Editor’s Choice Articles

The extent and patterns of foreign body reaction (FBR) influence the function and feasibility of biomaterials. Polysaccharides, as an important biomaterial category, have received increasing attention in diverse biomaterials design and biomedical applications due to their excellent polymeric and biocompatible characteristics. Their biological effects are usually associated with their monosaccharide composition or functional groups, yet the contribution of their glycan structure is still unknown. Herein, two glucomannans, similar in composition and molecular weight with differences in glycan structure, linear-chain (Konjac glucomannan, KGM), and branched-chain (Bletilla striata polysaccharide, BSP), were adopted to explore the host–biomaterials interaction. After acetyl modification, these polysaccharides were fabricated into electrospun scaffolds to reduce the impacts derived from the physical properties and surface morphology. According to a systematic study of their biological effects on immune cells and host response in a subcutaneous implantation model in vivo, it was revealed that acetyl KGM (acKGM) scaffolds caused a stronger FBR than acetyl BSP materials. Additionally, acKGM could stimulate macrophages to release pro-inflammatory cytokines, suggesting the influence of sugar chain arrangement on FBR and providing clues for the fine regulation of immune response and novel biomaterials design. Full article

In this work, the micro-arc oxidation method is used to fabricate surface-modified complex-structured titanium implant coatings to improve biocompatibility. Depending on the utilized electrolyte solution and micro-arc oxidation process parameters, three different types of coatings (one of them—oxide, another two—calcium phosphates) were obtained, differing in their coating thickness, crystallite phase composition and, thus, with a significantly different biocompatibility. An analytical approach based on X-ray computed tomography utilizing software-aided coating recognition is employed in this work to reveal their structural uniformity. Electrochemical studies prove that the coatings exhibit varying levels of corrosion protection. In vitro and in vivo experiments of the three different micro-arc oxidation coatings prove high biocompatibility towards adult stem cells (investigation of cell adhesion, proliferation and osteogenic differentiation), as well as in vivo biocompatibility (including histological analysis). These results demonstrate superior biological properties compared to unmodified titanium surfaces. The ratio of calcium and phosphorus in coatings, as well as their phase composition, have a great influence on the biological response of the coatings. Full article

Dental replacements are placed between the abutment teeth. The exceptions are two-unit bridges, as they are supported by a single tooth prepared only on one side of the missing tooth. The presented study deals with an analysis of a pressure force action on two-unit bridges placed in the frontal part (20 samples), where the pressure action is lower, and in the distal part (20 samples), where the pressure action is higher. A CAD program by 3Shape was used for digital designing with two different gap settings, 10 μm (20 samples) and 30 μm (20 samples). Two-unit bridges were attached to the prepared tooth using two types of dental cement (20/20 samples), which were selected for their physical and bioactive properties. All two-unit bridges (a total of 80 samples) were fabricated from CoCr alloys on Mlab cusing R by applying the Selective Laser Melting (SLM) technology. Mechanical testing was performed using the Inspekt5 table blue. The obtained data were used to verify the hypotheses—a difference between both types of cement (A ≠ B), a difference between the frontal and distal two-unit bridges (F ≠ D) and a difference between the gap sizes (10 ≠ 30). To confirm the given theories, data were statistically evaluated using the F-test and subsequent t-tests. The resulting p-value was compared with the level of significance (α = 0.05). A statistical evaluation revealed a significant difference between the compared groups; however, no explicit correlation between the individual groups of specimens was identified. Full article

Multiple-pathogen periodontal disease necessitates a local release and concentration of antibacterial medication to control inflammation in a particular location of the mouth cavity. Therefore, it is necessary to effectively load and deliver medicine/antibiotics to treat numerous complex bacterial infections. This study developed chlorhexidine (CHX)/polycaprolactone (PCL) nanofiber membranes with controlled release properties as periodontal dressings to prevent or treat oral disorders. Electrostatic spinning was adopted to endow the nanofiber membranes with a high porosity, hydrophilicity, and CHX loading capability. The release of CHX occurred in a concentration-dependent manner. The CHX/PCL nanofiber membranes exhibited good biocompatibility with human periodontal ligament stem cells, with cell viability over 85% in each group via CCK-8 assay and LIVE/DEAD staining; moreover, the good attachment of the membrane was illustrated by scanning electron microscopy imaging. Through the agar diffusion assay, the nanofiber membranes with only 0.075 wt% CHX exhibited high antibacterial activity against three typical oral infection-causing bacteria: Porphyromonas gingivalis, Enterococcus faecalis, and Prevotella intermedia. The results indicated that the CHX/PCL nanofiber holds great potential as a periodontal dressing for the prevention and treatment periodontal disorders associated with bacteria. Full article

