the data, we were able to assess changes occurring in the molecular composition of the dental biofilm. Variations in the phosphate/protein/lipid, phosphate/mineral, and phospholipid/lipid ratios and the presence of statistically significant intra- and inter-group differences in these ratios indicate that the mechanisms of ion adsorption, compounds and complexes arriving from oral fluid into dental biofilm during exo/endogenous prophylaxis, differ for patients in norm and caries development. (4) Conclusions: The conformational environment and charge interaction in the microbiota and the electrostatic state of the biofilm protein network in patients with different cariogenic conditions play an important role. (5) Clinical Significance: Understanding the changes that occur in the molecular composition of the dental biofilm in different oral homeostasis conditions will enable successful transition to a personalised approach in dentistry and high-tech healthcare. Full article
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Review

Jump to: Research

15 pages, 2537 KiB  
Review
Cyclodextrins as Multi-Functional Ingredients in Dentistry
by Susana Santos Braga
Pharmaceutics 2023, 15(9), 2251; https://doi.org/10.3390/pharmaceutics15092251 - 31 Aug 2023
Cited by 3 | Viewed by 1145
Abstract
Cyclodextrins are present in a variety of oral hygiene compositions. The present work describes the role of cyclodextrins in several toothpastes and mouthwashes that are already available in the market, as well as their prospective use in other applications as investigated in studies [...] Read more.
Cyclodextrins are present in a variety of oral hygiene compositions. The present work describes the role of cyclodextrins in several toothpastes and mouthwashes that are already available in the market, as well as their prospective use in other applications as investigated in studies in the literature. Moreover, cyclodextrins are under study for the development of materials used in various techniques of dental repair, such as fillings, cements and binders therein. Their role in each of the innovative materials is presented. Finally, the prospect of the use of cyclodextrin-based delivery systems for the oral cavity is introduced, with a focus on new cyclodextrin molecules with dual action as bone-targeting agents and osteogenic drugs, and on new cross-linked cyclodextrin particles with a high drug loading and sustained drug delivery profile for the treatment of diseases that require prolonged action, such as periodontitis. In conclusion, cyclodextrins are herein demonstrated to act as versatile and multi-action ingredients with a broad range of applications in dentistry. Full article
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22 pages, 1922 KiB  
Review
pH-Responsive Biomaterials for the Treatment of Dental Caries—A Focussed and Critical Review
by Yanping He, Krasimir Vasilev and Peter Zilm
Pharmaceutics 2023, 15(7), 1837; https://doi.org/10.3390/pharmaceutics15071837 - 27 Jun 2023
Cited by 5 | Viewed by 1654
Abstract
Dental caries is a common and costly multifactorial biofilm disease caused by cariogenic bacteria that ferment carbohydrates to lactic acid, demineralizing the inorganic component of teeth. Therefore, low pH (pH 4.5) is a characteristic signal of the localised carious environment, compared to a [...] Read more.
Dental caries is a common and costly multifactorial biofilm disease caused by cariogenic bacteria that ferment carbohydrates to lactic acid, demineralizing the inorganic component of teeth. Therefore, low pH (pH 4.5) is a characteristic signal of the localised carious environment, compared to a healthy oral pH range (6.8 to 7.4). The development of pH-responsive delivery systems that release antibacterial agents in response to low pH has gained attention as a targeted therapy for dental caries. Release is triggered by high levels of acidogenic species and their reduction may select for the establishment of health-associated biofilm communities. Moreover, drug efficacy can be amplified by the modification of the delivery system to target adhesion to the plaque biofilm to extend the retention time of antimicrobial agents in the oral cavity. In this review, recent developments of different pH-responsive nanocarriers and their biofilm targeting mechanisms are discussed. This review critically discusses the current state of the art and innovations in the development and use of smart delivery materials for dental caries treatment. The authors’ views for the future of the field are also presented. Full article
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24 pages, 11108 KiB  
Review
Extracellular Vesicles for Dental Pulp and Periodontal Regeneration
by Hongbin Lai, Jiaqi Li, Xiaoxing Kou, Xueli Mao, Wei Zhao and Lan Ma
Pharmaceutics 2023, 15(1), 282; https://doi.org/10.3390/pharmaceutics15010282 - 14 Jan 2023
Cited by 9 | Viewed by 2058
Abstract
Extracellular vesicles (EVs) are lipid bound particles derived from their original cells, which play critical roles in intercellular communication through their cargoes, including protein, lipids, and nucleic acids. According to their biogenesis and release pathway, EVs can be divided into three categories: apoptotic [...] Read more.
