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The evolutionary establishment of an internal biological clock is a primordial event tightly associated with a 24‐h period. Changes in the circadian rhythm can affect cellular functions, including proliferation, DNA repair and redox state. Even isolated organs, tissues and cells can maintain an autonomous circadian rhythm. These cell‐autonomous molecular mechanisms are driven by intracellular clock genes, such as BMAL1. Little is known about the role of core clock genes and epigenetic modifications in the skin. Our focus was to identify BMAL1‐driven epigenetic modifications associated with gene transcription by mapping the acetylation landscape of histones in epithelial cells responding to injury. We explored the role of BMAL1 in epidermal wound and tissue regeneration using a loss‐of‐function approach in vivo. We worked with BMAL1 knockout mice and a contraction‐resistance wound healing protocol, determining the histone modifications using specific antibodies to detect the acetylation levels of histones H3 and H4. We found significant differences in the acetylation levels of histones in both homeostatic and injured skin with deregulated BMAL1. The intact skin displayed varied acetylation levels of histones H3 and H4, including hyperacetylation of H3 Lys 9 (H3K9). The most pronounced changes were observed at the repair site, with notable alterations in the acetylation pattern of histone H4. These findings reveal the importance of histone modifications in response to injury and indicate that modulation of BMAL1 and its associated epigenetic events could be therapeutically harnessed to improve skin regeneration. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of this study was to investigate the effect of aluminosilicate clay nanotubes (Halloysite, HNT) incorporated into the adhesive resin of a commercially available three-step etch and rinse bonding system (Adper Scotchbond Multi-Purpose/SBMP) on dentin bond strength, as well as the effect on several key physicochemical properties of the modified adhesive. Methods: Experimental adhesives were prepared by adding five distinct HNT amounts (5–30wt.%) into the adhesive resin (w/v) of the SBMP dentin bonding system. Bond strength to human dentin, microhardness, and degree of conversion (DC) of the modified adhesives were assessed. Results: From the shear bond strength data, it was determined that HNT incorporation at a concentration of 30wt.% resulted in the highest bond strength to dentin that was statistically significant (p =0.025) when compared to the control. Even though a significant increase in microhardness (p <0.001) was seen for the 30wt.% HNT-incorporated group, a significantly lower DC (p <0.001) was recorded when compared to the control. Significance: It was concluded that HNT can be incorporated up to 20wt.% without jeopardizing important physicochemical properties of the adhesive. The modification of the SBMP dentin bonding agent with 20wt.% HNT appears to hold great potential toward contributing to a durable dentin bond; not only from the possibility of strengthening the bond interface, but also due to HNT intrinsic capability of encapsulating therapeutic agents such as matrix metalloproteinase (MMP) inhibitors. [Copyright &y& Elsevier]

Abstract: Periodontitis is a major chronic inflammatory disorder that can lead to the destruction of the periodontal tissues and, ultimately, tooth loss. To date, flap debridement and/or flap curettage and periodontal regenerative therapy with membranes and bone grafting materials have been employed with distinct levels of clinical success. Current resorbable and non-resorbable membranes act as a physical barrier to avoid connective and epithelial tissue down-growth into the defect, favoring the regeneration of periodontal tissues. These conventional membranes possess many structural, mechanical, and bio-functional limitations and the “ideal” membrane for use in periodontal regenerative therapy has yet to be developed. Based on a graded-biomaterials approach, we have hypothesized that the next-generation of guided tissue and guided bone regeneration (GTR/GBR) membranes for periodontal tissue engineering will be a biologically active, spatially designed and functionally graded nanofibrous biomaterial that closely mimics the native extra-cellular matrix (ECM). Objective: This review is presented in three major parts, including (1) a brief overview of the periodontium and its pathological conditions, (2) currently employed therapeutics used to regenerate the distinct periodontal tissues, and (3) a review of commercially available GTR/GBR membranes as well as the recent advances on the processing and characterization of GTR/GBR membranes from a materials perspective. Significance: Studies of spatially designed and functionally graded membranes (FGM) and in vitro antibacterial/cell-related research are addressed. Finally, as a future outlook, the use of hydrogels in combination with scaffold materials is highlighted as a promising approach for periodontal tissue engineering. [Copyright &y& Elsevier]

Abstract: Objectives: To test the effect of rehydration time over the range prescribed in the manufacturer''s protocol on (1) the biomechanical properties and on (2) the recovery and stabilization of the collagenous matrix of AlloDerm®. Methods: A sterile dish containing warm saline solution was prepared, and samples rehydrated for 5min. Subsequently, three other dishes with the solution were prepared and samples assigned into three groups according to the total rehydration time: 10min (G1), 20min (G2), and 40min (G3). Uni-axial tensile testing was used to assess the biomechanical properties of the different groups and the control (dry condition). Physico-chemical properties were examined by Fourier transform infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC) as a function of rehydration time. Results: ANOVA revealed a significant change in tensile strength (p =0.0269) and in elastic modulus (p =0.0306) for AlloDerm following different rehydration times. The lowest tensile strength was in the dry condition, whereas the highest was achieved after a 40min rehydration. The shortest rehydration periods did not result in a statistically significant (p >0.05) change in elastic modulus. However, after 40min the elastic modulus increased significantly when compared to the shortest periods. FT-IR confirmed the protein backbone recovery of the graft matrix after rehydration. DSC scans of rehydrated samples showed visible shifts in the denaturation temperature to higher values compared to as-received sample (dry) suggesting stronger polymer–water bridge formation, supporting the increase in the biomechanical properties. Significance: The current study suggests that there are major changes on the biomechanical properties of the collagenous graft as rehydration time increases, which were also structurally confirmed by the physico-chemical analyses. Clinicians must be aware that the rehydration times of the manufacturer''s protocol result in a significant range in mechanical and physico-chemical properties. Therefore, a rehydration time of at least 20min guarantees not only better handling and mechanical properties but, most importantly, supplies a material that closely resembles the natural tissue. [Copyright &y& Elsevier]

Abstract: Objectives: (1) To synthesize 3mol% yttria-stabilized zirconia (3Y-TZP) powders via coprecipitation route, (2) to obtain zirconia ceramic specimens, analyze surface characteristics, and mechanical properties, and (3) to compare the processed material with three reinforced dental ceramics. Methods: A coprecipitation route was used to synthesize a 3mol% yttria-stabilized zirconia ceramic processed by uniaxial compaction and pressureless sintering. Commercially available alumina or alumina/zirconia ceramics, namely Procera AllCeram (PA), In-Ceram Zirconia Block (CAZ) and In-Ceram Zirconia (IZ) were chosen for comparison. All specimens (6mm×5mm×5mm) were polished and ultrasonically cleaned. Qualitative phase analysis was performed by XRD and apparent densities were measured on the basis of Archimedes principle. Ceramics were also characterized using SEM, TEM and EDS. The hardness measurements were made employing Vickers hardness test. Fracture toughness (K IC) was calculated. Data were analyzed using one-way analysis of variance (ANOVA) and Tukey''s test (α =0.05). Results: ANOVA revealed that the Vickers hardness (p <0.0001) and fracture toughness (p <0.0001) were affected by the ceramic materials composition. It was confirmed that the PA ceramic was constituted of a rhombohedral alumina matrix, so-called α-alumina. Both CAZ and IZ ceramics presented tetragonal zirconia and α-alumina mixture of phases. The SEM/EDS analysis confirmed the presence of aluminum in PA ceramic. In the IZ and CAZ ceramics aluminum, zirconium and cerium in grains involved by a second phase containing aluminum, silicon and lanthanum were identified. PA showed significantly higher mean Vickers hardness values (H V) (18.4±0.5GPa) compared to vitreous CAZ (10.3±0.2GPa) and IZ (10.6±0.4GPa) ceramics. Experimental Y-TZP showed significantly lower results than that of the other monophased ceramic (PA) (p <0.05) but it showed significantly higher fracture toughness (6.0±0.2MPam1/2) values when compared to the other tested ceramics (p <0.05). Significance: The coprecipitation method used to synthesize zirconia powders and the adopted ceramic processing conditions led to ceramics with mechanical properties comparable to commercially available reinforced ceramic materials. [Copyright &y& Elsevier]