Objective: To compare healing of collagenated and non-collagenated xenografts used for maxillary sinus floor elevation. Materials and Methods: Two different xenografts were used: deproteinized bovine bone (DBBM group) and collagenated corticocancellous porcine bone (collagenated group). Healing was studied after 2, 4, and 8 weeks. The loss of dimensions of the elevated area and the percentages of new bone, xenograft remnants, osteoclastic zones, vessels, inflammatory infiltrates, and soft tissues were analyzed. Three regions were evaluated: close to the bone walls (bone wall region), subjacent the sinus mucosa (submucosa region), and the center of the elevated area (middle region). The primary variables were the percentage of new bone and xenograft remnants. Results: Between 2 and 8 weeks, the elevated areas showed a reduction of 16.3% and 52.2% in the DBBM and collagenated groups, respectively (p < 0.01 between the two areas after 8 weeks). After 8 weeks, the highest content of new bone was observed in the bone wall region, which was higher in the collagenated group than in the DBBM group (41.6% and 28.6%, respectively; p < 0.01). A similar quantity of new bone was found between the two groups in other regions. A higher percentage of vessels in all regions evaluated (p < 0.01) and soft tissue in the sub-mucosa region (p < 0.05) was found in the collagenated group than in the DBBM group. Conclusions: The present study showed that both xenografts allowed new bone formation. In comparison with the non-collagenated xenograft, the collagenated xenograft underwent higher resorption, resulting in greater shrinkage of the elevated space after sinus lifting and a higher content of new bone in the regions close to the bone walls. Clinical relevance: In this study, the region adjacent to the bone wall showed the highest new bone content. This region resembles the base of the sinus, closest to the sinus floor and walls, and is the most important region from a clinical point of view because it is where the implant will be installed. Residues of the biomaterial remained after 8 weeks of healing. Other reports have shown that these biomaterial residues may interfere with the integration of implants. Full article

Mesoporous silica SBA-15 was prepared via sol-gel synthesis and functionalized with different types of organosilanes containing various organic functional groups: (3-aminopropyl)triethoxysilane (SBA-15-NH₂), (3-mercaptopropyl)triethoxysilane (SBA-15-SH), triethoxymethylsilane (SBA-15-CH₃), triethoxyphenylsilane (SBA-15-Ph), and (3-isocynatopropyl)triethoxysilane (SBA-15-NCO). The prepared materials were investigated as drug delivery systems for naproxen. As model drugs, naproxen acid (HNAP) and its sodium salt (NaNAP) were used. Mentioned medicaments belong to the group of non-steroidal anti-inflammatory drugs (NSAIDs). The prepared materials were characterized by different analytical methods such as transmission electron microscopy (TEM), infrared spectroscopy (IR), nitrogen adsorption/desorption analysis (N₂), thermogravimetric analysis (TG), ¹H, ¹³C and ²³Na solid-state nuclear magnetic resonance spectroscopy (¹H, ¹³C and ²³Na ss-NMR). The abovementioned analytical techniques confirmed the successful grafting of functional groups to the SBA-15 surface and the adsorption of drugs after the impregnation process. The BET area values decreased from 927 m² g⁻¹ for SBA-15 to 408 m² g⁻¹ for SBA-15-NCO. After drug encapsulation, a more significant decrease in surface area was observed due to the filling of pores with drug molecules, while the most significant decrease was observed for the SBA-15-NH₂ material (115 m² g⁻¹ for NaNAP and 101 m² g⁻¹ for HNAP). By combining TG and nitrogen adsorption results, the occurrence of functional groups and the affinity of drugs to the carriers’ surface were calculated. The dominant factor was the volume of functional groups and intermolecular interactions. The highest drug affinity values were observed for phenyl and amine-modified materials (SBA-15-Ph = 1.379 μmol m⁻² mmol⁻¹ for NaNAP, 1.761 μmol m⁻² mmol⁻¹ for HNAP and SBA-15-NH₂ = 1.343 μmol m⁻² mmol⁻¹ for NaNAP, 1.302 μmol m⁻² mmol⁻¹ for HNAP) due to the formation of hydrogen bonds and π-π interactions, respectively. Drug release properties and kinetic studies were performed at t = 37 °C (normal human body temperature) in different media with pH = 2 as simulated human gastric fluid and pH = 7.4, which simulated a physiological environment. Determination of drug release quantity was performed with UV-VIS spectroscopy. The surface polarity, pH and naproxen form influenced the total released amount of drug. In general, naproxen sodium salt has a higher solubility than its acid form, thus significantly affecting drug release from surface-modified SBA-15 materials. Different pH conditions involved surface protonation and formation/disruption of intermolecular interactions, influencing both the release rate and the total released amount of naproxen. Different kinetic models, zero-order, first-order, Higuchi and Hixson–Crowell models, were used to fit the drug release data. According to the obtained experimental results, the drug release rates and mechanisms were determined. Full article

