Editor’s Choice Articles

The early diagnosis of certain fatal diseases is vital for preventing severe consequences and contributes to a more effective treatment. Despite numerous conventional methods to realize this goal, employing nanobiosensors is a novel approach that provides a fast and precise detection. Recently, nanomaterials have been widely applied as biosensors with distinctive features. Graphite phase carbon nitride (g-C₃N₄) is a two-dimensional (2D) carbon-based nanostructure that has received attention in biosensing. Biocompatibility, biodegradability, semiconductivity, high photoluminescence yield, low-cost synthesis, easy production process, antimicrobial activity, and high stability are prominent properties that have rendered g-C₃N₄ a promising candidate to be used in electrochemical, optical, and other kinds of biosensors. This review presents the g-C₃N₄ unique features, synthesis methods, and g-C₃N₄-based nanomaterials. In addition, recent relevant studies on using g-C₃N₄ in biosensors in regard to improving treatment pathways are reviewed. Full article

The microstructural and molecular-scale variations induced by laser irradiation treatment on human teeth enamel in comparison with synthetic hydroxyapatite (HAp) were examined through Raman microprobe spectroscopy as a function of irradiation power. The results demonstrated that laser irradiation could modify stoichiometry, microstructure, and the population of crystallographic defects, as well as the hardness of the materials. These modifications showed strong dependences on both laser power and initial nonstoichiometric structure (defective content of HPO₄), because of the occurrence of distinct reactions and structural reconstruction. The reported observations can redirect future trends in tooth whitening by laser treatment and the production of HAp coatings because of the important role of stoichiometric defects. Full article

Background: We had previously synthetized a macromolecular prodrug consisting of oxidized Alginate and dopamine (AlgOx-Da) for a potential application in Parkinson disease (PD). Methods: In the present work, we aimed at gaining an insight into the interactions occurring between AlgOx-Da and SH-SY5Y neuronal cell lines in view of further studies oriented towards PD treatment. With the scope of ascertaining changes in the external and internal structure of the cells, multiple methodologies were adopted. Firstly, fluorescently labeled AlgOx-Da conjugate was synthetized in the presence of fluorescein 5(6)-isothiocyanate (FITC), providing FITC-AlgOx-Da, which did not alter SH-SY5Y cell viability according to the sulforhodamine B test. Furthermore, the uptake of FITC-AlgOx-Da by the SH-SY5Y cells was studied using scanning near-field optical microscopy and assessments of cell morphology over time were carried out using atomic force microscopy. Results: Notably, the AFM methodology confirmed that no relevant damage occurred to the neuronal cells. Regarding the effects of DA on the intracellular reactive oxygen species (ROS) production, AlgOx-Da reduced them in comparison to free DA, while AlgOx did almost not influence ROS production. Conclusions: these findings seem promising for designing in vivo studies aiming at administering Oxidized Alginate Dopamine Conjugate for PD treatment. Full article

The study evaluated the interaction of a titanium dental implant surface with three different antibacterial solutions: chlorhexidine, povidone-iodine, and chlorine dioxide. Implant surface decontamination is greatly challenging modern implant dentistry. Alongside mechanical cleaning, different antibacterial agents are widely used, though these could alter implant surface properties. Commercially pure (CP) grade 4 titanium (Ti) discs were treated with three different chemical agents (chlorhexidine 0.2% (CHX), povidone-iodine 10% (PVPI), chlorine dioxide 0.12% (ClO₂)) for 5 min. Contact angle measurements, X-ray photoelectron spectroscopy (XPS) analysis, and cell culture studies were performed. Attachment and proliferation of primary human osteoblast cells were investigated via MTT (dimethylthiazol–diphenyl tetrazolium bromide), alamarBlue, LDH (lactate dehydrogenase), and fluorescent assays. Contact angle measurements showed that PVPI-treated samples (Θ = 24.9 ± 4.1) gave no difference compared with controls (Θ = 24.6 ± 5.4), while CHX (Θ = 47.2 ± 4.1) and ClO₂ (Θ = 39.2 ± 9.8) treatments presented significantly higher Θ values. All samples remained in the hydrophilic region. XPS analysis revealed typical surface elements of CP grade 4 titanium (Ti, O, and C). Both MTT and alamarBlue cell viability assays showed similarity between treated and untreated control groups. The LDH test revealed no significant difference, and fluorescent staining confirmed these results. Although there was a difference in surface wettability, a high proliferation rate was observed in all treated groups. The in vitro study proved that CHX, PVPI, and ClO₂ are proper candidates as dental implant decontamination agents. Full article

The intersection of the bone tissue reconstruction and additive manufacturing fields promoted the advancement to a prerequisite and new feedstock resource for high-performance bone-like-scaffolds manufacturing. In this paper, the proposed strategy was directed toward the use of bovine-bone-derived hydroxyapatite (HA) for surface properties enhancement and mechanical features reinforcement of the poly(lactic acid) matrix for composite filaments extrusion. The involvement of completely naturally derived materials in the technological process was based on factors such as sustainability, low cost, and a facile and green synthesis route. After the HA isolation and extraction from bovine bones by thermal processing, milling, and sorting, two dependent parameters—the HA particles size (<40 μm, <100 μm, and >125 μm) and ratio (0–50% with increments of 10%)—were simultaneously modulated for the first time during the incorporation into the polymeric matrix. The resulting melt mixtures were divided for cast pellets and extruded filaments development. Based on the obtained samples, the study was further designed to examine several key features by complementary surface–volume characterization techniques. Hence, the scanning electron microscopy and micro-CT results for all specimens revealed a uniform and homogenous dispersion of HA particles and an adequate adhesion at the ceramic/polymer interface, without outline pores, sustained by the shape and surface features of the synthesized ceramic particles. Moreover, an enhanced wettability (contact angle in the ~70−21° range) and gradual mechanical takeover were indicated once the HA ratio increased, independent of the particles size, which confirmed the benefits and feasibility of evenly blending the natural ceramic/polymeric components. The results correlation led to the selection of optimal technological parameters for the synthesis of adequate composite filaments destined for future additive manufacturing and biomedical applications. Full article

Chitosan and composite fibers containing chitin nanofibrils have been developed for use in cosmetology. The tensile strength of the chitosan multifilaments is 160.6 ± 19.0 MPa, and of the composite multifilaments containing chitin, nanofibrils are 198.0 ± 18.4 MPa. Chitin nanofibrils introduced into the chitosan solution contribute to the creation of a new spatial arrangement of chitosan chains and their denser packing. The studies carried out by optical, scanning electron, and atomic force microscopy has shown that the serum, consisting of a mixture of lactic acid and sodium lactate, contains extended oriented structures—“liquid filaments”. It has been also shown that a mixture of serum and composite fibers based on chitosan and chitin nanofibrils has mucoadhesive, film-forming properties. The introduction of composite fibers containing chitin nanofibrils into the serum promotes the reinforcing effect of liquid filaments, the lifting effect of the film. The obtained composition can be used in cosmetology as a skin care product. Full article