Abstract: Objectives: Titanium alloys are considered the material of choice when used as endosteal part of implants. However, they are not able to bond directly to bone. The objective of this study was to suggest a chemical surface treatment for Ti–13Nb–13Zr to initiate the formation of hydroxy carbonated apatite (HCA) during in vitro bioactivity tests in simulated body fluid (SBF). Methods: Titanium, niobium, and zirconium hydride powders were blended, compacted and sintered. Sintered Ti–13Nb–13Zr samples were etched in HCl, H3PO4, and in a mixture of HF+HNO3, respectively, and subsequently pretreated in NaOH. The influence of acid etching conditions on the microstructure of the Ti–13Nb–13Zr alloys as well as on the rate of HCA formation was evaluated using SEM-EDS, FTIR, and gravimetric analyses. Results: Sintered Ti–13Nb–13Zr alloys consist of a Widmannstätten (α+β) microstructure. Exposure of chemically etched and NaOH activated samples to SBF for 1 week leads to the formation of a HCA layer on the surface of HCl as well as H3PO4 treated samples. No HCA formation was found on HNO3 treated samples. After 2 weeks in SBF the mass increase, that can be correlated to the HCA formation rate, was the highest for HCl pretreated samples (2.4mg/cm2) followed by H3PO4 (0.8mg/cm2) and HNO3 pretreated ones (0.2mg/cm2). Significance: Since the in vitro HCA formation from SBF is generally accepted as a typical feature for bioactive materials, it is supposed that HCl etching with subsequent NaOH treatment might enhance the in vivo bone-bonding ability of Ti–13Nb–13Zr. [Copyright &y& Elsevier]

Background Objectives Methods Results Discussion Conclusions Bibliometric analysis is a critical indicator of the influence and relevance of scientific papers, whilst also highlighting key contributors and gaps in knowledge in a scientific field.To update and analyse the 100 most‐cited papers in regenerative endodontics from 2019 to 2023.A search of the most‐cited recent papers focusing on regenerative endodontics using journals included in the category, ‘Dentistry, Oral Surgery & Medicine’, in the Clarivate Web of Science database from 2019 to 2023 was performed. Three researchers conducted the study selection and data extraction. Data extraction included publication title and year, authors, number and mean number of citations, institution, country and continent, study design, journal title, keywords and research topic. Citation counts were also collected in Google Scholar and Scopus databases. Graphical bibliometric networks were created using VOSviewer software.The number of citations of the 100 most‐cited articles ranged from 6 to 85. Most were published in 2020 (n = 48), principally in the Journal of Endodontics (47%), followed by International Endodontic Journal (13%), Journal of Dental Research (6%) and Dental Materials (6%). Laboratory study was the most common study design amongst the included papers (n = 47), followed by narrative reviews (n = 17) and observational studies (n = 16). The most frequent first author on the top three most‐cited papers was Hacer Aksel, whilst Adham A. Azim (n = 6; 89 citations) contributed most to the top 100 articles. The institution from which most articles originated was the University of Hong Kong (China) (n = 5; 81 citations), whereas the corresponding authors were predominantly from the United States of America (USA) (n = 31; 560 citations). The VOSviewer map of co‐authorship demonstrated research collaborative clusters. ‘Regenerative endodontics’ and ‘stem‐cells’ were the most employed keywords (37 and 36 occurrences respectively).The current study was designed not only to showcase the most influential papers in regenerative endodontics since 2019 but also to provide a better understanding of global research in this area over the last five years.This bibliometric analysis highlighted papers, authors, institutions and keywords in regenerative endodontics. The 100 most‐cited papers primarily consisted of laboratory studies published in the USA, focusing on evaluating biomaterials and scaffold design strategies in contact with stem cells. Clinical studies and systematic reviews representing higher levels of scientific evidence are currently not the most influential in the regenerative endodontic field. [ABSTRACT FROM AUTHOR]

Customization and the production of patient-specific devices, tailoring the unique anatomy of each patient's jaw and facial structures, are the new frontiers in dentistry and maxillofacial surgery. As a technological advancement, additive manufacturing has been applied to produce customized objects based on 3D computerized models. Therefore, this paper presents advances in additive manufacturing strategies for patient-specific devices in diverse dental specialties. This paper overviews current 3D printing techniques to fabricate dental and maxillofacial devices. Then, the most recent literature (2018–2023) available in scientific databases reporting advances in 3D-printed patient-specific devices for dental and maxillofacial applications is critically discussed, focusing on the major outcomes, material-related details, and potential clinical advantages. The recent application of 3D-printed customized devices in oral prosthodontics, implantology and maxillofacial surgery, periodontics, orthodontics, and endodontics are presented. Moreover, the potential application of 4D printing as an advanced manufacturing technology and the challenges and future perspectives for additive manufacturing in the dental and maxillofacial area are reported. Additive manufacturing techniques have been designed to benefit several areas of dentistry, and the technologies, materials, and devices continue to be optimized. Image-based and accurately printed patient-specific devices to replace, repair, and regenerate dental and maxillofacial structures hold significant potential to maximize the standard of care in dentistry. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the incorporation of halloysite nanotubes (HNTs) loaded with one of two calcium sources (i.e., calcium hydroxide/CaOH2 or beta-tricalcium phosphate/β-TCP) on the physicochemical and biological properties of an experimental resin-based dual-cured endodontic sealer. Materials and methods: HNTs were encapsulated with CaOH2 or β-TCP at 10 wt.%. HNTs containing CaOH2 or β-TCP were added into the experimental sealers at 50 wt.%. The control sealers were the calcium-free HNT-modified resin-based experimental sealer and AH Plus™, a commercially available endodontic sealer. Degree of conversion, setting time, flow, film thickness, radiopacity, dimensional stability, and calcium ions release were determined. Antibiofilm properties and cytocompatibility of the formulated sealers and commercial control were also evaluated. One and two-way ANOVA analysis followed by Tukey's post hoc test was conducted to evaluate the effect of the independent variable on the evaluated properties. Results: FTIR confirmed the encapsulation of calcium sources into HNTs. Regarding flow and film thickness, the values obtained from these sealers were in accordance with the specifications provided by ISO 6876. For radiopacity, AH Plus™ achieved the highest radiopacity (p<0.05). Among the experimental formulations, all experimental HNT-containing compositions exhibited values below 3 mm Al. The experimental sealers showed greater dimensional changes when compared to the commercial (AH Plus™) control. The release of calcium ions was observed for the HNT_CaOH2 and HNT_β-TCP sealers without statistical differences. Experimental sealers containing HNT_CaOH2 and HNT_β-TCP significantly reduced the CFU/mL count and showed cell compatibility. Conclusions: The findings of this study demonstrate that the incorporation of HNT_CaOH2 or HNT_β-TCP into resin-based experimental sealers promoted antimicrobial effects and gradual calcium release without impairing cytocompatibility or physicochemical properties of the sealers. Still, an adjustment to reach the minimal radiopacity established by ISO 6876 is needed. Clinical relevance: The experimental resin-based sealers seemed to be an alternative for endodontics. The incorporation of calcium sources exerts promising antimicrobial effects while displaying low cell toxicity. [ABSTRACT FROM AUTHOR]

The current standard for treating irreversibly damaged dental pulp is root canal therapy, which involves complete removal and debridement of the pulp space and filling with an inert biomaterial. A regenerative approach to treating diseased dental pulp may allow for complete healing of the native tooth structure and enhance the long-term outcome of once-necrotic teeth. The aim of this paper is, therefore, to highlight the current state of dental pulp tissue engineering and immunomodulatory biomaterials properties, identifying exciting opportunities for their synergy in developing next-generation biomaterials-driven technologies. An overview of the inflammatory process focusing on immune responses of the dental pulp, followed by periapical and periodontal tissue inflammation are elaborated. Then, the most recent advances in treating infection-induced inflammatory oral diseases, focusing on biocompatible materials with immunomodulatory properties are discussed. Of note, we highlight some of the most used modifications in biomaterials' surface, or content/drug incorporation focused on immunomodulation based on an extensive literature search over the last decade. We provide the readers with a critical summary of recent advances in immunomodulation related to pulpal, periapical, and periodontal diseases while bringing light to tissue engineering strategies focusing on healing and regenerating multiple tissue types. Significant advances have been made in developing biomaterials that take advantage of the host's immune system to guide a specific regenerative outcome. Biomaterials that efficiently and predictably modulate cells in the dental pulp complex hold significant clinical promise for improving standards of care compared to endodontic root canal therapy. [Display omitted] • Immunomodulatory biomaterials represent the next-generation dental pulp treatment. • M1 to M2 macrophage phenotype shift is vital for dental pulp healing/regeneration. • Biomaterials design is a crucial aspect of manipulating macrophage phenotype. [ABSTRACT FROM AUTHOR]