In the last few years, the progress made in the field of nanotechnology has allowed researchers to develop and synthesize nanosized materials with unique physicochemical characteristics, suitable for various biomedical applications. Amongst these nanomaterials, metal oxide nanoparticles (MONPs) have gained increasing interest due to their excellent properties, which to a great extent differ from their bulk counterpart. However, despite such positive advantages, a substantial body of literature reports on their cytotoxic effects, which are directly correlated to the nanoparticles’ physicochemical properties, therefore, better control over the synthetic parameters will not only lead to favorable surface characteristics but may also increase biocompatibility and consequently lower cytotoxicity. Taking into consideration the enormous biomedical potential of MONPs, the present review will discuss the most recent developments in this field referring mainly to synthesis methods, physical and chemical characterization and biological effects, including the pro-regenerative and antitumor potentials as well as antibacterial activity. Moreover, the last section of the review will tackle the pressing issue of the toxic effects of MONPs on various tissues/organs and cell lines. Full article

Cement augmentation of pedicle screws is one of the most promising approaches to enhance the anchoring of screws in the osteoporotic spine. To date, there is no ideal cement for pedicle screw augmentation. The purpose of this study was to investigate whether an injectable, bioactive, and degradable calcium sulfate/hydroxyapatite (CaS/HA) cement could increase the maximum pull-out force of pedicle screws in osteoporotic vertebrae. Herein, 17 osteoporotic thoracic and lumbar vertebrae were obtained from a single fresh-frozen human cadaver and instrumented with fenestrated pedicle screws. The right screw in each vertebra was augmented with CaS/HA cement and the un-augmented left side served as a paired control. The cement distribution, interdigitation ability, and cement leakage were evaluated using radiographs. Furthermore, pull-out testing was used to evaluate the immediate mechanical effect of CaS/HA augmentation on the pedicle screws. The CaS/HA cement presented good distribution and interdigitation ability without leakage into the spinal canal. Augmentation significantly enhanced the maximum pull-out force of the pedicle screw in which the augmented side was 39.0% higher than the pedicle-screw-alone side. Therefore, the novel biodegradable biphasic CaS/HA cement could be a promising material for pedicle screw augmentation in the osteoporotic spine. Full article

Hydroxyapatite (HA) layers are appropriate biomaterials for use in the modification of the surface of implants produced inter alia from a Ti6Al4V alloy. The issue that must be solved is to provide implants with appropriate biointegration properties, enabling the permanent link between them and bone tissues, which is not so easy with the HA layer. Our proposition is the use of the intermediate layer ((IL) = TiO₂, and titanate layers) to successfully link the HA coating to a metal substrate (Ti6Al4V). The morphology, structure, and chemical composition of Ti6Al4V/IL/HA systems were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy-dispersive X-ray spectrometry (EDS). We evaluated the apatite-forming ability on the surface of the layer in simulated body fluid. We investigated the effects of the obtained systems on the viability and growth of human MG-63 osteoblast-like cells, mouse L929 fibroblasts, and adipose-derived human mesenchymal stem cells (ADSCs) in vitro, as well as on their osteogenic properties. Based on the obtained results, we can conclude that both investigated systems reflect the physiological environment of bone tissue and create a biocompatible surface supporting cell growth. However, the nanoporous TiO₂ intermediate layer with osteogenesis-supportive activity seems most promising for the practical application of Ti6Al4V/TiO₂/HA as a system of bone tissue regeneration. Full article

Angiotensin converting enzyme (ACE) overactivation is one of the primary causes of hypertension, which leads to cardiovascular disorders all over the world. In the scientific world, nanosuspension is a novel area of study that could offer an alternative treatment for active pharmaceuticals that are not well soluble in water. Since active compounds’ bioavailability is reduced by their poor solubility, there are eventually fewer applications. Drug solubility, dissolving rate, and bioavailability are improved by nanosuspension, which shrinks medication particle size into the nanoscale range and boosts the surface area to volume ratio of the drug. There is a need to prepare Rauvolfia serpentina’s nanosuspension in order to get around some of the major challenges that it faces because of its poor solubility and wide range of biological activities. Using the antisolvent precipitation approach, a nanosuspension of Rauvolfia serpentina was created with hydroxy propyl methyl cellulose (HPMC). Rouvolfia serpentina nanosuspensions were prepared using a design of expert (DOE) approach, which allowed for the evaluation of key process parameters. To get an optimal sample, the effects of stabilizer concentration and anti-solvent volume on particle size, zeta potential, and PdI using CCD-RSM were investigated. Using the substrate Hippuryl-histidyl-leucine, the in vitro ACE inhibitory potential was assessed. On human erythrocytes, the safety of nanosuspension was evaluated in vitro. The ideal value of independent variables was discovered to be 0.25% w/v in order to achieve the desired response. Using scanning electron microscopy, the morphology of optimized nanosuspension was discovered to be rod-shaped (SEM). Compared to nanoformulation, crude extract had higher ACE inhibitory potential (83.11%). Human erythrocytes were found to be unaffected by nano-sized particles. Full article