Background: Sequential chemical application for irrigating a root canal during chemomechanical debridement can affect the dentin microstructure. Understanding the effects of various irrigants on chemical properties of dentin can elucidate their effects on physical properties and thereby explain the higher incidence of structural failure in endodontically treated teeth. This in vitro research aimed to compare and evaluate the effects of three different irrigating solutions on the chemical structure of root canal dentin in extracted human teeth. Methods: Forty-eight extracted single-rooted mandibular premolar teeth were sectioned at the cemento–enamel junction by a diamond disc and were then randomly assigned to four groups of twelve samples each. The groups were irrigated using 5.25% NaOCl, ozonated olive oil, silver citrate, or distilled water. Dentin sections measuring 1.5 mm were obtained from the root portion and each section and were analyzed using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and electron-dispersive spectroscopy (EDS). FTIR and EDS values are reported as means ± standard deviations. Data were analyzed using an ANOVA and a post hoc Bonferroni test (p < 0.05). Results: A comparison of the FTIR and EDS values among the groups using ANOVA revealed statistically significant differences in the organic and inorganic peak values among the groups. An intergroup comparison between NaOCl with silver citrate and ozonated olive oil revealed significant reductions in the carbonate and phosphate peak values in the NaOCl group (p < 0.05). The EDS values tabulated for the carbon, oxygen, phosphorous, and calcium peak levels showed significant differences between the groups using an ANOVA. An SEM analysis was conducted under 1500× magnification, which revealed smear layer removal in the silver citrate group. Conclusions: The silver citrate solution and the ozonated olive oil caused less changes in the organic and mineral contents of dentin than sodium hypochlorite. Full article

The advent of nanotechnology has brought about revolutionary innovations in biological research techniques and medical practice. In recent years, various “smart” nanocarriers have been introduced to deliver therapeutic agents specifically to the tumor tissue in a controlled manner, thereby minimizing their side effects and reducing both dosage and dosage frequency. A large number of nanoparticles have demonstrated initial success in preclinical evaluation but modest therapeutic benefits in the clinical setting, partly due to insufficient delivery to the tumor site and penetration in tumor tissue. Therefore, a precise understanding of the relationships betweenthe physicochemical properties of nanoparticles and their interaction with the surrounding microenvironment in the body is extremely important for achieving higher concentrations and better functionality in tumor tissues. This knowledge would help to effectively combine multiple advantageous functions in one nanoparticle. The main focus of the discussion in this review, therefore, will relate to the main physicochemical properties of nanoparticles while interacting within the body and their tuning potential for increased performance. Full article

Bacteria-associated late infection of the orthopedic devices would further lead to the failure of the implantation. However, present ordinary antimicrobial strategies usually deal with early infection but fail to combat the late infection of the implants due to the burst release of the antibiotics. Thus, to fabricate long-term antimicrobial (early antibacterial, late antibacterial) orthopedic implants is essential to address this issue. Herein, we developed a sophisticated MAO-I₂-PCLx coating system incorporating an underlying iodine layer and an upper layer of polycaprolactone (PCL)-controlled coating, which could effectively eradicate the late bacterial infection throughout the implantation. Firstly, micro-arc oxidation was used to form a microarray tubular structure on the surface of the implants, laying the foundation for iodine loading and PCL bonding. Secondly, electrophoresis was applied to load iodine in the tubular structure as an efficient bactericidal agent. Finally, the surface-bonded PCL coating acts as a controller to regulate the release of iodine. The hybrid coatings displayed great stability and control release capacity. Excellent antibacterial ability was validated at 30 days post-implantation via in vitro experiments and in vivo rat osteomyelitis model. Expectedly, it can become a promising bench-to-bedside strategy for current infection challenges in the orthopedic field. Full article

Bone tissue infection is a major clinical challenge with high morbidity and a significant healthcare burden. Therapeutic approaches are usually based on systemic antibacterial therapies, despite the potential adverse effects associated with antibiotic resistance, persistent and opportunistic infections, hypersensitivity, and toxicity issues. Most recently, tissue engineering strategies, embracing local delivery systems and antibacterial biomaterials, have emerged as a promising alternative to systemic treatments. Despite the reported efficacy in managing bacterial infection, little is known regarding the outcomes of these devices on the bone healing process. Accordingly, this systematic review aims, for the first time, to characterize the efficacy of antibacterial biomaterials/tissue engineering constructs on the healing process of the infected bone within experimental animal models and upon microtomographic characterization. Briefly, a systematic evaluation of pre-clinical studies was performed according to the PRISMA guidelines, further complemented with bias analysis and methodological quality assessments. Data reported a significant improvement in the healing of the infected bone when an antibacterial construct was implanted, compared with the control—construct devoid of antibacterial activity, particularly at longer time points. Furthermore, considering the assessment of bias, most included studies revealed an inadequate reporting methodology, which may lead to an unclear or high risk of bias and directly hinder future studies. Full article

Current dental adhesives lack antibacterial properties. This study aimed to explore the effect of incorporating benzyldimethyldodecyl ammonium chloride (BDMDAC) on the degree of conversion, contact angle, ultimate tensile strength (UTS), microtensile bond strength (µTBS), cytotoxicity, antibacterial and bonding performance after artificial aging. A dental adhesive was doped with BDMDAC in the concentration range of 1–5 wt.%. For antibacterial assays, the BDMDAC compound was subject to planktonic cells of Streptococcus mutans. Then, after incorporation into the dental adhesive, an S. mutans biofilm model was used to grow 48 h-mature biofilms. The biofilms grown over the formulated materials were assessed by colony-forming unit (CFU) counting assay and fluorescence microscopy staining. In addition, the cytotoxicity was evaluated. Samples were subjected to 10,000 thermal cycles for aging and evaluated by UTS, µTBS, and CFU. Incorporating BDMDAC did not increase the cytotoxicity or change the physical properties when the mass fraction of the BDMDAC was 1–5 wt.%. The UTS of BDMDAC-doped adhesives was not impaired immediately or over time. A significant bacterial reduction was obtained for the mass fraction of the BDMDAC greater than 3 wt.%. However, the BDMDAC-doped adhesives did not offer an antibacterial effect after artificial aging. The overall results indicate that the BDMDAC strategy has the potential to control of microbial growth of cariogenic planktonic cells and biofilms. However, other new technological approaches are needed to overcome the deleterious effect of BDMDAC release over time such as those based on the principle of drug delivery systems whereby the BDMDAC is transported on microparticles or core shells, providing tangible benefits to oral health over time. Full article

The effect of a surface pre-reacted glass ionomer (S-PRG)-containing sealant on the demineralization inhibition and remineralization of intact enamel adjacent to the sealant material was investigated. BeautiSealant (BTS, S-PRG sealant, Shofu), Teeth Mate F-12.0 (TMF, fluoride-releasing sealant, Kuraray Noritake Dental), and an experimental silica-filler sealant were investigated. After pH cycling for 10 days, the enamel surface adjacent to the sealant material was observed using confocal laser microscopy and scanning electron microscopy. The polymerized sealant disks were immersed in a demineralized solution (pH: 4.3) to measure pH change. The enamel specimens with polymerized sealant disks were additionally immersed in demineralized solution, followed by energy-dispersive X-ray spectroscopy. The demineralized area of BTS was significantly smaller than that of TMF and SS (p < 0.05). The surfaces adjacent to the sealant of TMF and SS were demineralized, while the surface of BTS was comparatively intact. An increase in pH values were observed in the BTS and TMF groups. Enamel surfaces presented an inhibition of demineralization for BTS and TMF, but not for SS. Fluoride uptake from the polymerized sealant was greater for BTS than for TMF. The S-PRG-containing sealant showed a buffering ability, demineralization inhibition, promotion of remineralization, and it can be advised for clinical applications. Full article