Degradation of the collagen fibrils at the dentin–resin interface by the enzymatic activity of matrix metalloproteinases (MMPs) has been known to permit some dental restoration complications, such as microleakage, secondary caries, and, ultimately, restoration failures. This study aimed to evaluate a modified adhesive by adding an MMP inhibitor from green tea extract with and without nanotube encapsulation to sustain the drug release. Epigallocatechin-3-gallate (EGCG) and Halloysite nanotubes (HNTs) were prepared to produce three variant combinations of modified adhesive (EGCG, EGCG-encapsulated HNT, and EGCG-free HNT). The drug loading efficiency and EGCG release over time were evaluated using UV-vis spectrometry. MMP-mediated β-casein (BCN) cleavage rate assays were used to determine the ability of the EGCG in eluates of the adhesive to inhibit MMP-9 activities. For up to 8 weeks, HNT encapsulation reduced release to a statistically significant level. MMP-mediated β-casein cleavage rate assays showed a significant decrease for the EGCG groups compared to the non-EGCG adhesive groups. Furthermore, the use of HNT for EGCG encapsulation to modify a dental adhesive helped slow down the rate of EGCG release without impacting its MMP inhibitory capabilities, which may help to maintain the dentin–resin interface's integrity over the long term after dental restoration placement. [ABSTRACT FROM AUTHOR]

This study was aimed at engineering photocrosslinkable azithromycin (AZ)-laden gelatin methacryloyl fibers via electrospinning to serve as a localized and biodegradable drug delivery system for endodontic infection control. AZ at three distinct amounts was mixed with solubilized gelatin methacryloyl and the photoinitiator to obtain the following fibers: GelMA+5%AZ, GelMA+10%AZ, and GelMA+15%AZ. Fiber morphology, diameter, AZ incorporation, mechanical properties, degradation profile, and antimicrobial action against Aggregatibacter actinomycetemcomitans and Actinomyces naeslundii were also studied. In vitro compatibility with human-derived dental pulp stem cells and inflammatory response in vivo using a subcutaneous rat model were also determined. A bead-free fibrous microstructure with interconnected pores was observed for all groups. GelMA and GelMA+10%AZ had the highest fiber diameter means. The tensile strength of the GelMA-based fibers was reduced upon AZ addition. A similar pattern was observed for the degradation profile in vitro. GelMA+15%AZ fibers led to the highest bacterial inhibition. The presence of AZ, regardless of the concentration, did not pose significant toxicity. In vivo findings indicated higher blood vessel formation, mild inflammation, and mature and thick well-oriented collagen fibers interweaving with the engineered fibers. Altogether, AZ-laden photocrosslinkable GelMA fibers had adequate mechanical and degradation properties, with 15%AZ displaying significant antimicrobial activity without compromising biocompatibility. [ABSTRACT FROM AUTHOR]

Electrospun scaffolds are a versatile biomaterial platform to mimic fibrillar structure of native tissues extracellular matrix, and facilitate the incorporation of biomolecules for regenerative therapies. Self-assembling peptide P 11 -4 has emerged as a promising strategy to induce mineralization; however, P 11 -4 application has been mostly addressed for early caries lesions repair on dental enamel. Here, to investigate P 11 -4′s efficacy on bone regeneration, polymeric electrospun scaffolds were developed, and then distinct concentrations of P 11 -4 were physically adsorbed on the scaffolds. P 11 -4-laden and pristine (P 11 -4-free) electrospun scaffolds were immersed in simulated body fluid and mineral precipitation identified by SEM. Functional groups and crystalline phases were analyzed by FTIR and XRD, respectively. Cytocompatibility, mineralization, and gene expression assays were conducted using stem cells from human exfoliated deciduous teeth. To investigate P 11 -4-laden scaffolds potential to induce in vivo mineralization, an established rat calvaria critical-size defect model was used. Results. We successfully synthesized nanofibrous (∼ 500 nm fiber diameter) scaffolds and observed that functionalization with P 11 -4 did not affect the fibers' diameter. SEM images indicated mineral precipitation, while FTIR and XRD confirmed apatite-like formation and crystallization for P 11 -4-laden scaffolds. In addition, P 11 -4-laden scaffolds were cytocompatible, highly stimulated cell-mediated mineral deposition, and upregulated the expression of mineralization-related genes compared to pristine scaffolds. P 11 -4-laden scaffolds led to enhanced in vivo bone regeneration after 8 weeks compared to pristine PCL. Electrospun scaffolds functionalized with P 11 -4 are a promising strategy for inducing mineralized tissues regeneration in the craniomaxillofacial complex. [Display omitted] • Self-assembly peptide P 11 -4-laden scaffolds induces mineral precipitation. • P 11 -4-laden scaffolds stimulate stem cells to mineral deposition. • P 11 -4-laden scaffolds upregulate osteogenic markers. • P 11 -4-laden scaffolds induces bone formation in vivo. [ABSTRACT FROM AUTHOR]

This work sought to formulate photocrosslinkable chlorhexidine (CHX)-laden methacrylated gelatin (CHX/GelMA) hydrogels with broad spectrum of action against endodontic pathogens as a clinically viable cell-friendly disinfection therapy prior to regenerative endodontics procedures. CHX/GelMA hydrogel formulations were successfully synthesized using CHX concentrations between 0.12 % and 5 % w/v. Hydrogel microstructure was evaluated by scanning electron microscopy (SEM). Swelling and enzymatic degradation were assessed to determine microenvironmental effects. Compression test was performed to investigate the influence of CHX incorporation on the hydrogels' biomechanics. The antimicrobial and anti-biofilm potential of the formulated hydrogels were assessed using agar diffusion assays and a microcosms biofilm model, respectively. The cytocompatibility was evaluated by exposing stem cells from human exfoliated deciduous teeth (SHEDs) to hydrogel extracts (i.e. , leachable byproducts obtained from overtime hydrogel incubation in phosphate buffer saline). The data were analyzed using One- and Two-way ANOVA and Tukey's test (α = 0.05). CHX/GelMA hydrogels were effectively prepared. NMR spectroscopy confirmed the incorporation of CHX into GelMA. The addition of CHX did not change the micromorphology (pore size) nor the swelling profile (p > 0.05). CHX incorporation reduced the degradation rate of the hydrogels (p < 0.001); whereas, it contributed to increased compressive modulus (p < 0.05). Regarding the antimicrobial properties, the incorporation of CHX showed a statistically significant decrease in the number of bacteria colonies at 0.12 % and 0.5 % concentration (p < 0.001) and completely inhibited the growth of biofilm at concentration levels 1 %, 2 %, and 5 %. Meanwhile, the addition of CHX, regardless of the concentration, did not lead to cell toxicity, as cell viability values were above 70 %. The addition of CHX into GelMA showed significant antimicrobial action against the pathogens tested, even at low concentrations, with the potential to be used as a cell-friendly injectable drug delivery system for root canal disinfection prior to regenerative endodontics. [Display omitted] • Chlorhexidine-laden gelatin methacrylate hydrogel (CHX/GelMA) was synthesized. • CHX/GelMA showed significant antimicrobial action against endodontic pathogens. • CHX/GelMA holds potential for infection eradication prior to regenerative procedures. [ABSTRACT FROM AUTHOR]

Objective A combination of antibiotics, including but not limited to metronidazole (MET) and ciprofloxacin (CIP), has been indicated to eradicate bacteria in necrotic immature permanent teeth prior to regenerative procedures. It has been shown clinically that antibiotic pastes may lead to substantial stem cell death. The aim of this study was to synthesise scaffolds containing various concentrations of CIP to enhance cell viability while preserving antimicrobial properties . Design Polydioxanone (PDS)-based electrospun scaffolds were processed with decreasing CIP concentrations (25–1 wt.%) and morphologically evaluated using scanning electron microscopy (SEM). Cytotoxicity assays were performed to determine whether the amount of CIP released from the scaffolds would lead to human dental pulp stem cell (hDPSC) toxicity. Similarly, WST-1 assays were performed to evaluate the impact of CIP release on hDPSC proliferation. Pure PDS scaffolds and saturated double antibiotic solution MET/CIP (DAP) served as both positive and negative controls, respectively. Antibacterial efficacy against E. faecalis ( Ef ) was tested. Results A significant decrease in hDPSC’ viability at concentrations 5–25 wt.% was observed. However, concentrations below 5 wt.% did not impair cell viability. Data from the WST-1 assays indicated no detrimental impact on cell proliferation for scaffolds containing 2.5 wt.% CIP or less. Significant antimicrobial properties were seen for CIP-scaffolds at lower concentrations ( i.e. , 1 and 2.5 wt.%). Conclusion The obtained data demonstrated that a reduced concentration of CIP incorporated into PDS-based scaffolds maintains its antimicrobial properties while enhancing viability and proliferation of dental pulp stem cells. [ABSTRACT FROM AUTHOR]

