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Open AccessArticle

A Novel Control Method of Enterococcus faecalis by Co-Treatment with Protamine and Calcium Hydroxide

by

Yu Abe

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Michiyo Honda

Pharmaceutics 2023, 15(6), 1629; https://doi.org/10.3390/pharmaceutics15061629 - 31 May 2023

Viewed by 236

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

μ

g/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

μ

g/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

(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research)

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Open AccessArticle

Microporous/Macroporous Polycaprolactone Scaffolds for Dental Applications

by

Tara Shabab

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Onur Bas

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Bronwin L. Dargaville

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Akhilandeshwari Ravichandran

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Phong A. Tran

and

Dietmar W. Hutmacher

Pharmaceutics 2023, 15(5), 1340; https://doi.org/10.3390/pharmaceutics15051340 - 26 Apr 2023

Viewed by 606

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

(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research)

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Open AccessArticle

Hydroxyapatite Thin Films of Marine Origin as Sustainable Candidates for Dental Implants

by

Gabriela Dorcioman

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Valentina Grumezescu

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George E. Stan

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Mariana Carmen Chifiriuc

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Gratiela Pircalabioru Gradisteanu

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Florin Miculescu

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Elena Matei

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Gianina Popescu-Pelin

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Pharmaceutics 2023, 15(4), 1294; https://doi.org/10.3390/pharmaceutics15041294 - 20 Apr 2023

Viewed by 872

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

(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research)

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Open AccessArticle

Physicochemical, Pre-Clinical, and Biological Evaluation of Viscosity Optimized Sodium Iodide-Incorporated Paste

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Pharmaceutics 2023, 15(4), 1072; https://doi.org/10.3390/pharmaceutics15041072 - 27 Mar 2023

Viewed by 651

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

(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research)

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Open AccessArticle

Prospects of Using Gum Arabic Silver Nanoparticles in Toothpaste to Prevent Dental Caries

by

Omnia Abdelmoneim Khidir Ahmed

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Nicole Remaliah Samantha Sibuyi

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Adewale Oluwaseun Fadaka

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Ernest Maboza

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Annette Olivier

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Abram Madimabe Madiehe

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Mervin Meyer

and

Greta Geerts

Pharmaceutics 2023, 15(3), 871; https://doi.org/10.3390/pharmaceutics15030871 - 08 Mar 2023

Viewed by 612

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

(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research)

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Open AccessArticle

Acceleration of Wound Healing through Amorphous Calcium Carbonate, Stabilized with High-Energy Polyphosphate

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Pharmaceutics 2023, 15(2), 494; https://doi.org/10.3390/pharmaceutics15020494 - 02 Feb 2023

Viewed by 777

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

(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research)

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Open AccessArticle

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 2 | Viewed by 790

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

(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research)

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Open AccessArticle

Antibacterial and Proliferative Effects of NaOH-Coated Titanium, Zirconia, and Ceramic-Reinforced PEEK Dental Composites on Bone Marrow Mesenchymal Stem Cells

by

Artiom Lijnev

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Jeevithan Elango

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Vicente M. Gómez-López

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Carlos Pérez-Albacete Martínez

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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

Viewed by 1037

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

(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research)

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Open AccessArticle

Are Endodontic Solvents Cytotoxic? An In Vitro Study on Human Periodontal Ligament Stem Cells

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José Luis Sanz

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Sergio López-García

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Leopoldo Forner

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Francisco Javier Rodríguez-Lozano

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David García-Bernal

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Sonia Sánchez-Bautista

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Clara Puig-Herreros

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Vicent Rosell-Clari

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Ricardo E. Oñate-Sánchez

Pharmaceutics 2022, 14(11), 2415; https://doi.org/10.3390/pharmaceutics14112415 - 08 Nov 2022

Viewed by 982

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

(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research)

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Open AccessArticle

Controlled Release of Bone Morphogenetic Protein-2 Augments the Coupling of Angiogenesis and Osteogenesis for Accelerating Mandibular Defect Repair

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Pharmaceutics 2022, 14(11), 2397; https://doi.org/10.3390/pharmaceutics14112397 - 07 Nov 2022

Cited by 4 | Viewed by 1282

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

(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research)

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Open AccessArticle

Biological Evaluation of the Effect of Root Canal Sealers Using a Rat Model

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Pharmaceutics 2022, 14(10), 2038; https://doi.org/10.3390/pharmaceutics14102038 - 24 Sep 2022

Cited by 1 | Viewed by 1122

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

(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research)

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Open AccessArticle

Premixed Calcium Silicate-Based Root Canal Sealer Reinforced with Bioactive Glass Nanoparticles to Improve Biological Properties

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Pharmaceutics 2022, 14(9), 1903; https://doi.org/10.3390/pharmaceutics14091903 - 08 Sep 2022

Cited by 1 | Viewed by 1494

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

(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research)

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Open AccessArticle

Dexamethasone and Doxycycline Doped Nanoparticles Increase the Differentiation Potential of Human Bone Marrow Stem Cells

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Manuel Toledano-Osorio

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Sonia Sánchez-Bautista

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Francisco Javier Rodríguez-Lozano

Pharmaceutics 2022, 14(9), 1865; https://doi.org/10.3390/pharmaceutics14091865 - 04 Sep 2022

Cited by 3 | Viewed by 1029

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

(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research)

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Open AccessArticle

Effect of Exo/Endogenous Prophylaxis Dentifrice/Drug and Cariogenic Conditions of Patient on Molecular Property of Dental Biofilm: Synchrotron FTIR Spectroscopic Study

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Pharmaceutics 2022, 14(7), 1355; https://doi.org/10.3390/pharmaceutics14071355 - 26 Jun 2022

Cited by 2 | Viewed by 1331

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

(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research)

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Review

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Open AccessReview

Extracellular Vesicles for Dental Pulp and Periodontal Regeneration

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Pharmaceutics 2023, 15(1), 282; https://doi.org/10.3390/pharmaceutics15010282 - 14 Jan 2023

Cited by 1 | Viewed by 933

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

(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research)

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Open AccessReview

Creating a Microenvironment to Give Wings to Dental Pulp Regeneration—Bioactive Scaffolds

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Pharmaceutics 2023, 15(1), 158; https://doi.org/10.3390/pharmaceutics15010158 - 03 Jan 2023

Viewed by 905

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

(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research)

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Open AccessReview

Functional Hydrogels and Their Applications in Craniomaxillofacial Bone Regeneration

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Pharmaceutics 2023, 15(1), 150; https://doi.org/10.3390/pharmaceutics15010150 - 31 Dec 2022

Viewed by 973

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

(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research)

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Open AccessReview

Treated Dentin Matrix in Tissue Regeneration: Recent Advances

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Fei Bi

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Zhijun Zhang

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Weihua Guo

Pharmaceutics 2023, 15(1), 91; https://doi.org/10.3390/pharmaceutics15010091 - 27 Dec 2022

Viewed by 928

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

(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research)

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Open AccessReview

Alternative Antibiotics in Dentistry: Antimicrobial Peptides

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Pharmaceutics 2022, 14(8), 1679; https://doi.org/10.3390/pharmaceutics14081679 - 12 Aug 2022

Cited by 6 | Viewed by 1750

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

(This article belongs to the Special Issue Biomaterials and Agents: Pharmaceutical and Biomedical Applications in Dental Research)

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