Rapid advances in nanotechnologies are driving the revolution in controlled drug delivery. However, heterogeneous barriers, such as blood circulation and cellular barriers, prevent the drug from reaching the cellular target in complex physiologic environments. In this review, we discuss the precise design of nanotechnologies to enhance the efficacy, quality, and durability of drug delivery. For drug delivery in vivo, drugs loaded in nanoplatforms target particular sites in a spatial- and temporal-dependent manner. Advances in stimuli-responsive nanoparticles and carbon-based drug delivery platforms are summarized. For transdermal drug delivery systems, specific strategies including microneedles and hydrogel lead to a sustained release efficacy. Moreover, we highlight the current limitations of clinical translation and an incentive for the future development of nanotechnology-based drug delivery. Full article

Traumatic, tumoral, and infectious bone defects are common in clinics, and create a big burden on patient’s families and society. Calcium phosphate (CaP)-based biomaterials have superior properties and have been widely used for bone defect repair, due to their similarities to the inorganic components of human bones. The biological performance of CaPs, as a determining factor for their applications, are dependent on their physicochemical properties. Hydroxyapatite (HAP) as the most thermally stable crystalline phase of CaP is mostly used in the form of ceramics or composites scaffolds with polymers. Nanostructured CaPs with large surface areas are suitable for drug/gene delivery systems. Additionally, CaP scaffolds with hierarchical nano-/microstructures have demonstrated excellent ability in promoting bone regeneration. This review focuses on the relationships and interactions between the physicochemical/biological properties of CaP biomaterials and their species, sizes, and morphologies in bone regeneration, including synthesis strategies, structure control, biological behavior, and the mechanisms of CaP in promoting osteogenesis. This review will be helpful for scientists and engineers to further understand CaP-based biomaterials (CaPs), and be useful in developing new high-performance biomaterials for bone repair. Full article

Liposomes, due to their safety profile and targeting ability, are among the most studied nanocarriers as antimicrobial delivery systems. However, due to lack of stability and the non-specific interaction of liposomes with cells and proteins, their use is relatively limited. Aiming to overcome these drawbacks, it was envisaged that incorporation of ulvan, a bioactive marine sulfated polysaccharide isolated from green algae, in liposomes could improve their physicochemical properties and overall stability. Thus, we initially studied the interactions of ulvan with neutral, negatively, and positively charged lipids using Differential Scanning Calorimetry and subsequently, based on the obtained results, we prepared the respective ulvan–containing neutral and charged liposomes, where ulvan interacts with both lipid chains and polar groups in the liposomal bilayer. In a further step, we entrapped in the liposomes fusidic acid, used as a model antibacterial drug, and proceeded with the evaluation of their antibacterial activity against Staphylococcus aureus. The physicochemical properties (size and ζ-potential), stability, morphology, and entrapment efficiency of the prepared liposomal formulations were determined. Full article

Bone infections are a key health challenge with dramatic consequences for affected patients. In dentistry, periodontitis is a medically compromised condition for efficient dental care and bone grafting, the success of which depends on whether the surgical site is infected or not. Present treatments involve antibiotics associated with massive bacterial resistance effects, urging for the development of alternative antibacterial strategies. In this work, we established a safe-by-design bone substitute approach by combining bone-like apatite to peroxide ions close to natural in vivo oxygenated species aimed at fighting pathogens. In parallel, bone-like apatites doped with Ag⁺ or co-doped Ag⁺/peroxide were also prepared for comparative purposes. The compounds were thoroughly characterized by chemical titrations, FTIR, XRD, SEM, and EDX analyses. All doped apatites demonstrated significant antibacterial properties toward four major pathogenic bacteria involved in periodontitis and bone infection, namely Porphyromonas gingivalis (P. gingivalis), Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Fusobacterium nucleatum (F. nucleatum), and S. aureus. By way of complementary tests to assess protein adsorption, osteoblast cell adhesion, viability and IC₅₀ values, the samples were also shown to be highly biocompatible. In particular, peroxidated apatite was the safest material tested, with the lowest IC₅₀ value toward osteoblast cells. We then demonstrated the possibility to associate such doped apatites with two biocompatible polymers, namely gelatin and poly(lactic-co-glycolic) acid PLGA, to prepare, respectively, composite 2D membranes and 3D scaffolds. The spatial distribution of the apatite particles and polymers was scrutinized by SEM and µCT analyses, and their relevance to the field of bone regeneration was underlined. Such bio-inspired antibacterial apatite compounds, whether pure or associated with (bio)polymers are thus promising candidates in dentistry and orthopedics while providing an alternative to antibiotherapy. Full article

The objective of this study was to evaluate the impacts of different sandblasting procedures in acid etching of Ti6Al4V surfaces on osteoblast cell behavior, regarding various physicochemical and topographical parameters. Furthermore, differences in osteoblast cell behavior between cpTi and Ti6Al4V SA surfaces were evaluated. Sandblasting and subsequent acid etching of cpTi and Ti6Al4V discs was performed with Al₂O₃ grains of different sizes and with varying blasting pressures. The micro- and nano-roughness of the experimental SA surfaces were analyzed via confocal, atomic force and scanning electron microscopy. Surface free energy and friction coefficients were determined. hFOB 1.19 cells were seeded to evaluate adhesion, proliferation and osteoblastic differentiation for up to 12 d via crystal violet assays, MTT assays, ALP activity assays and Alizarin Red staining assays. Differences in blasting procedures had significant impacts on surface macro- and micro-topography. The crystal violet assay revealed a significant inverse relationship between blasting grain size and hFOB cell growth after 7 days. This trend was also visible in the Alizarin Red assays staining after 12 d: there was significantly higher biomineralization visible in the group that was sandblasted with smaller grains (F180) when compared to standard-grain-size groups (F70). SA samples treated with reduced blasting pressure exhibited lower hFOB adhesion and growth capabilities at initial (2 h) and later time points for up to 7 days, when compared to the standard SA surface, even though micro-roughness and other relevant surface parameters were similar. Overall, etched-only surfaces consistently exhibited equivalent or higher adhesion, proliferation and differentiation capabilities when compared to all other sandblasted and etched surfaces. No differences were found between cpTi and Ti6Al4V SA surfaces. Subtle modifications in the blasting protocol for Ti6Al4V SA surfaces significantly affect the proliferative and differentiation behavior of human osteoblasts. Surface roughness parameters are not sufficient to predict osteoblast behavior on etched Ti6Al4V surfaces. Full article

Antibacterial resistance is observed as a public health issue around the world. Every day, new resistance mechanisms appear and spread over the world. For that reason, it is imperative to improve the treatment schemes that have been developed to treat infections caused by wound infections, for instance, Staphylococcus epidermidis (S. epidermidis), Proteus mirabilis (P. mirabilis), and Acinetobacter baumannii (A. baumannii). In this case, we proposed a method that involves mixing the Gentamicin (Gen) with iron oxide nanoparticles (Fe₃O₄ NPs) and a polymer (polyethylene glycol (PEG)) with Fe₃O₄ NPs. X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), energy dispersive X-ray (EDX), scanning electron microscope (SEM), and transmission electron microscope (TEM) were used to characterize Fe₃O₄ NPs. Zeta potential and dynamic light scattering (DLS) were also assessed. The antibacterial activity of Fe₃O₄ NPs, Fe₃O₄ NPs+PEG, Fe₃O₄ NPs+Gen, and Fe₃O₄ NPs+PEG+Gen composites was investigated. The results showed a significant improvement in the antibacterial activity of nanoparticles against bacterial isolates, especially for the Fe₃O₄ NPs+PEG+Gen as the diameter of the inhibition zone reached 26.33 ± 0.57 mm for A. baumannii, 25.66 ± 0.57 mm for P. mirabilis, and 23.66 ± 0.57 mm for S. epidermidis. The Fe₃O₄ NPs, Fe₃O₄ NPs+PEG, Fe₃O₄+Gen, and Fe₃O₄+PEG+Gen also showed effectiveness against the biofilm produced by these isolated bacteria. The minimum inhibitory concentration (MIC) of Fe₃O₄ NPs for S. epidermidis was 25 µg mL⁻¹ and for P. mirabilis and A. baumannii was 50 µg mL⁻¹. The findings suggest that the prepared nanoparticles could be potential therapeutic options for treating wound infections caused by S. epidermidis, P. mirabilis, and A. baumannii. Full article