Background: The effects of ethylenediaminetetraacetic acid (EDTA) on regenerative endodontic procedures (REPs) are controversial, because, despite releasing growth factors from dentine, some studies show negative effects on cell behaviour. Objectives: The aim of the study was to investigate the influence of the use of EDTA in REP on the growth factors' release, cell behaviour and tissue regeneration. Methods: A systematic search was conducted (PubMed/Medline, Scopus, Cochrane Library, Web of Science, Embase, OpenGrey and reference lists) up to February 2021. Only in vivo and in vitro studies evaluating the effects of EDTA on the biological factors of dentine, pulp/periapical tissues and cell behaviour were eligible. Studies without a control group or available full text were excluded. The growth factors' release was the primary outcome. Risk of bias in the in vitro and in vivo studies was performed according to Joanna Briggs Institute's Checklist and SYRCLE's RoB tool, respectively. Results: Of the 1848 articles retrieved, 36 were selected. Amongst these, 32 were in vitro, three animal studies and one with both models. The EDTA concentrations ranged from 3% to 15%, at different times. Regarding growth factors' release (17 studies), 15 studies found significant transforming growth factor (TGF)‐β release after dentine conditioning with EDTA, and most found no influence on vascular endothelial growth factor release. Regarding cell behaviour (26 studies), eight studies showed no influence of EDTA‐treated dentine on cell viability, whereas, five, nine and six studies showed higher cell migration, adhesion and differentiation respectively. No influence of EDTA conditioning was observed in animal studies. In vitro studies had a low risk of bias, whereas animal studies had high risk of bias. Meta‐analysis was unfeasible. Discussion: This review found that EDTA increased TGF‐β release and improved cell activity. However, well‐designed histological analyses using immature teeth models are needed. Conclusions: High‐quality in vitro evidence suggests that EDTA‐treated dentine positively influences TGF‐β release, cell migration, attachment and differentiation; further research to evaluate its influence on tissue regeneration is necessary due to low methodological quality of the animal studies. [ABSTRACT FROM AUTHOR]

From a materials perspective, the pillars for the development of clinically translatable scaffold-based strategies for craniomaxillofacial (CMF) bone and periodontal regeneration have included electrospinning and 3D printing (biofabrication) technologies. Here, we offer a detailed analysis of the latest innovations in 3D (bio)printing strategies for CMF bone and periodontal regeneration and provide future directions envisioning the development of advanced 3D architectures for successful clinical translation. First, the principles of electrospinning applied to the generation of biodegradable scaffolds are discussed. Next, we present on extrusion-based 3D printing technologies with a focus on creating scaffolds with improved regenerative capacity. In addition, we offer a critical appraisal on 3D (bio)printing and multitechnology convergence to enable the reconstruction of CMF bones and periodontal tissues. As a future outlook, we highlight future directions associated with the utilisation of complementary biomaterials and (bio)fabrication technologies for effective translation of personalised and functional scaffolds into the clinics. [ABSTRACT FROM AUTHOR]

Alveolar bone defects can be highly variable in their morphology and, as the defect size increases, they become more challenging to treat with currently available therapeutics and biomaterials. This investigation sought to devise a protocol for fabricating customized clinical scale and patient-specific, bioceramic scaffolds for reconstruction of large alveolar bone defects. Two types of calcium phosphate (CaP)-based bioceramic scaffolds (alginate/β-TCP and hydroxyapatite/α-TCP, hereafter referred to as hybrid CaP and Osteoink™, respectively) were designed, 3D printed, and their biocompatibility with alveolar bone marrow stem cells and mechanical properties were determined. Following scaffold optimization, a workflow was developed to use cone beam computed tomographic (CBCT) imaging to design and 3D print, defect-specific bioceramic scaffolds for clinical-scale bone defects. Osteoink™ scaffolds had the highest compressive strength when compared to hybrid CaP with different infill orientation. In cell culture medium, hybrid CaP degradation resulted in decreased pH (6.3) and toxicity to stem cells; however, OsteoInk™ scaffolds maintained a stable pH (7.2) in culture and passed the ISO standard for cytotoxicity. Finally, a clinically feasible laboratory workflow was developed and evaluated using CBCT imaging to engineer customized and defect-specific CaP scaffolds using OsteoInk™. It was determined that printed scaffolds had a high degree of accuracy to fit the respective clinical defects for which they were designed (0.27 mm morphological deviation of printed scaffolds from digital design). From patient to patient, large alveolar bone defects are difficult to treat due to high variability in their complex morphologies and architecture. Our findings shows that Osteoink™ is a biocompatible material for 3D printing of clinically acceptable, patient-specific scaffolds with precision-fit for use in alveolar bone reconstructive procedures. Collectively, emerging digital technologies including CBCT imaging, 3D surgical planning, and (bio)printing can be integrated to address this unmet clinical challenge. [ABSTRACT FROM AUTHOR]

This study examined how range concentrations of Fibroblast Growth Factor-2 (FGF-2) influence the differentiation and activity of human-derived periodontal ligament (hPDLSCs) and alveolar bone-derived stem cells (haBMSCs). hPDLSCs and haBMSCs were cultured with varying concentrations of FGF-2 (0, 1, 2.5, 5, 10, 20 ng/mL) and monitored for osteogenic differentiation through alkaline phosphatase (ALP) activity and quantification of gene expression (qRT-PCR) for osteogenesis markers. Additionally, alizarin red staining and a hydroxyproline colorimetric assay evaluated and quantified osteogenic matrix mineralization and collagen deposition. Statistical analyses were performed using one-way ANOVA or two-way ANOVA for multiple comparisons between groups. At low FGF-2 concentrations, hPDLSCs differentiated toward an osteogenic lineage, whereas higher concentrations of FGF-2 inhibited osteogenesis and promoted fibroblastic differentiation. The effect of FGF-2 at the lowest concentration tested (1 ng/mL) led to significantly higher ALP activity than osteogenically induced positive controls at early time points and equivalent RUNX2 expression at early and later time points. FGF-2 supplementation of haBMSC cultures was sufficient, at all concentrations, to increase ALP activity at an earlier time point. Mineralization of haBMSC cultures increased significantly within 5–20 ng/mL FGF-2 concentrations under basal growth media conditions (α-minimal essential medium supplemented with 15 % fetal bovine serum and 1 % penicillin/streptomycin). FGF-2 has a dual capacity in promoting osteogenic and fibroblastic differentiation within hPDLSCs contingent upon the dosage and timing of administration, alongside supporting osteogenic differentiation in haBMSCs. These findings underscore the need for precision growth factors dosing when considering the design of biomaterials for periodontal regeneration. • Low levels of FGF-2 boost early-stage osteogenic response in PDLSCs. • High levels of FGF-2 impede the osteogenic response in PDLSCs. • FGF-2 enhances mineralization capacity in cultured aBMSCs. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the effects of nanohydroxyapatite (nHAp) particles on the morphological, chemical, physical, and biological properties of chitosan electrospun nanofibers. Materials and methods: nHAp particles with a 1.67 Ca/P ratio were synthesized via the aqueous precipitation method, incorporated into chitosan polymer solution (0.5 wt%), and electrospun into nHAp-loaded fibers (ChHa fibers). Neat chitosan fibers (nHAp-free, Ch fibers) were used as the control. The electrospun fiber mats were characterized using morphological, topographical, chemical, thermal, and a range of biological (antibacterial, antibiofilm, cell viability, and alkaline phosphatase [ALP] activity) analyses. Data were analyzed using ANOVA and Tukey's test (α = 0.05). Results: ChHa fibers demonstrated a bead-like morphology, with thinner (331 ± 110 nm) and smoother (Ra = 2.9 ± 0.3 μm) distribution as compared to the control fibers. Despite showing similar cell viability and ALP activity to Ch fibers, the ChHa fibers demonstrated greater antibacterial potential against most tested bacteria (except for P. intermedia), and higher antibiofilm activity against P. gingivalis biofilm. Conclusions: The incorporation of nHAp particles did not jeopardize the overall morphology, topography, physical, and biological characteristics of the chitosan nanofibers. Clinical relevance: The combination of nHAp particles with chitosan can be used to engineer bioactive, electrospun composite nanofibers with potential applications in regenerative dentistry. [ABSTRACT FROM AUTHOR]