Extracellular vesicles (EVs) are lipid bound particles derived from their original cells, which play critical roles in intercellular communication through their cargoes, including protein, lipids, and nucleic acids. According to their biogenesis and release pathway, EVs can be divided into three categories: apoptotic vesicles (ApoVs), microvesicles (MVs), and small EVs (sEVs). Recently, the role of EVs in oral disease has received close attention. In this review, the main characteristics of EVs are described, including their classification, biogenesis, biomarkers, and components. Moreover, the therapeutic mechanism of EVs in tissue regeneration is discussed. We further summarize the current status of EVs in pulp/periodontal tissue regeneration and discuss the potential mechanisms. The therapeutic potential of EVs in pulp and periodontal regeneration might involve the promotion of tissue regeneration and immunomodulatory capabilities. Furthermore, we highlight the current challenges in the translational use of EVs. This review would provide valuable insights into the potential therapeutic strategies of EVs in dental pulp and periodontal regeneration. Full article
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20 pages, 910 KiB  
Review
Creating a Microenvironment to Give Wings to Dental Pulp Regeneration—Bioactive Scaffolds
by Nan Hu, Weiping Li, Wentao Jiang, Jin Wen and Shensheng Gu
Pharmaceutics 2023, 15(1), 158; https://doi.org/10.3390/pharmaceutics15010158 - 03 Jan 2023
Cited by 1 | Viewed by 1798
Abstract
Dental pulp and periapical diseases make patients suffer from acute pain and economic loss. Although root canal therapies, as demonstrated through evidence-based medicine, can relieve symptoms and are commonly employed by dentists, it is still difficult to fully restore a dental pulp’s nutrition, [...] Read more.
Dental pulp and periapical diseases make patients suffer from acute pain and economic loss. Although root canal therapies, as demonstrated through evidence-based medicine, can relieve symptoms and are commonly employed by dentists, it is still difficult to fully restore a dental pulp’s nutrition, sensory, and immune-regulation functions. In recent years, researchers have made significant progress in tissue engineering to regenerate dental pulp in a desired microenvironment. With breakthroughs in regenerative medicine and material science, bioactive scaffolds play a pivotal role in creating a suitable microenvironment for cell survival, proliferation, and differentiation, following dental restoration and regeneration. This article focuses on current challenges and novel perspectives about bioactive scaffolds in creating a microenvironment to promote dental pulp regeneration. We hope our readers will gain a deeper understanding and new inspiration of dental pulp regeneration through our summary. Full article
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16 pages, 2281 KiB  
Review
Functional Hydrogels and Their Applications in Craniomaxillofacial Bone Regeneration
by Yi Yu, Tingting Yu, Xing Wang and Dawei Liu
Pharmaceutics 2023, 15(1), 150; https://doi.org/10.3390/pharmaceutics15010150 - 31 Dec 2022
Cited by 7 | Viewed by 1636
Abstract
Craniomaxillofacial bone defects are characterized by an irregular shape, bacterial and inflammatory environment, aesthetic requirements, and the need for the functional recovery of oral–maxillofacial areas. Conventional clinical treatments are currently unable to achieve high-quality craniomaxillofacial bone regeneration. Hydrogels are a class of multifunctional [...] Read more.