Nanomedicines have been a major research focus in the past two decades and are increasingly emerging in a broad range of clinical applications. However, a proper understanding of their biodistribution is required to further progress the field of nanomedicine. For this, imaging methods to monitor the delivery and therapeutic efficacy of nanoparticles are urgently needed. At present, optical imaging is the most common method used to study the biodistribution of nanomaterials, where the unique properties of nanomaterials and advances in optical imaging can jointly result in novel methods for optimal monitoring of nanomaterials in preclinical animal models. This review article aims to give an introduction to nanomedicines and their translational impact to highlight the potential of optical imaging to study the biodistribution of nanoparticles and to monitor the delivery and therapeutic efficacy at the preclinical level. After introducing both domains, the review focuses on different techniques that can be used to overcome some intrinsic limitations of optical imaging and how this can specifically benefit nanoparticle studies. Finally, we point out some important key features of nanoparticles that currently hinder their full potential in the clinic and how the advances in optical imaging can help to provide us with the information needed to further boost the clinical translation and expand the field of nanomedicines. Full article

Wounds are characterised by an anatomical disruption of the skin; this leaves the body exposed to opportunistic pathogens which contribute to infections. Current wound healing bandages do little to protect against this and when they do, they can often utilise harmful additions. Historically, plant-based constituents have been extensively used for wound treatment and are proven beneficial in such environments. In this work, the essential oil of clove bud (Syzygium aromaticum) was incorporated in a polycaprolactone (PCL) solution, and 44.4% (v/v) oil-containing fibres were produced through pressurised gyration. The antimicrobial activity of these bandage-like fibres was analysed using in vitro disk diffusion and the physical fibre properties were also assessed. The work showed that advantageous fibre morphologies were achieved with diameters of 10.90 ± 4.99 μm. The clove bud oil fibres demonstrated good antimicrobial properties. They exhibited inhibition zone diameters of 30, 18, 11, and 20 mm against microbial colonies of C. albicans, E. coli, S. aureus, and S. pyogenes, respectively. These microbial species are commonly problematic in environments where the skin barrier is compromised. The outcomes of this study are thus very promising and suggest that clove bud oil is highly suitable to be applied as a natural sustainable alternative to modern medicine. Full article

Although laser irradiation and implantoplasty (IP) are both treatment options for peri-implantitis, no studies have yet combined these two treatment solutions. The aim of this study was to identify the effect of an Er, Cr: YSGG laser on the IP surface. In experiment 1, TiUnite anodized surface implants were treated with an Er, Cr: YSGG laser at 0.5 to 2 W on the panel energy setting and 20 Hz under water irrigation. In experiment 2, all implant surfaces were treated with the IP procedure first, then irradiated with the Er, Cr: YSGG laser. All samples were analyzed by stereomicroscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), and surface topography. Stereomicroscopy and SEM revealed no obvious surface change at any energy setting once the surface was polished with the IP procedure, whereas damage was caused to the TiUnite original implant surface when the Er, Cr: YSGG laser panel energy was set at 1 W or higher. EDS showed no significant difference in element composition once the surface was polished with the IP procedure, while a compositional change was detected when the Er, Cr: YSGG laser panel energy was set to 0.5 W or higher to irradiate the original TiUnite surface. Surface roughness may be related to laser irradiation energy, but no significant changes occurred following IP. These results indicated that the Er, Cr: YSGG laser may have little effect on the post-IP surface compared with the virgin TiUnite surface. Full article

This study aimed to determine the most suitable recombinant fortilin and evaluate the biological activities of glass ionomer cement (GIC) incorporated with fortilin on human dental pulp stem cells (hDPSCs). Full-length and three fragments of Penaeus merguiensis fortilin were cloned and examined for their proliferative and cytoprotective effects on hDPSCs by MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. Human DPSCs were cultured with GIC supplemented with fortilin, tricalcium phosphate, or a combination of tricalcium phosphate and fortilin, designated as GIC + FL, GIC + TCP, and GIC + TCP + FL, respectively (n = 4 for each group). At given time points, hDPSCs were harvested and analyzed by MTT, quantitative reverse transcription polymerase chain reaction, alkaline phosphatase activity, and Alizarin Red assays. The full-length fortilin promoted cell proliferation and significantly increased cell survival. This protein was subsequently added into the GIC along with tricalcium phosphate to investigate the biological activities. All experimental groups showed reduced cell viability after treatment with modified GICs on days 1 and 3. The GIC + TCP + FL group significantly promoted odontoblastic differentiation at particular time points. In addition, alkaline phosphatase activity and calcium phosphate deposit were markedly increased in the GIC + TCP + FL group. Among all experimental groups, the GIC incorporated with fortilin and tricalcium phosphate demonstrated the best results on odontogenic differentiation and mineral deposition in hDPSCs. Full article

In this work, polyethyleneimine (PEI)-grafted chitosan (Chi-g-PEI) was prepared for the fabrication of layer-by-layer (LBL) films for use in sustained-drug-delivery applications. Chi-g-PEI and polyacrylic acid (PAA) multilayer films were formed using the LBL technique. Methylene blue (MB) was used as a model drug for the investigation of loading and release capabilities of the LBL films. Characterizations of the synthesized copolymer were performed using Fourier-transform infrared spectroscopy (FTIR), Nuclear magnetic resonance spectroscopy (NMR), Thermogravimetric analysis (TGA), and X-ray Powder Diffraction (XRD) techniques, and the thickness of the LBL films was measured using Atomic force microscopy (AFM). The drug-loading and -release behaviors of the LBL films were assessed using a UV–visible spectrophotometer. The results showed that the loading capacity and release rate of MB were affected by ionic strength and pH. In addition, it was demonstrated that PEI-grafted chitosan is a good candidate for the assembling of LBL films for drug-delivery applications. Full article

Silicon nitride (Si₃N₄) is a promising biomaterial, currently used in spinal fusion implants. Such implants should result in high vertebral union rates without major complications. However, pseudarthrosis remains an important complication that could lead to a need for implant replacement. Making silicon nitride implants more bioactive could lead to higher fusion rates, and reduce the incidence of pseudarthrosis. In this study, it was hypothesized that creating a highly negatively charged Si₃N₄ surface would enhance its bioactivity without affecting the antibacterial nature of the material. To this end, samples were thermally, chemically, and thermochemically treated. Apatite formation was examined for a 21-day immersion period as an in-vitro estimate of bioactivity. Staphylococcus aureus bacteria were inoculated on the surface of the samples, and their viability was investigated. It was found that the thermochemically and chemically treated samples exhibited enhanced bioactivity, as demonstrated by the increased spontaneous formation of apatite on their surface. All modified samples showed a reduction in the bacterial population; however, no statistically significant differences were noticed between groups. This study successfully demonstrated a simple method to improve the in vitro bioactivity of Si₃N₄ implants while maintaining the bacteriostatic properties. Full article