In this work, our original glycol thermal method was applied to obtain borate bioactive glasses of the 45B5 composition (46.1 B 2 O 3 – 26.9 CaO – 24.4 NaO – 2.6 P 2 O 5 , mol%) doped with therapeutic ions Co2+, Cu2+, and Zn2+ aiming toward wound healing applications. The structural analysis performed demonstrated the successful vitreous network obtention, while the apatite mineralization assay exhibited fast conversion into hydroxyapatite (HA, Ca 5 (PO 4) 3 (OH)). Cell viability findings performed with human keratinocytes revealed an absence of cytotoxicity at concentrations below 0.5 mg/mL at day 1, manifested after 3- and 7-days, demonstrating a time- and dose-dependence in vitro outcome. The inhibition halo assay confirmed the antibacterial activity of all glasses against S. aureus. Considering the set of properties evaluated (i.e. , bioactivity, cytocompatibility, and antibacterial activity), the synthesized glasses demonstrate potential for wound healing applications when incorporated into nanofibers, hydrogels, and dermal patches. [ABSTRACT FROM AUTHOR]

• The composite filaments were successfully developed via melt-blending technique. • AMP-PEEK filaments can serve as feedstock for 3D printing of patient-specific implants. • The bioactivity of the composites significantly increased cell adhesion and proliferation. • AMP-PEEK facilitate in vivo osseointegration and suitable bone regeneration capabilities. The aim of this study was to develop bioactive and osseointegrable polyetheretherketone (PEEK)-based composite filaments melt-blended with novel amorphous magnesium phosphate (AMP) particles for 3D printing of dental and orthopedic implants. A series of materials and biological analyses of AMP-PEEK were performed. Thermal stability, thermogravimetric and differential scanning calorimetry curves of as-synthesized AMP were measured. Complex viscosity, elastic modulus and viscous modulus were determined using a rotational rheometer. In vitro bioactivity was analyzed using SBF immersion method. SEM, EDS and XRD were used to study the apatite-forming ability of the AMP-PEEK filaments. Mouse pre-osteoblasts (MC3T3-E1) were cultured and analyzed for cell viability, proliferation and gene expression. For in vivo analyses, bare PEEK was used as the control and 15AMP-PEEK was chosen based on its in vitro cell-related results. After 4 or 12 weeks, animals were euthanized, and the femurs were collected for micro-computed tomography (μ-CT) and histology. The collected findings confirmed the homogeneous dispersion of AMP particles within the PEEK matrix with no phase degradation. Rheological studies demonstrated that AMP-PEEK composites are good candidates for 3D printing by exhibiting high zero-shear and low infinite-shear viscosities. In vitro results revealed enhanced bioactivity and superior pre-osteoblast cell function in the case of AMP-PEEK composites as compared to bare PEEK. In vivo analyses further corroborated the enhanced osseointegration capacity for AMP-PEEK implants. Collectively, the present investigation demonstrated that AMP-PEEK composite filaments can serve as feedstock for 3D printing of orthopedic and dental implants due to enhanced bioactivity and osseointegration capacity. [ABSTRACT FROM AUTHOR]

• Degree of conversion was greater for the CHX-free nanotube-modified adhesive. • Nanotube-modified primers were less viscous than the adhesives. • At 24 h, all groups showed similar bonding performance and structural reliability. • At 6-months, CHX-modified primers resulted in greater bond strength than the control. The purpose of this study was to synthesize chlorhexidine (CHX)-encapsulated aluminosilicate clay nanotubes (Halloysite®, HNTs) and to incorporate them into the primer/adhesive components of an etch-and-rinse adhesive system (SBMP; Scotchbond Multipurpose, 3M ESPE) and to test their effects on degree of conversion, viscosity, immediate and long-term bonding to dentin. CHX-modified HNTs were synthesized using 10% or 20% CHX solutions. The primer and the adhesive components of SBMP were incorporated with 15 wt.% of the CHX-encapsulated HNTs. Degree of conversion (DC) and viscosity analyses were performed to characterize the modified primers/adhesives. For bond strength testing, acid-etched dentin was treated with one of the following: SBMP (control); 0.2%CHX solution before SBMP; CHX-modified primers + SBMP adhesive; SBMP primer + CHX-modified adhesives; and SBMP primer + CHX-free HNT-modified adhesive. The microtensile bond strength test was performed after immediate (24 h) and long-term (6 months) of water storage. Data were analyzed using ANOVA and Tukey (α = 5%) and the Weibull analysis. DC was greater for the CHX-free HNT-modified adhesive, whereas the other experimental adhesives showed similar DC as compared with the control. Primers were less viscous than the adhesives, without significant differences within the respective materials. At 24 h, all groups showed similar bonding performance and structural reliability; whereas at the 6-month period, groups treated with the 0.2%CHX solution prior bonding or with the CHX-modified primers resulted in greater bond strength than the control and superior reliability. The modification of a primer or adhesive with CHX-encapsulated HNTs was an advantageous approach that did not impair the polymerization, viscosity and bonding performance of the materials, showing a promising long-term effect on resin-dentin bonds. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the effect of toothbrush stiffness and dentifrice slurry abrasivity on the development and progression of simulated non-carious cervical lesions (NCCLs). Materials and methods: Human maxillary premolars were allocated to 12 groups generated by the association between toothbrushes, soft, medium, and hard stiffness, and simulated dentifrice slurries, lower, medium, and higher; deionized water (DI) served as negative control. Teeth were mounted on acrylic blocks, and their root surfaces partially covered with acrylic resin to simulate gingiva, leaving a 2-mm area apical to the cemento-enamel junction exposed to toothbrushing. Specimens were brushed with the test slurries for 35,000 and 65,000 double strokes. Impressions taken at baseline and after both brushing periods were scanned by a 3D optical profilometer. Dentin volume loss (mm3) was calculated by image subtraction. Data were analyzed using three-way ANOVA and Fisher's PLSD tests. Results: All toothbrushes caused higher volume loss when associated to higher abrasive slurry, compared to medium- and lower-abrasive slurries. Medium caused more volume loss than lower-abrasive slurry, which led to more volume loss than DI. Hard and medium toothbrushes were not different when used with medium- or higher-abrasive slurries. There were no differences among toothbrushes when used with DI and lower-abrasive slurry. Overall, 35,000 brushing strokes resulted in significantly less volume loss than 65,000. Conclusions: Toothbrush stiffness was an important factor on NCCL development, especially when brushing with medium- and higher-abrasive slurries. Clinical relevance: Medium and hard toothbrushes associated with medium- and high-abrasive toothpastes can yield more severe NCCLs. [ABSTRACT FROM AUTHOR]

This study evaluated the effect of distinct bonding strategies on the retention of full-contour zirconia ceramic (Y-TZP, FCZ) crowns, and it characterized some physicochemical and mechanical properties of FCZ ceramic and its corresponding glazing system. To evaluate retention strength, dies were made with a dentin-analogue material to simulate a prepared tooth. FCZ crowns were manufactured using CAD-CAM technology and allocated into groups according to the bonding strategy: no ceramic treatment (PF – Panavia F cementation), glaze (GL), tribochemical silica coating (CJ), CJ + GL, and piranha solution followed by glaze (PS + GL). The specimens were subjected to thermocycling and storage in distilled water for 100 days before the retention tests. FCZ presented a porosity volume fraction of 0.2%, an apparent density of 6.06 g/cm 3 , Vickers hardness of 12.4 ± 0.07 GPa, and fracture toughness of 5.54 ± 0.24 MPa m 1/2 . SEM revealed a homogeneous microstructure composed of submicron-sized grains. XRD identified mainly zirconia's tetragonal phase. Glaze powder morphology was observed to be irregular, with a nanometric particle size, and a diffraction pattern characteristic of an amorphous material with several peaks of leucite. The PF and GL groups had higher retention values. The majority of the groups presented pre-test bonding failures, and two catastrophic failures of the FCZ-crown (GL and PF groups) were noted. The use of an MDP-containing resin cement or glaze application might improve retention of the FCZ crowns. [ABSTRACT FROM AUTHOR]

Objectives: This article evaluated the drug loading, release kinetics, and matrix metalloproteinase (MMP) inhibition of doxycycline (DOX) released from DOX-loaded nanotube-modified adhesives. DOX was chosen as the model drug, since it is the only MMP inhibitor approved by the U.S. Food and Drug Administration.Materials and methods: Drug loading into the nanotubes was accomplished using DOX solution at distinct concentrations. Increased concentrations of DOX significantly improved the amount of loaded DOX. The modified adhesives were fabricated by incorporating DOX-loaded nanotubes into the adhesive resin of a commercial product. The degree of conversion (DC), Knoop microhardness, DOX release kinetics, antimicrobial, cytocompatibility, and anti-MMP activity of the modified adhesives were investigated.Results: Incorporation of DOX-loaded nanotubes did not compromise DC, Knoop microhardness, or cell compatibility. Higher concentrations of DOX led to an increase in DOX release in a concentration-dependent manner from the modified adhesives. DOX released from the modified adhesives did not inhibit the growth of caries-related bacteria, but more importantly, it did inhibit MMP-1 activity.Conclusions: The loading of DOX into the nanotube-modified adhesives did not compromise the physicochemical properties of the adhesives and the released levels of DOX were able to inhibit MMP activity without cytotoxicity.Clinical significance: Doxycycline released from the nanotube-modified adhesives inhibited MMP activity in a concentration-dependent fashion. Therefore, the proposed nanotube-modified adhesive may hold clinical potential as a strategy to preserve resin/dentin bond stability. [ABSTRACT FROM AUTHOR]