Magnesium (Mg) alloys have recently attracted attention in biomedicine as biodegradable materials with non-toxic degradable products. Such compounds have become a frontier in the study of biodegradable materials because of their remarkable biomechanical compatibility and superior biocompatibility. The use of Mg-based implants reduces the negative consequences of permanent biological implants by eliminating the necessity for biomaterial surgery following the healing process. However, the quick deterioration, formation of considerable gas of hydrogen volumes and a rise in the body environment pH are obstacles in the application of Mg as an implant material. Hence, compelling advances for erosion resistance and biocompatibility of magnesium and its alloys are noteworthy. Surface modification may be a practical approach because it improves the erosion resistance compared with extensive preparation of a treated surface for progressed bone recovery and cell attachment. Coating produced by plasma electrolytic oxidation (PEO) seems a compelling method in order to enhance magnesium and the properties of its alloys. PEO-formed coatings cannot provide long-term protection in the physiological environment due to their porous nature. Thus, a polymer coating is applied on the porous PEO-formed coating, which is steadily applied on the surface. Polymer coatings improve the biocompatibility properties of Mg and its alloys and increase corrosion resistance. In this article, the most recent advancements in PEO/polymer composite coatings are reviewed, and the biocompatibility of such coatings is examined. Full article

Introduction: The UVC-irradiation (“UV-photofunctionalization”) of titanium dental implants has proved to be capable of removing carbon contamination and restoring the ability of titanium surfaces to attract cells involved in the process of osteointegration, thus significantly enhancing the biocompatibility of implants and favoring the post-operative healing process. To what extent the effect of UVC irradiation is dependent on the type or the topography of titanium used, is still not sufficiently established. Objective: The present study was aimed at analyzing the effects of UV-photofunctionalization on the TiO₂ topography, as well as on the gene expression patterns and the biological activity of osteogenic cells, i.e., osteogenic precursors cultured in vitro in the presence of different titanium specimens. Methodology: The analysis of the surface roughness was performed by atomic force microscopy (AFM) on machined surface grade 2, and sand-blasted/acid-etched surface grades 2 and 4 titanium specimens. The expression of the genes related with the process of healing and osteogenesis was studied in the MC3T3-E1 pre-osteoblastic murine cells, as well as in MSC murine stem cells, before and after exposure to differently treated TiO₂ surfaces. Results: The AFM determinations showed that the surface topographies of titanium after the sand-blasting and acid-etching procedures, look very similar, independently of the grade of titanium. The UVC-irradiation of the TiO₂ surface was found to induce an increase in the cell survival, attachment and proliferation, which was positively correlated with an increased expression of the osteogenesis-related genes Runx2 and alkaline phosphatase (ALP). Conclusion: Overall, our findings expand and further support the current view that UV-photofunctionalization can indeed restore biocompatibility and osteointegration of TiO₂ implants, and suggest that this at least in part occurs through a stimulation of the osteogenic differentiation of the precursor cells. Full article

Magnesium (Mg) and its alloys are considered to be biodegradable metallic biomaterials for potential orthopedic implants. While the osteogenic properties of Mg alloys have been widely studied, few reports focused on developing a bifunctional Mg implant with osteogenic and angiogenic properties. Herein, a Mg-Sc-Sr alloy was developed, and this alloy’s angiogenesis and osteogenesis effects were evaluated in vitro for the first time. X-ray Fluorescence (XRF), X-ray diffraction (XRD), and metallography images were used to evaluate the microstructure of the developed Mg-Sc-Sr alloy. Human umbilical vein/vascular endothelial cells (HUVECs) were used to evaluate the angiogenic character of the prepared Mg-Sc-Sr alloy. A mix of human bone-marrow-derived mesenchymal stromal cells (hBM-MSCs) and HUVEC cell cultures were used to assess the osteogenesis-stimulating effect of Mg-Sc-Sr alloy through alkaline phosphatase (ALP) and Von Kossa staining. Higher ALP activity and the number of calcified nodules (27% increase) were obtained for the Mg-Sc-Sr-treated groups compared to Mg-treated groups. In addition, higher VEGF expression (45.5% increase), tube length (80.8% increase), and number of meshes (37.9% increase) were observed. The Mg-Sc-Sr alloy showed significantly higher angiogenesis and osteogenic differentiation than pure Mg and the control group, suggesting such a composition as a promising candidate in bone implants. Full article