The objective of this study is to replace a traditional methacrylate-based primer (glycine, N-(2-hydroxy-3-(2-methyl-1-oxo-2-propenyl)propyl)-N-(4-methylphenyl) monosodium salt, NTG-GMA) with a hydrolytically stable ether-based primer (glycine, N-2-hydroxy-3-(4-vinylbenzyloxy)-propyl-N-(4-methylphenyl), monosodium salt, NTG-VBGE). The performance and durability of bonding composites to detin of two primers combined with methacrylate-based or ether-based adhesives were evaluated using shear bond strength (SBS) and micro-tensile bond strength (μTBS) combined with thermal cycling. The hydrolysis resistance of NTG-VBGE against hydrolysis was tested by challenging primed hydroxyapatite crystals with an esterase. The hydrophilicity of the primers and the resin spreading kinetics of adhesives on primed dentin were characterized by water contact angle measurements. The new primer NTG-VBGE was found to be compatible with both methacrylate-based adhesives and ether-based adhesives. The highest μTBS values were found in the test group of NTG-VBGE and ether-based adhesive, which was consistent with the resin spreading kinetics results. The more hydrophobic and hydrolytically stable primer/adhesive achieved improved dentin infiltration and bonding strength, suggesting significant potential for further developing dental restorative materials with extended service life. Full article

Metallic ions have been widely investigated and incorporated into bone substitutes for bone regeneration owing to their superior capacity to induce angiogenesis and osteogenesis. Exosomes are key paracrine mediators that play a crucial role in cell-to-cell communication. However, the role of exosomes in metallic ion-induced bone formation and their underlying mechanisms remain unclear. Thus, this review systematically analyzes the effects of metallic ions and metallic ion-incorporated biomaterials on exosome secretion from mesenchymal stem cells (MSCs) and macrophages, as well as the effects of secreted exosomes on inflammation, angiogenesis, and osteogenesis. In addition, possible signaling pathways involved in metallic ion-mediated exosomes, followed by bone regeneration, are discussed. Despite limited investigation, metallic ions have been confirmed to regulate exosome production and function, affecting immune response, angiogenesis, and osteogenesis. Although the underlying mechanism is not yet clear, these insights enrich our understanding of the mechanisms of the metallic ion-induced microenvironment for bone regeneration, benefiting the design of metallic ion-incorporated implants. Full article

Diseases affecting the central nervous system (CNS) are among the most disabling and the most difficult to cure due to the presence of the blood–brain barrier (BBB) which represents an impediment from a therapeutic and diagnostic point of view as it limits the entry of most drugs. The use of biocompatible polymer nanoparticles (NPs) as vehicles for targeted drug delivery to the brain arouses increasing interest. However, the route of administration of these vectors remains critical as the drug must be delivered without being degraded to achieve a therapeutic effect. An innovative approach for the administration of drugs to the brain using polymeric carriers is represented by the nose-to-brain (NtB) route which involves the administration of the therapeutic molecule through the neuro-olfactory epithelium of the nasal mucosa. Nasal administration is a non-invasive approach that allows the rapid transport of the drug directly to the brain and minimizes its systemic exposure. To date, many studies involve the use of polymer NPs for the NtB transport of drugs to the brain for the treatment of a whole series of disabling neurological diseases for which, as of today, there is no cure. In this review, various types of biodegradable polymer NPs for drug delivery to the brain through the NtB route are discussed and particular attention is devoted to the treatment of neurological diseases such as Glioblastoma and neurodegenerative diseases. Full article

The aim of this study was to evaluate the use of a new porcine bone graft in rat calvaria bone defects. Critical defects were surgically created in 24 rats that were divided into four experimental groups according to defect filling (n = 6): Control Group (CG)—blood clot; Porcine Bone Group (PG)—porcine-derived bone substitute; (BG): Bio-Oss Group (BG)–chemically and heat-treated bovine graft; Bonefill Group (BFG)—chemically treated bovine bone substitute. Euthanasia of the animals occurred 30 days after the surgery, and the area of the original surgical defect and the surrounding tissues were removed for micro-CT and histomorphometric analysis. In the micro-CT evaluation, the PG presented statistically significant differences (p < 0.05) in comparison to the CG, BG and BFG, for the parameters percentage of Bone Volume (BV/TV), Surface Bone Density (BS/TV), Number of Trabeculae (Tb.N) and Bone Connectivity (Conn), but not for Total Porosity (Po.tot) and Trabecular Thickness (Tb.Th). The histomorphometric analysis showed that the PG presented similar results to the BG regarding newly formed bone extension and to the BG and BFG regarding newly formed bone area. The porcine-derived graft presented superior microtomographic and histomorphometric results when compared to the two bovine bone substitutes. Full article

The aim of this study was to evaluate the bone response to two different implant surfaces on sinus lift procedures in rabbits. Bilateral sinus lifting with inorganic bovine bone associated with collagen membrane and immediate implantation were performed in 16 rabbits. Custom mini-implants were randomly installed in the prepared sites: one side received a double acid-etched (DAE) surface and the other a nano-hydroxyapatite (NHA) surface. The animals were euthanized 30 and 60 days after surgery, and biopsies were collected for microtomographic and histomorphometric analysis. After 30 days, no intra- and inter-group statistical differences were observed in microtomographic analysis, while at 60 days, bone analysis showed statistically significant differences between groups (p < 0.05) for all the evaluated parameters. Histomorphometric analysis showed, after 30 days, mean % of Bone-to-Implant Contact (BIC) for DAE and NHA of 31.70 ± 10.42% vs. 40.60 ± 10.22% (p > 0.05), respectively; for % of Bone Area Fraction Occupancy (BAFO), mean values were 45.43 ± 3.597% for DAE and 57.04 ± 5.537% for NHA (p < 0.05). After 60 days, mean %BIC and %BAFO for DAE and NHA implants were statistically significant (p < 0.05). The NHA surface showed superior biological features compared to the DAE treatment, promoting higher bone formation around the implants in an experimental model of bone repair in a grafted area. Full article

The present research aimed to characterize soft tissue implants that were prepared with the use of crosslinked hyaluronic acid (HA) using two different crosslinkers and multiple reagent concentrations, alone or in combination with fibrin. The effect of the implants was evaluated in an in vivo mouse model, after 4 weeks in one group and after 12 weeks in the other. The explants were compared using analytical methods, evaluating microscopic images, and a histology analysis. The kinetics of the degradation and remodeling of explants were found to be greatly dependent on the concentration and type of crosslinker; generally, divinyl sulfone (DVS) resists degradation more effectively compared to butanediol diglycidyl ether (BDDE). The presence of fibrin enhances the formation of blood vessels, and the infiltration of cells and extracellular matrix. In summary, if the aim is to create a soft tissue implant with easier degradation of the HA content, then the use of 2–5% BDDE is found to be optimal. For a longer degradation time, 5% DVS is the more suitable crosslinker. The use of fibrin was found to support the biological process of remodeling, while keeping the advances of HA in void filling, enabling the parallel degradation and remodeling processes. Full article

In regenerative medicine and tissue engineering, the possibility to: (I) customize the shape and size of scaffolds, (II) develop highly mimicked tissues with a precise digital control, (III) manufacture complex structures and (IV) reduce the wastes related to the production process, are the main advantages of additive manufacturing technologies such as three-dimensional (3D) bioprinting. Specifically, this technique, which uses suitable hydrogel-based bioinks, enriched with cells and/or growth factors, has received significant consideration, especially in cartilage tissue engineering (CTE). In this field of interest, it may allow mimicking the complex native zonal hyaline cartilage organization by further enhancing its biological cues. However, there are still some limitations that need to be overcome before 3D bioprinting may be globally used for scaffolds’ development and their clinical translation. One of them is represented by the poor availability of appropriate, biocompatible and eco-friendly biomaterials, which should present a series of specific requirements to be used and transformed into a proper bioink for CTE. In this scenario, considering that, nowadays, the environmental decline is of the highest concerns worldwide, exploring naturally-derived hydrogels has attracted outstanding attention throughout the scientific community. For this reason, a comprehensive review of the naturally-derived hydrogels, commonly employed as bioinks in CTE, was carried out. In particular, the current state of art regarding eco-friendly and natural bioinks’ development for CTE was explored. Overall, this paper gives an overview of 3D bioprinting for CTE to guide future research towards the development of more reliable, customized, eco-friendly and innovative strategies for this field of interest. Full article