The aim was to assess the shear bond strength (SBS) of lithium disilicate (LD) ceramic to resin composite with different universal adhesives, duration of ageing and silane. One hundred and twenty LD ceramic discs were processed, fired and etched (HF acid 5%) for 20 s (sec). All specimens were divided into 12 groups (n = 10), based on different combinations of, 3 different universal adhesives [Scotchbond (SB) Universal Adhesive, All-Bond (AB) Universal, and Futurabond U (FU)], silane and different duration of ageing [24 h and 3 months]. Composite resin cylinders (Tetric ceram) (3mm × 2 mm) were formed using bonding jig on ceramic and were light-cured. The specimens in groups 1–6 and 7–12 were stored in distilled water (37 °C) for 24 h and 3 months (thermocycling -5000 cycles 5–55 °C/30 s dwell time) before being subjected to bond strength testing respectively. Using universal testing machine shear bond test was performed at a crosshead speed of 1 mm/min. Failure modes and fracture patterns were assessed using stereomicroscope and scanning electron microscope. Analysis of variance was performed to analyze data. SBS was significantly higher with silane than without silane (p < 0.01), regardless of the type of adhesive or storage duration. Specimens tested at 24 h storage showed significantly higher (p < 0.01) SBS than specimens tested after 3-months. A comparison among different universal adhesives showed significantly distinct bond strength (p < 0.01). Optimal bonds to LD were achieved by application of silane. While ageing through storage had a negative impact on the SBS, it varied among different adhesives. [ABSTRACT FROM PUBLISHER]

This study aimed to evaluate the effect of various zirconia surface pretreatments on the adhesion between full contour 3Y-TZP zirconia and glaze, and the shear bond strength (SBS) between glazed/3Y-TZP and resin cement. Specimens were allocated into groups: GL-glaze; AL+GL-sandblasting with Al 2 O 3 +GL; CJ+GL-tribochemical silica coating (Cojet ® /CJ)+GL; PS+GL-piranha solution+GL; and CJ. Adhesion between 3Y-TZP and GL was evaluated using the scratch test. Surface topography and glaze thickness were evaluated by using a scanning electron microscope (SEM). For SBS, glazed/3Y-TZP surface was etched with hydrofluoric acid and a silane was applied. For CJ only the silane was applied. Samples were tested after 24 h (24 h wet) or after 15,000 thermal cycles and 90 days storage (thermocycled). After SBS, the type of failure was classified as: adhesive, mixed or cohesive. The data were analyzed using two-way ANOVA and Tukey's test. SEM analysis after scratch test revealed circular cracks in the GL group and conformal cracks in the others groups. SEM micrographs suggested that zirconia specimens submitted to airborne-particle abrasion presents rougher and porous surface when compared to surfaces treated with GL and PS. The glaze layer was approximately 1.86 µm thick in all groups. After 24 h, SBS test showed highest values for AL+GL and CJ+GL and were significantly higher when compared to the GL group. Differences were not significant between PS+GL and the other groups. After aging (thermocycling+storage), groups GL and CJ presented no statistically significant difference compared to 24 h and aged AL+GL, CJ+GL and PS+GL groups. The predominant type of failure was mixed. 3Y-TZP surface treatment with glaze application could be considered as an alternative treatment, since it yielded a similar resin bond strength without the need for airborne-particle abrasion. [ABSTRACT FROM AUTHOR]

To evaluate the effect of surface treatments, finishing condition (polished vs. ground) and aging on the microtensile bond strength of a CAD/CAM resin composite to resin cement. CAD/CAM resin composite blocks (Tetric CAD HT) were sectioned (7 × 12 × 4 mm), randomly divided according to finishing condition (polished or ground) and surface treatment groups (Ctrl: no treatment; AA: air-abrasion with 110 μm Al 2 O 3 powder; TBS: tribochemical silica coating). A coupling agent corresponding to each surface treatment was applied for cementation (Ctrl and AA groups: ExciTE F DSC; TBS group: RelyX Ceramic Primer) and each block was adhesively cemented (Variolink N) with another one from the same conditioning. Next, 1 mm2 cross-section beams were produced after sectioning, with half being tested under microtensile test after 24 h, while the other half was aged (25,000 cycles of thermocycling + 90 days of storage) (n = 50). Contact angle and Scanning Electron Microscopy (SEM) analysis were performed. Bond strength data (MPa) were statistically analyzed using Three-way ANOVA and Tukey tests (α = 0.05). The failure types were examined and classified as predominantly adhesive, cohesive or mixed under stereomicroscopy. The surface treatments (AA and TBS) promoted higher bond strength than the Ctrl group. Grinding finishing improved the bond strength only when no treatment was performed (Ctrl group), having a negative effect for the TBS treatment. The long-term aging damaged the resin bond, independent of the condition. The failure analysis showed that 92% of the failures were classified as adhesive in the baseline conditions, and 94.7% in aged specimens. TBS showed the lowest contact angle among the tested groups for both conditions (baseline and aged). Surface conditioning with alumina particle air-abrasion or tribochemical silica coating improves the bond strength. CAD/CAM milling roughness induces better surface condition for adhesion, in particular when no treatment is performed. Bond degradation occurs after long-term aging for all the test conditions. When luting CAD/CAM resin composite restorations, the surface treatment and roughness due to the grinding by burs in the manufacturing process influence the adhesion of restoration to resin cement. • The machining roughness simulation influences the bond strength of the CAD-CAM resin composite to resin cement. • Alumina particle air-abrasion lead to the higher bond strength for a milled composite resin surface. • Treated polished surfaces has higher reduction in bond strength after long-term aging. • Tribochemical surface treatment has the lowest reduction in bond strength after aging. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of Halloysite® aluminosilicate clay nanotubes (HNTs) addition on selected physical, mechanical, and biological properties of experimental adhesive resins.Methods: Experimental dentin adhesive resins were prepared by mixing Bis-GMA, TEGDMA, HEMA (50/25/25wt.%), and photo-initiators. As-received HNTs were then incorporated into the resin mixture at distinct concentrations: 0 (HNT-free, control), 1, 2.5, 5, 7.5, 10, and 20wt.%. The degree of conversion (DC), radiopacity (RP), Knoop hardness (KHN), flexural strength (FS), and cytotoxicity analyses were carried out for each adhesive formulation. The adhesive resin of Adper Scotchbond Multi-Purpose (SBMP) was used as the commercially available reference for both the RP and cytotoxicity tests. Data were statistically analyzed using One-Way ANOVA and Tukey's test (p≤0.05).Results: All adhesives exhibited similar DC (p=0.1931). The RP of adhesives was improved with the addition of up to 5wt.% of HNTs (p<0.001). Adhesives containing 5-10wt.% of HNTs led to greater KHN when compared to the control (p<0.001). The FS was reduced only when 20wt.% of HNTs was added (p≤0.001). None of the prepared adhesives was cytotoxic.Conclusion: The incorporation of up to 10wt.% of HNTs into the adhesive resins did not jeopardize the tested physical and biological properties.Clinical Significance: When using HNTs as carriers of drugs/bioactive compounds, the amount of the former added into adhesive resin materials should not exceed 10wt.%; otherwise, a significant reduction in physicomechanical properties may be expected. [ABSTRACT FROM AUTHOR]

Objectives This study reports on the synthesis, materials characterization, antimicrobial capacity, and cytocompatibility of novel ZnO-loaded membranes for guided tissue/bone regeneration (GTR/GBR). Methods Poly(ɛ-caprolactone) (PCL) and PCL/gelatin (PCL/GEL) were dissolved in hexafluoropropanol and loaded with ZnO at distinct concentrations: 0 (control), 5, 15, and 30 wt.%. Electrospinning was performed using optimized parameters and the fibers were characterized via scanning and transmission electron microscopies (SEM/TEM), energy dispersive X-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), contact angle (CA), mechanical testing, antimicrobial activity against periodontopathogens, and cytotoxicity test using human dental pulp stem cells (hDPSCs). Data were analyzed using ANOVA and Tukey ( α = 5%). Results ZnO nanoparticles were successfully incorporated into the overall submicron fibers, which showed fairly good morphology and microstructure. Upon ZnO nanoparticles’ incorporation, the PCL and PCL/GEL fibers became thicker and thinner, respectively. All GEL-containing membranes showed lower CA than the PCL-based membranes, which were highly hydrophobic. Overall, the mechanical properties of the membranes were reduced upon ZnO incorporation, except for PCL-based membranes containing ZnO at the 30 wt.% concentration. The presence of GEL enhanced the stretching ability of membranes under wet conditions. All ZnO-containing membranes displayed antibacterial activity against the bacteria tested, which was generally more pronounced with increased ZnO content. All membranes synthesized in this study demonstrated satisfactory cytocompatibility, although the presence of 30 wt.% ZnO led to decreased viability. Significance Collectively, this study suggests that PCL- and PCL/GEL-based membranes containing a low content of ZnO nanoparticles can potentially function as a biologically safe antimicrobial GTR/GBR membrane. [ABSTRACT FROM AUTHOR]