Titanium has excellent biocompatibility and good corrosion resistance and is extensively used in dental implants and denture bases. However, pure titanium lacks the strength for use in dental prostheses that require relatively high strength. We developed 15 different types of Ti-Nb-Cu alloys and investigated their alloy phases and mechanical properties, including tensile and yield strength, elongation after fracture, and Vickers hardness. The alloy phases of Ti-8%Nb-2%Cu and Ti-13%Nb-2%Cu were α + β, while those of Ti-5%Nb-5%Cu and Ti-10%Nb-5%Cu were α + Ti₂Cu. The tensile strength and hardness of these alloys were significantly higher than those of titanium; however, their elongation was less. In particular, the yield strength of these alloys was more than twice that of titanium. These differences in mechanical properties are attributable to solid–solution strengthening and precipitation strengthening. Other compositions with an alloy phase of α + β + Ti₂Cu or β + Ti₂Cu had high hardness but not high strength. These results suggest that the Ti-8%Nb-2%Cu, Ti-5%Nb-5%Cu, Ti-13%Nb-2%Cu, and Ti-10%Nb-5%Cu alloys can be applied to dental prostheses, which are subject to very high forces from accessories such as long-span bridges, clasps, implant-retained superstructures, and narrow-diameter implants. Full article

The diverse biological properties of platinum nanoparticles (PtNPs) make them ideal for use in the development of new tools in therapy, diagnostics, and other biomedical purposes. “Green” PtNPs synthesis is of great interest as it is eco-friendly, less energy-consuming and minimizes the amount of toxic by-products. This review is devoted to the biosynthesis properties of platinum nanoparticles based on living organisms (bacteria, fungi, algae, and plants) use. The participation of various biological compounds in PtNPs synthesis is highlighted. The biological activities of “green” platinum nanoparticles (antimicrobial, anticancer, antioxidant, etc.), the proposed mechanisms of influence on target cells and the potential for their further biomedical application are discussed. Full article

In this work, the microstructure, phase state, texture, superelastic and mechanical properties of a Ti–18Zr–15Nb (at. %) shape memory alloy subjected to a combined thermomechanical treatment, including hot rotary forging with either air cooling or water quenching and post-deformation annealing are studied. It was revealed that the main structural component of the deformed and annealed alloy is BCC β-phase. With an increase in the forging temperature from 600 to 700 °C, the average grain size increases from 5.4 to 17.8 µm for the air-cooled specimens and from 3.4 to 14.7 µm for the water-quenched specimens. Annealing at 525 °C after forging at 700 °C with water quenching leads to the formation of a mixed statically and dynamically polygonized substructure of β-phase. In this state, the alloy demonstrates the best combination of functional properties in this study: a Young’s modulus of ~33 GPa, an ultimate tensile strength of ~600 MPa and a superelastic recovery strain of ~3.4%. Full article

Vat photopolymerization (VPP) is an additive manufacturing process commonly used in medical applications. This work aims, for the first time in the literature, to extend and enhance the performance of a commercial medical-grade resin for the VPP process, with the development of nanocomposites, using Copper (Cu) nanoparticles as the additive at two different concentrations. The addition of the Cu nanoparticles was expected to enhance the mechanical properties of the resin and to enable biocidal properties on the nanocomposites since Cu is known for its antibacterial performance. The effect of the Cu concentration was investigated. The nanocomposites were prepared with high-shear stirring. Specimens were 3D printed following international standards for mechanical testing. Their thermal and spectroscopic response was also investigated. The morphological characteristics were examined. The antibacterial performance was evaluated with an agar well diffusion screening process. The experimental results were analyzed with statistical modeling tools with two control parameters (three levels each) and eleven response parameters. Cu enhanced the mechanical properties in all cases studied. 0.5 wt.% Cu nanocomposite showed the highest improvement (approximately 11% in tensile and 10% in flexural strength). The antibacterial performance was sufficient against S. aureus and marginal against E. coli. Full article