Over the last two decades, bio-polymer fibers have attracted attention for their uses in gene therapy, tissue engineering, wound-healing, and controlled drug delivery. The most commonly used bio-polymers are bio-sourced synthetic polymers such as poly (glycolic acid), poly (lactic acid), poly (e-caprolactone), copolymers of polyglycolide and poly (3-hydroxybutyrate), and natural polymers such as chitosan, soy protein, and alginate. Among all of the bio-polymer fibers, alginate is endowed with its ease of sol–gel transformation, remarkable ion exchange properties, and acid stability. Blending alginate fibers with a wide range of other materials has certainly opened many new opportunities for applications. This paper presents an overview on the modification of alginate fibers with nano-particles, adhesive peptides, and natural or synthetic polymers, in order to enhance their properties. The application of alginate fibers in several areas such as cosmetics, sensors, drug delivery, tissue engineering, and water treatment are investigated. The first section is a brief theoretical background regarding the definition, the source, and the structure of alginate. The second part deals with the physico-chemical, structural, and biological properties of alginate bio-polymers. The third part presents the spinning techniques and the effects of the process and solution parameters on the thermo-mechanical and physico-chemical properties of alginate fibers. Then, the fourth part presents the additives used as fillers in order to improve the properties of alginate fibers. Finally, the last section covers the practical applications of alginate composite fibers. Full article

Background: Cancer is a common disease in dogs, with a growing incidence related to the age of the animal. Nanotechnology is being employed in the veterinary field in the same manner as in human therapy. Aim: This review focuses on the application of biocompatible nanocarriers for the treatment of canine cancer, paying attention to the experimental studies performed on dogs with spontaneously occurring cancer. Methods: The most important experimental investigations based on the use of lipid and non-lipid nanosystems proposed for the treatment of canine cancer, such as liposomes and polymeric nanoparticles containing doxorubicin, paclitaxel and cisplatin, are described and their in vivo fate and antitumor features discussed. Conclusions: Dogs affected by spontaneous cancers are useful models for evaluating the efficacy of drug delivery systems containing antitumor compounds. Full article

In this work, for the first time, polyamide 12 (PA12) nanocomposites with binary inclusions in material extrusion (MEX) 3D printing were developed. The aim was to achieve an enhanced mechanical response with the addition of titanium nitride (TiN) and antibacterial performance with the addition of copper (Cu) or cuprous oxide (Cu₂O), towards the development of multi-functional nanocomposite materials, exploiting the 3D printing process benefits. The prepared nanocomposites were fully characterized for their mechanical properties. The thermal properties were also investigated. Morphological characterization was performed with atomic force microscopy (AFM) and scanning electron microscopy (SEM). The antibacterial performance was investigated with an agar-well diffusion screening process. Overall, the introduction of these nanofillers induced antibacterial performance in the PA12 matrix materials, while at the same time, the mechanical performance was significantly increased. The results of the study show high potential for expanding the areas in which 3D printing can be used. Full article

The aim of the present in vitro study was to evaluate the intratubular penetration of three bioceramic sealers in root canal retreatment. Here, 30 single-rooted human teeth were instrumented with the Protaper Universal system and filled with gutta-percha and the epoxy-resin-based sealer AH Plus mixed with rhodamine B. After two weeks in a humid environment, they were re-instrumented with Reciproc Blue and divided into three groups according to the endodontic sealer to be used in the re-filling (n = 10): G1: CeraSeal, G2: TotalFill BC Sealer, G3: TotalFill BC Sealer HiFlow. For the filling, a single cone technique was used, and the respective sealers were mixed with fluorescein. The roots were then sectioned at 2, 5, and 8 mm (apical, medial, and coronal measurement points, respectively) from the apex, and the dentinal tubule penetration depth and percentage of penetration around the canal perimeter were evaluated by means of confocal laser scanning microscopy (CLSM). Penetration between groups was compared using the Kruskal−Wallis test, and within each group using the Wilcoxon test. Statistical significance was established at p < 0.05. A non-significant reduction was found in the penetration depths and in a percentage of penetration around the canal perimeter between AH Plus and the tested calcium-silicate-based sealers (p > 0.05). Consequently, this reduction may not affect the three-dimensional seal of the root canal system in a negative manner. The penetration depth and percentage of penetration around the canal perimeter at both the root canal treatment and retreatment were significantly reduced from the coronal to apical points in all groups (p < 0.05). Full article

Polymeric nanoparticles have been introduced as a delivery vehicle for active compounds in a broad range of medical applications due to their biocompatibility, stability, controlled release of active compounds, and reduced toxicity. The oral route is the most used approach for delivery of biologics to the body. The homeostasis and function of oral cavity tissues are dependent on the activity of stem cells. The present work focuses, for the first time, on the interaction between two types of polymeric nanoparticles, poly (lactic-co-glycolic acid) or PLGA and PLGA/chitosan, and two stem cell populations, oral keratinocyte stem cells (OKSCs) and stem cells from human exfoliated deciduous teeth (SHEDs). The main results show that statistical significance was observed in OKSCs uptake when compared with normal keratinocytes and transit amplifying cells after 24 h of incubation with 5 and 10 µg/mL PLGA/chitosan. The CD117⁺ SHED subpopulation incorporated more PLGA/chitosan nanoparticles than nonseparated SHED. The uptake for PLGA/chitosan particles was better than for PLGA particles with longer incubation times, yielding better results in both cell types. The present results demonstrate that nanoparticle uptake depends on stem cell type, incubation time, particle concentration, and surface properties. Full article

In the present study, the structural, morphological, and in vivo biocompatibility of un-doped and boron (B)-doped strontium apatite (SrAp) nanoparticles were investigated. Biomaterials were fabricated using the hydrothermal process. The structural and morphological characterizations of the fabricated nanoparticles were performed by XRD, FT-IR, FE-SEM, and EDX. Their biocompatibility was investigated by placing them in defects in rat tibiae in vivo. The un-doped and B-doped SrAp nanoparticles were successfully fabricated. The produced nanoparticles were in the shape of nano-rods, and the dimensions of the nano-rods decreased as the B ratio increased. It was observed that the structural and morphological properties of strontium apatite nanoparticles were affected by the contribution of B. A stoichiometric Sr/P ratio of 1.67 was reached in the 5% B-doped sample (1.68). The average crystallite sizes were 34.94 nm, 39.70 nm, 44.93 nm, and 48.23 nm in un-doped, 1% B-doped, 5% B-doped, and 10% B-doped samples, respectively. The results of the in vivo experiment revealed that the new bone formation and osteoblast density were higher in the groups with SrAp nanoparticles doped with different concentrations of B than in the control group, in which the open defects were untreated. It was observed that this biocompatibility and the new bone formation were especially elevated in the B groups, which added high levels of strontium were added. The osteoblast density was higher in the group in which the strontium element was placed in the opened bone defect compared with the control group. However, although new bone formation was slightly higher in the strontium group than in the control group, the difference was not statistically significant. Furthermore, the strontium group had the highest amount of fibrotic tissue formation. The produced nanoparticles can be used in dental and orthopedic applications as biomaterials. Full article