We tested the ability of the axolotl (Ambystoma mexicanum) fibula to regenerate across segment defects of different size in the absence of intervention or after implant of a unique 8-braid pig small intestine submucosa (SIS) scaffold, with or without incorporated growth factor combinations or tissue protein extract. Fractures and defects of 10% and 20% of the total limb length regenerated well without any intervention, but 40% and 50% defects failed to regenerate after either simple removal of bone or implanting SIS scaffold alone. By contrast, scaffold soaked in the growth factor combination BMP-4/HGF or in protein extract of intact limb tissue promoted partial or extensive induction of cartilage and bone across 50% segment defects in 30%-33% of cases. These results show that BMP-4/HGF and intact tissue protein extract can promote the events required to induce cartilage and bone formation across a segment defect larger than critical size and that the long bones of axolotl limbs are an inexpensive model to screen soluble factors and natural and synthetic scaffolds for their efficacy in stimulating this process. [ABSTRACT FROM AUTHOR]

Objectives: As an initial step toward our goal of developing a completely tissue-engineered larynx, the aim of this study was to describe and compare three strategies of creating tissue-engineered muscle-polymer constructs for hemilaryngeal reconstruction. Methods: Cartilage-mimicking polymer was developed from electrospun poly(D,L-lactide-co-s-caprolactone) (PCL). Primary muscle progenitor cell cultures were derived from syngeneic F344 rat skeletal muscle biopsies. Twenty F344 rats underwent resection of the outer hemilaryngeal cartilage with the underlying laryngeal adductor muscle. The defects were repaired with muscle stem cell-derived muscle-PCL constructs (5 animals), myotube-derived muscle-PCL constructs (5 animals), motor end plate-expressing muscle-PCL constructs (5 animals), or PCL alone (controls; 5 animals). The outcome measures at 1 month included animal survival, muscle thickness, and innervation status as determined by electromyography and immunohistochemistry. Results: All of the animals survived the 1-month implant period and had appropriate weight gain. The group that received motor end plate-expressing muscle-PCL constructs demonstrated the greatest muscle thickness and the strongest innervation, according to electromyographic activity and the percentage of motor end plates that had nerve contact. Conclusions: Although all of the tissue-engineered constructs provided effective reconstruction, those that expressed motor end plates before implantation yielded muscle that was more strongly innervated and viable. This finding suggests that this novel approach may be useful in the development of a tissue-engineered laryngeal replacement. [ABSTRACT FROM AUTHOR]

This study aimed at engineering cytocompatible and injectable antibiotic-laden fibrous microparticles gelatin methacryloyl (GelMA) hydrogels for endodontic infection ablation. Clindamycin (CLIN) or metronidazole (MET) was added to a polymer solution and electrospun into fibrous mats, which were processed via cryomilling to obtain CLIN- or MET-laden fibrous microparticles. Then, GelMA was modified with CLIN- or MET-laden microparticles or by using equal amounts of each set of fibrous microparticles. Morphological characterization of electrospun fibers and cryomilled particles was performed via scanning electron microscopy (SEM). The experimental hydrogels were further examined for swelling, degradation, and toxicity to dental stem cells, as well as antimicrobial action against endodontic pathogens (agar diffusion) and biofilm inhibition, evaluated both quantitatively (CFU/mL) and qualitatively via confocal laser scanning microscopy (CLSM) and SEM. Data were analyzed using ANOVA and Tukey's test (α = 0.05). The modification of GelMA with antibiotic-laden fibrous microparticles increased the hydrogel swelling ratio and degradation rate. Cell viability was slightly reduced, although without any significant toxicity (cell viability > 50%). All hydrogels containing antibiotic-laden fibrous microparticles displayed antibiofilm effects, with the dentin substrate showing nearly complete elimination of viable bacteria. Altogether, our findings suggest that the engineered injectable antibiotic-laden fibrous microparticles hydrogels hold clinical prospects for endodontic infection ablation. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of polishing techniques on the surface roughness of Y-TZP ceramic and on the wear behavior of synthetic hydroxyapatite (HA). Methods: Thirty-two full-contour Y-TZP (Diazir®) sliders (φ =2mm×1.5mm in height) were manufactured using CAD/CAM, embedded in acrylic resin using brass holders, and randomly allocated into four groups (n =8): according to the finishing/polishing procedure: G1-as-machined, G2-glazed, G3-diamond bur finishing and G4−G3+OptraFine® polishing kit. Thirty-two sintered HA disks (φ =13mm×2.9mm in height) were similarly mounted in brass holders. Y-TZP sliders baseline surface roughness values (Ra and Rq, in μm) were recorded using a non-contact profilometer (Proscan 2000). A two-body pin-on-disc wear test was performed. HA height (μm) and volume (mm3) losses were measured. Y-TZP height loss was measured using a digital micrometer. One-way ANOVA was used to determine the effect of the polishing techniques on the surface roughness. Comparisons between groups for differences in antagonist height loss/volume, and slider height loss were performed using one-way ANOVA. Statistical significance was set at α =0.05. Results: Roughness measurements showed significant differences (p =0.0001) among the surface treatments with G1 (Ra=0.84, Rq=1.13μm) and G3 (Ra=0.89, Rq=1.2μm) being the roughest, and G2 (Ra=0.42, Rq=0.63μm) the smoothest (p =0.0001). Y-TZP slider height loss was highest for the glazed group (35.39μm), and was lowest for the polished group (6.61μm) (p =0.0001). Antagonist volume and height losses for groups (G1–G3) were similar, while the polished group (1.3mm3, 14.7μm) showed significant lower values (p =0.0001). Significance: Although glazed zirconia provides an initially smooth surface, significantly increased antagonist wear was observed compared to the polished Y-TZP zirconia surface. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this review is to highlight recent progress in the field of biomaterials-mediated dental pulp tissue engineering. Specifically, we aim to underscore the critical design criteria of biomaterial platforms that are advantageous for pulp tissue engineering, discuss models for preclinical evaluation, and present new and innovative multifunctional strategies that hold promise for clinical translation.The current article is a comprehensive overview of recent progress over the last 5 years. In detail, we surveyed the literature in regenerative pulp biology, including novel biologic and biomaterials approaches, and those that combined multiple strategies, towards more clinically relevant models. PubMed searches were performed using the keywords: “regenerative dentistry,” “dental pulp regeneration,” “regenerative endodontics,” and “dental pulp therapy.”Significant contributions to the field of regenerative dentistry have been made in the last 5 years, as evidenced by a significant body of publications. We chose exemplary studies that we believe are progressive towards clinically translatable solutions. We close this review with an outlook towards the future of pulp regeneration strategies and their clinical translation.Current clinical treatments lack functional and predictable pulp regeneration and are more focused on the treatment of the consequences of pulp exposure, rather than the restoration of healthy dental pulp.Clinically, there is great demand for bioinspired biomaterial strategies that are safe, efficacious, and easy to use, and clinicians are eager for their clinical translation. In particular, we place emphasis on strategies that combine favorable angiogenesis, mineralization, and functional tissue formation, while limiting immune reaction, risk of microbial infection, and pulp necrosis.Materials and methods: The aim of this review is to highlight recent progress in the field of biomaterials-mediated dental pulp tissue engineering. Specifically, we aim to underscore the critical design criteria of biomaterial platforms that are advantageous for pulp tissue engineering, discuss models for preclinical evaluation, and present new and innovative multifunctional strategies that hold promise for clinical translation.The current article is a comprehensive overview of recent progress over the last 5 years. In detail, we surveyed the literature in regenerative pulp biology, including novel biologic and biomaterials approaches, and those that combined multiple strategies, towards more clinically relevant models. PubMed searches were performed using the keywords: “regenerative dentistry,” “dental pulp regeneration,” “regenerative endodontics,” and “dental pulp therapy.”Significant contributions to the field of regenerative dentistry have been made in the last 5 years, as evidenced by a significant body of publications. We chose exemplary studies that we believe are progressive towards clinically translatable solutions. We close this review with an outlook towards the future of pulp regeneration strategies and their clinical translation.Current clinical treatments lack functional and predictable pulp regeneration and are more focused on the treatment of the consequences of pulp exposure, rather than the restoration of healthy dental pulp.Clinically, there is great demand for bioinspired biomaterial strategies that are safe, efficacious, and easy to use, and clinicians are eager for their clinical translation. In particular, we place emphasis on strategies that combine favorable angiogenesis, mineralization, and functional tissue formation, while limiting immune reaction, risk of microbial infection, and pulp necrosis.Results: The aim of this review is to highlight recent progress in the field of biomaterials-mediated dental pulp tissue engineering. Specifically, we aim to underscore the critical design criteria of biomaterial platforms that are advantageous for pulp tissue engineering, discuss models for preclinical evaluation, and present new and innovative multifunctional strategies that hold promise for clinical translation.The current article is a comprehensive overview of recent progress over the last 5 years. In detail, we surveyed the literature in regenerative pulp biology, including novel biologic and biomaterials approaches, and those that combined multiple strategies, towards more clinically relevant models. PubMed searches were performed using the keywords: “regenerative dentistry,” “dental pulp regeneration,” “regenerative endodontics,” and “dental pulp therapy.”Significant contributions to the field of regenerative dentistry have been made in the last 5 years, as evidenced by a significant body of publications. We chose exemplary studies that we believe are progressive towards clinically translatable solutions. We close this review with an outlook towards the future of pulp regeneration strategies and their clinical translation.Current clinical treatments lack functional and predictable pulp regeneration and are more focused on the treatment of the consequences of pulp exposure, rather than the restoration of healthy dental pulp.Clinically, there is great demand for bioinspired biomaterial strategies that are safe, efficacious, and easy to use, and clinicians are eager for their clinical translation. In particular, we place emphasis on strategies that combine favorable angiogenesis, mineralization, and functional tissue formation, while limiting immune reaction, risk of microbial infection, and pulp necrosis.Conclusions: The aim of this review is to highlight recent progress in the field of biomaterials-mediated dental pulp tissue engineering. Specifically, we aim to underscore the critical design criteria of biomaterial platforms that are advantageous for pulp tissue engineering, discuss models for preclinical evaluation, and present new and innovative multifunctional strategies that hold promise for clinical translation.The current article is a comprehensive overview of recent progress over the last 5 years. In detail, we surveyed the literature in regenerative pulp biology, including novel biologic and biomaterials approaches, and those that combined multiple strategies, towards more clinically relevant models. PubMed searches were performed using the keywords: “regenerative dentistry,” “dental pulp regeneration,” “regenerative endodontics,” and “dental pulp therapy.”Significant contributions to the field of regenerative dentistry have been made in the last 5 years, as evidenced by a significant body of publications. We chose exemplary studies that we believe are progressive towards clinically translatable solutions. We close this review with an outlook towards the future of pulp regeneration strategies and their clinical translation.Current clinical treatments lack functional and predictable pulp regeneration and are more focused on the treatment of the consequences of pulp exposure, rather than the restoration of healthy dental pulp.Clinically, there is great demand for bioinspired biomaterial strategies that are safe, efficacious, and easy to use, and clinicians are eager for their clinical translation. In particular, we place emphasis on strategies that combine favorable angiogenesis, mineralization, and functional tissue formation, while limiting immune reaction, risk of microbial infection, and pulp necrosis.Clinical relevance: The aim of this review is to highlight recent progress in the field of biomaterials-mediated dental pulp tissue engineering. Specifically, we aim to underscore the critical design criteria of biomaterial platforms that are advantageous for pulp tissue engineering, discuss models for preclinical evaluation, and present new and innovative multifunctional strategies that hold promise for clinical translation.The current article is a comprehensive overview of recent progress over the last 5 years. In detail, we surveyed the literature in regenerative pulp biology, including novel biologic and biomaterials approaches, and those that combined multiple strategies, towards more clinically relevant models. PubMed searches were performed using the keywords: “regenerative dentistry,” “dental pulp regeneration,” “regenerative endodontics,” and “dental pulp therapy.”Significant contributions to the field of regenerative dentistry have been made in the last 5 years, as evidenced by a significant body of publications. We chose exemplary studies that we believe are progressive towards clinically translatable solutions. We close this review with an outlook towards the future of pulp regeneration strategies and their clinical translation.Current clinical treatments lack functional and predictable pulp regeneration and are more focused on the treatment of the consequences of pulp exposure, rather than the restoration of healthy dental pulp.Clinically, there is great demand for bioinspired biomaterial strategies that are safe, efficacious, and easy to use, and clinicians are eager for their clinical translation. In particular, we place emphasis on strategies that combine favorable angiogenesis, mineralization, and functional tissue formation, while limiting immune reaction, risk of microbial infection, and pulp necrosis. [ABSTRACT FROM AUTHOR]