Craniomaxillofacial bone defects are characterized by an irregular shape, bacterial and inflammatory environment, aesthetic requirements, and the need for the functional recovery of oral–maxillofacial areas. Conventional clinical treatments are currently unable to achieve high-quality craniomaxillofacial bone regeneration. Hydrogels are a class of multifunctional platforms made of polymers cross-linked with high water content, good biocompatibility, and adjustable physicochemical properties for the intelligent delivery of goods. These characteristics make hydrogel systems a bright prospect for clinical applications in craniomaxillofacial bone. In this review, we briefly demonstrate the properties of hydrogel systems that can come into effect in the field of bone regeneration. In addition, we summarize the hydrogel systems that have been developed for craniomaxillofacial bone regeneration in recent years. Finally, we also discuss the prospects in the field of craniomaxillofacial bone tissue engineering; these discussions can serve as an inspiration for future hydrogel design. Full article
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17 pages, 2706 KiB  
Review
Treated Dentin Matrix in Tissue Regeneration: Recent Advances
by Fei Bi, Zhijun Zhang and Weihua Guo
Pharmaceutics 2023, 15(1), 91; https://doi.org/10.3390/pharmaceutics15010091 - 27 Dec 2022
Cited by 2 | Viewed by 1805
Abstract
Tissue engineering is a new therapeutic strategy used to repair serious damage caused by trauma, a tumor or other major diseases, either for vital organs or tissues sited in the oral cavity. Scaffold materials are an indispensable part of this. As an extracellular-matrix-based [...] Read more.
Tissue engineering is a new therapeutic strategy used to repair serious damage caused by trauma, a tumor or other major diseases, either for vital organs or tissues sited in the oral cavity. Scaffold materials are an indispensable part of this. As an extracellular-matrix-based bio-material, treated dentin matrixes have become promising tissue engineering scaffolds due to their unique natural structure, astonishing biological induction activity and benign bio-compatibility. Furthermore, it is important to note that besides its high bio-activity, a treated dentin matrix can also serve as a carrier and release controller for drug molecules and bio-active agents to contribute to tissue regeneration and immunomodulation processes. This paper describes the research advances of treated dentin matrixes in tissue regeneration from the aspects of its vital properties, biologically inductive abilities and application explorations. Furthermore, we present the concerning challenges of signaling mechanisms, source extension, individualized 3D printing and drug delivery system construction during our investigation into the treated dentin matrix. This paper is expected to provide a reference for further research on treated dentin matrixes in tissue regeneration and better promote the development of relevant disease treatment approaches. Full article
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22 pages, 2762 KiB  
Review
Alternative Antibiotics in Dentistry: Antimicrobial Peptides
by Alexandra Griffith, Akilah Mateen, Kenneth Markowitz, Steven R. Singer, Carla Cugini, Emi Shimizu, Gregory R. Wiedman and Vivek Kumar
Pharmaceutics 2022, 14(8), 1679; https://doi.org/10.3390/pharmaceutics14081679 - 12 Aug 2022
Cited by 13 | Viewed by 3018
Abstract
The rise of antibiotic resistant bacteria due to overuse and misuse of antibiotics in medicine and dentistry is a growing concern. New approaches are needed to combat antibiotic resistant (AR) bacterial infections. There are a number of methods available and in development to [...] Read more.
The rise of antibiotic resistant bacteria due to overuse and misuse of antibiotics in medicine and dentistry is a growing concern. New approaches are needed to combat antibiotic resistant (AR) bacterial infections. There are a number of methods available and in development to address AR infections. Dentists conventionally use chemicals such as chlorohexidine and calcium hydroxide to kill oral bacteria, with many groups recently developing more biocompatible antimicrobial peptides (AMPs) for use in the oral cavity. AMPs are promising candidates in the treatment of (oral) infections. Also known as host defense peptides, AMPs have been isolated from animals across all kingdoms of life and play an integral role in the innate immunity of both prokaryotic and eukaryotic organisms by responding to pathogens. Despite progress over the last four decades, there are only a few AMPs approved for clinical use. This review summarizes an Introduction to Oral Microbiome and Oral Infections, Traditional Antibiotics and Alternatives & Antimicrobial Peptides. There is a focus on cationic AMP characteristics and mechanisms of actions, and an overview of animal-derived natural and synthetic AMPs, as well as observed microbial resistance. Full article
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