Dental pulp is essential for the development and long-term preservation of teeth. Dental trauma and caries often lead to pulp inflammation. Vital pulp therapy using dental pulp-capping materials is an approach to preserving the vitality of injured dental pulp. Most pulp-capping materials used in clinics have good biocompatibility to promote mineralization, but their anti-inflammatory effect is weak. Therefore, the failure rate will increase when dental pulp inflammation is severe. The present study developed an amorphous calcium phosphate/poly (L-lactic acid)-poly (lactic-co-glycolic acid) membrane compounded with aspirin (hereafter known as ASP/PLGA-ASP/ACP/PLLA-PLGA). The composite membrane, used as a pulp-capping material, effectively achieved the rapid release of high concentrations of the anti-inflammatory drug aspirin during the early stages as well as the long-term release of low concentrations of aspirin and calcium/phosphorus ions during the later stages, which could repair inflamed dental pulp and promote mineralization. Meanwhile, the composite membrane promoted the proliferation of inflamed dental pulp stem cells, downregulated the expression of inflammatory markers, upregulated the expression of mineralization-related markers, and induced the formation of stronger reparative dentin in the rat pulpitis model. These findings indicate that this material may be suitable for use as a pulp-capping material in clinical applications. Full article

The wound healing process is much more complex than just the four phases of hemostasis, inflammation, proliferation, and maturation. Three-dimensional (3D) scaffolds made of biopolymers or ECM molecules using bioprinting can be used to promote the wound healing process, especially for complex 3D tissue lesions like chronic wounds. Here, a 3D-printed mold has been designed to produce customizable collagen type-I sheets containing human umbilical vein endothelial cells (HUVECs) and adipose stromal cells (ASCs) for the first time. In these 3D collagen sheets, the cellular activity leads to a restructuring of the collagen matrix. The upregulation of the growth factors Serpin E1 and TIMP-1 could be demonstrated in the 3D scaffolds with ACSs and HUVECs in co-culture. Both growth factors play a key role in the wound healing process. The capillary-like tube formation of HUVECs treated with supernatant from the collagen sheets revealed the secretion of angiogenic growth factors. Altogether, this demonstrates that collagen type I combined with the co-cultivation of HUVECs and ACSs has the potential to accelerate the process of angiogenesis and, thereby, might promote wound healing. Full article

Biomaterials are used as implants for bone and dental disabilities. However, wear particles from the implants cause osteolysis following total joint arthroplasty (TJA). Ceramic implants are considered safe and elicit a minimal response to cause periprosthetic osteolysis. However, few reports have highlighted the adverse effect of ceramic particles such as alumina (Al₂O₃) on various cell types. Hence, we aimed to investigate the effect of Al₂O₃ particles on osteoprogenitors. A comparative treatment of Al₂O₃, Ti, and UHMWPE particles to osteoprogenitors at a similar concentration of 200 μg/mL showed that only Al₂O₃ particles were able to suppress the early and late differentiation markers of osteoprogenitors, including collagen synthesis, alkaline phosphatase (ALP) activity and mRNA expression of Runx2, OSX, Col1α, and OCN. Al₂O₃ particles even induced inflammation and activated the NFkB signaling pathway in osteoprogenitors. Moreover, bone-forming signals such as the WNT/β-catenin signaling pathway were inhibited by the Al₂O₃ particles. Al₂O₃ particles were found to induce the mRNA expression of WNT/β-catenin signaling antagonists such as DKK2, WIF, and sFRP1 several times in osteoprogenitors. Taken together, this study highlights a mechanistic view of the effect of Al₂O₃ particles on osteoprogenitors and suggests therapeutic targets such as NFĸB and WNT signaling pathways for ceramic particle-induced osteolysis. Full article

The use of biocompatible and biodegradable porous scaffolds produced via additive manufacturing is one of the most common approaches in tissue engineering. The geometric design of tissue engineering scaffolds (e.g., pore size, pore shape, and pore distribution) has a significant impact on their biological behavior. Fluid flow dynamics are important for understanding blood flow through a porous structure, as they determine the transport of nutrients and oxygen to cells and the flushing of toxic waste. The aim of this study is to investigate the impact of the scaffold architecture, pore size and distribution on its biological performance using Computational Fluid Dynamics (CFD). Different blood flow velocities (BFV) induce wall shear stresses (WSS) on cells. WSS values above 30 mPa are detrimental to their growth. In this study, two scaffold designs were considered: rectangular scaffolds with uniform square pores (300, 350, and 450 µm), and anatomically designed circular scaffolds with a bone-like structure and pore size gradient (476–979 µm). The anatomically designed scaffolds provided the best fluid flow conditions, suggesting a 24.21% improvement in the biological performance compared to the rectangular scaffolds. The numerical observations are aligned with those of previously reported biological studies. Full article

To stabilize drugs physisorbed on the surface of hydroxyapatite (HAp) nanoparticles and prevent burst release, these nanoparticles are commonly coated with polymers. Bioactive HAp, however, becomes shielded from the surface of such core/shell entities, which partially defeats the purpose of using it. The goal of this study was to assess the biological and pharmacokinetic effects of inverting this classical core/shell structure by coating poly(lactic-co-glycolic acid) (PLGA) spheres with HAp nanoparticles. The HAp shell did not hinder the release of vancomycin; rather, it increased the release rate to a minor degree, compared to that from undecorated PLGA spheres. The decoration of PLGA spheres with HAp induced lesser mineral deposition and lesser upregulation of osteogenic markers compared to those induced by the composite particles where HAp nanoparticles were embedded inside the PLGA spheres. This was explained by homeostatic mechanisms governing the cell metabolism, which ensure than the sensation of a product of this metabolism in the cell interior or exterior is met with the reduction in the metabolic activity. The antagonistic relationship between proliferation and bone production was demonstrated by the higher proliferation rate of cells challenged with HAp-coated PLGA spheres than of those treated with PLGA-coated HAp. It is concluded that the overwhelmingly positive response of tissues to HAp-coated biomaterials for bone replacement is unlikely to be due to the direct induction of new bone growth in osteoblasts adhering to the HAp coating. Rather, these positive effects are consequential to more elementary aspects of cell attachment, mechanotransduction, and growth at the site of contact between the HAp-coated material and the tissue. Full article

The repair and reconstruction of tracheal defects is a challenging clinical problem. Due to the wide choice of materials and structures, weaving technology has shown unique advantages in simulating the multilayer structure of the trachea and providing reliable performance. Currently, most woven stent-based stents focus only on the effect of materials on stent performance while ignoring the direct effect of woven process parameters on stent performance, and the advantages of weaving technology in tissue regeneration have not been fully exploited. Therefore, this review will introduce the effects of stent materials and fabric construction on the performance of tracheal stents, focusing on the effects of weaving process parameters on stent performance. We will summarize the problems faced by woven stents and possible directions of development in the hope of broadening the technical field of artificial trachea preparation. Full article