• A drug delivery system to afford sustained release of DEX was achieved by CD-IC. • DEX/CD-IC was successfully incorporated into PLGA fibers via electrospinning. • UPLC revealed the solubility enhancement and sustained release of DEX by CD-IC. • Cell compatibility and proliferation was more favorable in DEX/CD-IC fibers. • Odonto/osteogenic differentiation was enhanced in DEX/CD-IC electrospun fibers. Beta-cyclodextrin (β-CD) is an oligosaccharide commonly used to improve the aqueous solubility of lipophilic drugs (e.g., dexamethasone, DEX). Here we present the development of a drug delivery system to provide sustained release of DEX by β-CD-inclusion complex (IC) to amplify the mineralization capacity of stem cells from human-extracted deciduous teeth (SHEDs) as a potential direct pulp capping strategy. First, IC of DEX (DEX-CD-IC) was synthesized with β-CD. To confirm DEX-CD-IC complex formation, X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analyses were performed. XRD data indicated that IC formation was achieved due to formation of a new crystalline structure, whereas FTIR revealed the presence of the IC from the shifting of the peaks of each component in DEX-CD-IC. Then, electrospun poly(lactic-co-glycolic acid, PLGA) fibers (PLGA/DEX-CD-IC) were processed by varying the concentration of DEX-CD-IC (5%, 10 %, and 15 %). The release of DEX from fibers was determined by ultraperformance liquid chromatography for 28 days. Thanks to the solubility enhancement of DEX by IC, electrospun PLGA/DEX-CD-IC fibers released DEX in a more sustained fashion compared to PLGA/DEX fibers. No deleterious effect was found in terms of SHEDs' proliferation when cultured with or on electrospun fibers, regardless of the IC presence. Importantly, a more pronounced odontogenic differentiation was stimulated by electrospun fibers loaded with the lowest DEX-CD-IC concentration (5%), as a result of the sustained DEX release. In sum, PLGA/DEX-CD-IC fibers have great potential in vital dental pulp therapy, owing to its sustained DEX release, cytocompatibility, and odontogenic differentiation capacity. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To evaluate the null hypotheses that hydrofluoric (HF) acid etching time would neither decrease the biaxial flexural strength of a glass-based veneering ceramic nor enhance it after silane and unfilled resin (UR) applications. Methods: Disc-shaped IPS e.max ZirPress specimens were allocated into 12 groups: G1-control (no-etching), G2-30s, G3-60s, G4-90s, G5-120s, G6-60s+60s. Groups (G7–G12) were treated in the same fashion as G1–G6, but followed by silane and UR applications. Surface morphology and roughness (Ra and Rq) of the ceramics were assessed by means of scanning electron microscopy (SEM) and profilometry, respectively. Flexural strength was determined by biaxial testing. Data were analyzed by two-way ANOVA and the Sidak test (α =0.05). Weibull statistics were estimated and finite element analysis (FEA) was carried out to verify the stress concentration end areas of fracture. Results: The interaction (etching time vs. surface treatment) was significant for Ra (p =0.008) and Rq (0.0075). Resin-treated groups presented significantly lower Ra and Rq than non-treated groups, except for the 60s group (p <0.005). SEM revealed that etching affected the ceramic microstructure and that the UR was able to penetrate into the irregularities. A significant effect of etching time (p =0.029) on flexural strength was seen. G7–G12 presented higher strength than G1–G6 (p <0.0001). None of experimental groups failed to show 95% confidence intervals of σ 0 and m overlapped. FEA showed lower stress concentration after resin treatment. Significance: HF acid etching time did not show a damaging effect on the ceramic flexural strength. Moreover, the flexural strength could be enhanced after UR treatment. [Copyright &y& Elsevier]