Background: It has been shown in rabbit models that the sinus mucosa in contact with graft particles might experience a progressive thinning and perforations. The phenomenon depends on the graft used. Hence, the aim of the present study was to compare the damaging effects of a synthetic of a xenogeneic graft. Methods: Forty New Zealand rabbits received a bilateral sinus elevation. Both sinuses of twenty rabbits were grafted with a biphasic 60% hydroxyapatite and 40% β-tricalcium phosphate while the other twenty received a deproteinized bovine bone mineral graft. Thinned sites (<40 µm) and perforations on the mucosa in contact with graft particles were evaluated after 2 and 10 weeks (ten animals each period). The width of the pseudostratified epithelium was also measured as control. Results: After 2 weeks of healing, 61 thinned sites were detected in the Synthetic group and 49 in the Xenogeneic group. After 10 weeks, the number of thinned mucosae increased to 79 sites in the Synthetic group (p = 0.222 between periods), and to 114 sites in the Xenogeneic group (p = 0.030 between groups; p = 0.001 between periods). Perforations were few in the 2-week period, two in two sinuses out of 20 in the Synthetic group, and four in two sinuses out of 20 in the Xenogeneic group (p = 0.721). In the 10-week period, the perforations increased to eight in the Synthetic group, distributed in six sinuses out of 20, and to sixteen in the Xenogeneic group, distributed in 11 sinuses out of 20 (p = 0.082). The pseudostratified epithelium presented a reduced width at the thinned sites. Conclusions: The contact with synthetic or xenogeneic grafts will induce thinning and possible perforations of the sinus mucosa. This effect will increase over time, and it is stronger at the xenogeneic than the synthetic graft. Full article

The antibacterial properties of nanomaterials (NMs) can be exploited in a range of consumer products (e.g., wound dressings, food packaging, textiles, medicines). There is also interest in the exploitation of NMs as treatments for infectious diseases to help combat antibiotic resistance. Whilst the antibacterial activity of NMs has been assessed in vitro and in vivo in numerous studies, the methodology used is very varied. Indeed, while numerous approaches are available to assess the antibacterial effect of NMs in vitro, they have not yet been systematically assessed for their suitability and sensitivity for testing NMs. It is therefore timely to consider what assays should be prioritised to screen the antibacterial properties of NMs. The majority of existing in vitro studies have focused on investigating the antibacterial effects exhibited by silver (Ag) NMs and have employed a limited range of assays. We therefore compared the antibacterial effects of copper oxide (CuO) NMs to Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis at various concentrations (12.5–200 µg/mL) using a battery of tests (well and disc diffusion, plate counts—time-kill method, optical density measurement—OD, Alamar Blue and live/dead viability assays, and quantitative polymerase chain reaction). CuO NMs were most toxic to B. subtilis and E. coli, while P. aeruginosa was the least sensitive strain. All assays employed detected the antibacterial activity of CuO NMs; however, they varied in their sensitivity, time, cost, technical difficulty and requirement for specialized equipment. In the future, we suggest that a combination of approaches is used to provide a robust assessment of the antibacterial activity of NMs. In particular, we recommend that the time-kill and OD assays are prioritised due to their greater sensitivity. We also suggest that standard operating protocols are developed so that the antibacterial activity of NMs can be assessed using a harmonised approach. Full article

Strontium acetate is applied for dental hypersensitivity treatment; however, the use of strontium carbonates for this purpose has not been described. The use of Sr-carbonate nanoparticles takes advantage of both the benefits of strontium on dentin mineralization and the abrasive properties of carbonates. Here in, we aimed to synthesize strontium carbonate and strontium-substituted calcium carbonate nanoparticles and test them as potential compounds in active dentifrices for treating dental hypersensitivity. For this, SrCO₃, Sr_0.5Ca_0.5CO₃, and CaCO₃ nanoparticles were precipitated using Na₂CO₃, SrCl₂, and/or CaCl₂ as precursors. Their morphology and crystallinity were evaluated by electron microscopy (SEM) and X-ray diffraction, respectively. The nanoparticles were added to a poly (vinyl alcohol) gel and used to brush dentin surfaces isolated from human third molars. Dentin chemical composition before and after brushing was investigated by infrared spectroscopy (FTIR) and X-ray dispersive energy spectroscopy. Dentin tubule morphology, obliteration, and resistance of the coatings to acid attack were investigated by SEM and EDS. The cytotoxicity and ability of the particles to trigger the mineralization of hDPSCs in vitro were studied. Dentin brushed with the nanoparticles was coated by a mineral layer that was also able to penetrate the tubules, while CaCO₃ remained as individual particles on the surface. FTIR bands related to carbonate groups were intensified after brushing with either SrCO₃ or Sr_0.5Ca_0.5CO₃. The shift of the phosphate-related FTIR band to a lower wavenumber indicated that strontium replaced calcium on the dentin structure after treatment. The coating promoted by SrCO₃ or Sr_0.5Ca_0.5CO₃ resisted the acid attack, while calcium and phosphorus were removed from the top of the dentin surface. The nanoparticles were not toxic to hDPSCs and elicited mineralization of the cells, as revealed by increased mineral nodule formation and enhanced expression of COL1, ALP, and RUNX2. Adding Sr_0.5Ca_0.5CO₃ as an active ingredient in dentifrices formulations may be commercially advantageous since this compound combines the well-known abrasive properties of calcium carbonate with the mineralization ability of strontium, while the final cost remains between the cost of CaCO₃ and SrCO₃. The novel Sr_0.5Ca_0.5CO₃ nanoparticles might emerge as an alternative for the treatment of dental hypersensitivity. Full article