In this work, an electrically conductive composite based on thermoplastic polyimide and graphene was obtained and used as a bioelectrode for electrical stimulation of human dermal fibroblasts. The values of the electrical conductivity of the obtained composite films varied from 10⁻¹⁵ to 10² S/m with increasing graphene content (from 0 to 5.0 wt.%). The characteristics of ionic and electronic currents flowing through the matrix with the superposition of cyclic potentials ± 100 mV were studied. The high stability of the composite was established during prolonged cycling (130 h) in an electric field with a frequency of 0.016 Hz. It was established that the composite films based on polyimide and graphene have good biocompatibility and are not toxic to fibroblast cells. It was shown that preliminary electrical stimulation increases the proliferative activity of human dermal fibroblasts in comparison with intact cells. It is revealed that an electric field with a strength E = 0.02–0.04 V/m applied to the polyimide films containing 0.5–3.0 wt.% of the graphene nanoparticles activates cellular processes (adhesion, proliferation). Full article

The availability of biomaterials able to counteract bacterial colonization is one of the main requirements of functional implants and medical devices. Herein, we functionalized hydroxyapatite (HA) with tungsten oxide (WO₃) nanoparticles in the aim to obtain composite materials with improved biological performance. To this purpose, we used HA, as well as HA functionalized with polyacrilic acid (HAPAA) or poly(ethylenimine) (HAPEI), as supports and polyvinylpyrrolidone (PVP) as stabilizing agent for WO₃ nanoparticles. The number of nanoparticles loaded on the substrates was determined through Molecular Plasma-Atomic Emission Spectroscopy and is quite small, so it cannot be detected through X-ray diffraction analysis. It increases from HAPAA, to HA, to HAPEI, in agreement with the different values of zeta potential of the different substrates. HRTEM and STEM images show the dimensions of the nanoparticles are very small, less than 1 nm. In physiological solution HA support displays a greater tungsten cumulative release than HAPEI, despite its smaller loaded amount. Indeed, WO₃ nanoparticles-functionalized HA exhibits a remarkable antibacterial activity against the Gram-positive Staphylococcus aureus in absence of cytotoxicity, which could be usefully exploited in the biomedical field. Full article

The uses of implantable medical devices are safer and more common since sterilization methods and techniques were established a century ago; however, device-associated infections (DAIs) are still frequent and becoming a leading complication as the number of medical device implantations keeps increasing. This urges the world to develop instructive prevention and treatment strategies for DAIs, boosting the studies on the design of antibacterial surfaces. Every year, studies associated with DAIs yield thousands of publications, which here are categorized into four groups, i.e., antibacterial surfaces with long-term efficacy, cell-selective capability, tailored responsiveness, and immune-instructive actions. These innovations are promising in advancing the solution to DAIs; whereas most of these are normally quite preliminary “proof of concept” studies lacking exact clinical scopes. To help identify the flaws of our current antibacterial designs, clinical features of DAIs are highlighted. These include unpredictable onset, site-specific incidence, and possibly involving multiple and resistant pathogenic strains. The key point we delivered is antibacterial designs should meet the specific requirements of the primary functions defined by the “intended use” of an implantable medical device. This review intends to help comprehend the complex relationship between the device, pathogens, and the host, and figure out future directions for improving the quality of antibacterial designs and promoting clinical translations. Full article

A fine control over different dimensional scales is a challenging target for material science since it could grant control over many properties of the final material. In this study, we developed a multivariable additive manufacturing process, direct ink write printing, to control different architectural features from the nano- to the millimeter scale during extrusion. Chitin-based gel fibers with a water content of around 1500% were obtained extruding a polymeric solution of chitin into a counter solvent, water, inducing instant solidification of the material. A certain degree of fibrillar alignment was achieved basing on the shear stress induced by the nozzle. In this study we took into account a single variable, the nozzle’s internal diameter (NID). In fact, a positive correlation between NID, fibril alignment, and mechanical resistance was observed. A negative correlation with NID was observed with porosity, exposed surface, and lightly with water content. No correlation was observed with maximum elongation (~50%), and the scaffold’s excellent biocompatibility, which appeared unaltered. Overall, a single variable allowed a customization of different material features, which could be further tuned, adding control over other aspects of the synthetic process. Moreover, this manufacturing could be potentially applied to any polymer. Full article

After bleaching, enamel surfaces are damaged, contributing to erosion and tooth sensitivity. Although fluoride is used after bleaching to try and revert alterations, it is not capable of repairing tooth structure. This study compared the effect of a self-assembly peptide (P₁₁-4), with and without fluoride, and sodium fluoride (NaF 2%) on the Knoop microhardness (KHN) and surface roughness (Ra (μm)) of bleached enamel with an in-office bleaching regimen. Enamel blocks of bovine teeth (5 × 5 × 2 mm) with standardized surface hardness were bleached with 35% carbamide peroxide, following the manufacturer’s instructions. The teeth were randomly divided into the following groups (n = 7) according to post-bleaching treatment: no treatment (negative control) (C-); 2% NaF (NaF); Curodont™ Repair (Repair); and Curodont™ Protect (Protect). Specimens were stored in artificial saliva at 37 °C. To evaluate the effect of the post-bleaching treatments, KHN and Ra were measured before bleaching (baseline) and 24 h and 7 days after bleaching. Data were submitted to repeated measures ANOVA and Bonferroni tests (α = 0.05). There were significant interactions between the study factors (p = 0.001). After 7 days, Repair (572.50 ± 79.04) and Protect (583.00 ± 74.76) specimens showed increased surface KHN, with values higher than the NaF (465.50 ± 41.50) and C- (475.22 ± 58.95) baseline values. There was no significant difference in KHN at 24 h among groups (p = 0.587). At 24 h after bleaching, Repair was significantly different from all groups (p < 0.05). Repair showed the lowest Ra (μm) values (0.133 ± 0.035). After seven days, there was no significant difference in Ra values among groups when compared to the baseline. The use of P₁₁-4-based materials after bleaching resulted in the fastest recovery to baseline enamel properties. Full article

Graphene-based materials have attracted much attention due to their fascinating properties such as hydrophilicity, high dispersion in aqueous media, robust size, high biocompatibility, and surface functionalization ability due to the presence of functional groups and interactions with biomolecules such as proteins and nucleic acid. Modified methods were developed for safe, direct, inexpensive, and eco-friendly synthesis. However, toxicity to the environment and animal health has been reported, raising concerns about their utilization. This review focuses primarily on the synthesis methods of graphene-based materials already developed and the unique properties that make them so interesting for different applications. Different applications are presented and discussed with particular emphasis on biological fields. Furthermore, antimicrobial potential and the factors that affect this activity are reviewed. Finally, questions related to toxicity to the environment and living organisms are revised by highlighting factors that may interfere with it. Full article

The fabrication of patient-specific scaffolds for bone substitutes is possible through extrusion-based 3D printing of calcium phosphate cements (CPC) which allows the generation of structures with a high degree of customization and interconnected porosity. Given the brittleness of this clinically approved material, the stability of open-porous scaffolds cannot always be secured. Herein, a multi-technological approach allowed the simultaneous combination of CPC printing with melt electrowriting (MEW) of polycaprolactone (PCL) microfibers in an alternating, tunable design in one automated fabrication process. The hybrid CPC+PCL scaffolds with varying CPC strand distance (800–2000 µm) and integrated PCL fibers featured a strong CPC to PCL interface. While no adverse effect on mechanical stiffness was detected by the PCL-supported scaffold design; the microfiber integration led to an improved integrity. The pore distance between CPC strands was gradually increased to identify at which critical CPC porosity the microfibers would have a significant impact on pore bridging behavior and growth of seeded cells. At a CPC strand distance of 1600 µm, after 2 weeks of cultivation, the incorporation of PCL fibers led to pore coverage by a human mesenchymal stem cell line and an elevated proliferation level of murine pre-osteoblasts. The integrated fabrication approach allows versatile design adjustments on different levels. Full article