Several desensitizers routinely used clinically for dentin hypersensitivity are expected to inhibit demineralization. This study aimed to evaluate the effectiveness of sealing materials in inhibiting demineralization and increasing fluorine (F) uptake by acid-treated root surfaces. Five noncarious extracted human teeth were used to produce specimens. Three different fluoride-containing materials, namely “MS Coat F” (MS), “MS Coat Hys Block Gel” (HS), and CTX2 Varnish (FV), were used herein. Each material was applied to the demineralized root surface. Single sections were obtained from each specimen. All surfaces of each specimen, except the polished surface, were covered with wax and immersed in an automatic pH cycling system for 2 weeks. Fluorine and calcium distributions in the carious lesions of each specimen were evaluated using proton-induced gamma emission (PIGE) and X-ray (PIXE) techniques, respectively. Dentin demineralization was analyzed using transverse microradiography (TMR) before and after pH cycling. µPIXE/PIGE analysis demonstrated that all sample groups showed increased fluoride uptake on the root surface. TMR analysis revealed that both HS and FV showed significantly lower integrated mineral loss values than the control group. All three samples demonstrated a tendency towards increased fluoride uptake from fluoride-containing hypersensitivity desensitizers and a demineralization inhibition effect on root dentin. Full article

The objective of this study was to evaluate the influence of the titanium nanotube diameter and the effect of silicon carbide (SiC) coating on the proliferation and mineralization of pre-osteoblasts on titanium nanostructured surfaces. Anodized titanium sheets with nanotube diameters of 50 and 100 nm were used. The following four groups were tested in the study: (1) non-coated 50 nm nanotubes; (2) SiC-coated 50 nm titanium nanotubes; (3) non-coated 100 nm nanotubes and (4) SiC-coated 100 nm nanotubes. The biocompatibility and cytotoxicity of pre-osteoblasts were evaluated using a CellTiter-BlueCell Viability assay after 1, 2, and 3 days. After 3 days, cells attached to the surface were observed by SEM. Pre-osteoblast mineralization was determined using Alizarin-Red staining solution after 21 days of cultivation. Data were analyzed by a Kruskal–Wallis test at a p-value of 0.05. The results evidenced biocompatibility and non-cytotoxicity of both 50 and 100 nm diameter coated and non-coated surfaces after 1, 2 and 3 days. The statistical analysis indicates a statistically significant higher cell growth at 3 days (p < 0.05). SEM images after 3 days demonstrated flattened-shaped cells without any noticeable difference in the phenotypes between different diameters or surface treatments. After 21 days of induced osteogenic differentiation, the statistical analysis indicates significantly higher osteoblast calcification on coated groups of both diameters when compared with non-coated groups (p < 0.05). Based on these results, we can conclude that the titanium nanotube diameter did not play any role on cell viability or mineralization of pre-osteoblasts on SiC-coated or non-coated titanium nanotube sheets. The SiC coating demonstrated biocompatibility and non-cytotoxicity and contributed to an increase in osteoblast mineralization on titanium nanostructured surfaces when compared to non-coated groups. Full article

Inorganic biomaterials, including different types of metals and ceramics are widely used in various fields due to their biocompatibility, bioactivity, and bioresorbable capacity. In recent years, biomaterials have been used in biomedical and biological applications. Calcium phosphate (CaPs) compounds are gaining importance in the field of biomaterials used as a standalone material or in more complex structures, especially for bone substitutes and drug delivery systems. The use of multiple dopants into the structure of CaPs compounds can significantly improve their in vivo and in vitro activity. Among the general information included in the Introduction section, in the first section of this review paper, the authors provided a background on the development of hydroxyapatite, methods of synthesis, and its applications. The advantages of using different ions and co-ions for substitution into the hydroxyapatite lattice and their influence on physicochemical, antibacterial, and biological properties of hydroxyapatite are also presented in this section of the review paper. Larry Hench’s 45S5 Bioglass^®, commercially named 45S5, was the first bioactive glass that revealed a chemical bond with bone, highlighting the potential of this biomaterial to be widely used in biomedicine for bone regeneration. The second section of this article is focused on the development and current products based on 45S5 Bioglass^®, covering the historical evolution, importance of the sintering method, hybrid bioglass composites, and applications. To overcome the limitations of the original biomaterials, studies were performed to combine hydroxyapatite and 45S5 Bioglass^® into new composites used for their high bioactivity and improved properties. This particular type of combined hydroxyapatite/bioglass biomaterial is discussed in the last section of this review paper. Full article

The cornea and the skin are two organs that form the outer barrier of the human body. When either is injured (e.g., from surgery, physical trauma, or chemical burns), wound healing is initiated to restore integrity. Many cells are activated during wound healing. In particular, fibroblasts that are stimulated often transition into repair fibroblasts or myofibroblasts that synthesize extracellular matrix (ECM) components into the wound area. Control of wound ECM deposition is critical, as a disorganized ECM can block restoration of function. One of the most abundant structural proteins in the mammalian ECM is collagen. Collagen type I is the main component in connective tissues. It can be readily obtained and purified, and short analogs have also been developed for tissue engineering applications, including modulating the wound healing response. This review discusses the effect of several current collagen implants on the stimulation of corneal and skin wound healing. These range from collagen sponges and hydrogels to films and membranes. Full article

The continuous development of novel materials for biomedical applications is resulting in an increasingly better prognosis for patients. The application of more advanced materials relates to fewer complications and a desirable higher percentage of successful treatments. New, innovative materials being considered for biomedical applications are metallic alloys with an amorphous internal structure called metallic glasses. They are currently in a dynamic phase of development both in terms of formulating new chemical compositions and testing their properties in terms of intended biocompatibility. This review article intends to synthesize the latest research results in the field of biocompatible metallic glasses to create a more coherent picture of these materials. It summarizes and discusses the most recent findings in the areas of mechanical properties, corrosion resistance, in vitro cellular studies, antibacterial properties, and in vivo animal studies. Results are collected mainly for the most popular metallic glasses manufactured as thin films, coatings, and in bulk form. Considered materials include alloys based on zirconium and titanium, as well as new promising ones based on magnesium, tantalum, and palladium. From the properties of the examined metallic glasses, possible areas of application and further research directions to fill existing gaps are proposed. Full article

The tendon-to-bone interface is a special structure connecting the tendon and bone and is crucial for mechanical load transfer between dissimilar tissues. After an injury, fibrous scar tissues replace the native tendon-to-bone interface, creating a weak spot that needs to endure extra loading, significantly decreasing the mechanical properties of the motor system. Macrophages play a critical role in tendon-bone healing and can be divided into various phenotypes, according to their inducing stimuli and function. During the early stages of tendon-bone healing, M1 macrophages are predominant, while during the later stages, M2 macrophages replace the M1 macrophages. The two macrophage phenotypes play a significant, yet distinct, role in tendon-bone healing. Growing evidence shows that regulating the macrophage phenotypes is able to promote tendon-bone healing. This review aims to summarize the impact of different macrophages on tendon-bone healing and the current immunomodulatory biomaterials for regulating macrophages, which are used to promote tendon-bone healing. Although macrophages are a promising target for tendon-bone healing, the challenges and limitations of macrophages in tendon-bone healing research are discussed, along with directions for further research. Full article

The aim of this study was to compare the mechanical behaviors of three dental implant fixtures with different abutment connection designs. Three implant systems were studied: the control (BLX implant), test group 1 (TORX++ implant), and test group 2 (IU implant). Three samples from each group were subjected to static compression to fracture tests to determine the maximum fracture load, and twelve samples were exposed to fatigue tests that measured how many cycles the implants could endure before deformation or fracture. Detailed images of the implant–abutment assemblies were obtained using micro-computed tomography imaging, and fractured or deformed areas were observed using a scanning electron microscope (SEM). The mean maximum breaking loads of 578.45 ± 42.46 N, 793.26 ± 57.43 N, and 862.30 ± 74.25 N were obtained for the BLX, TORX++, and IU implants, respectively. All samples in the three groups withstood 5 × 10⁶ cycles at 50% of the nominal peak value, and different fracture points were observed. All abutment connection designs showed suitable mechanical properties for intraoral use. Microscopic differences in the fracture patterns may be due to the differences in the fixture design or abutment connection, and mechanical complications could be prevented by lowering the overload reaching the implant or preventing peri-implantitis. Full article

This work aims at the development and characterization of fluorapatite coatings, innovatively prepared by the hydrothermal method, aiming for enhanced osseointegration of titanium implants. Fluoride-containing coatings were prepared and characterized by scanning and transmission electron microscopy, Fourier-transform infrared spectroscopy—attenuated total reflectance, and X-ray photoelectron spectroscopy. The biological response was characterized by microtomographic evaluation and histomorphometric analysis upon orthotopic implantation in a translational rabbit experimental model. Physic-chemical analysis revealed the inclusion of fluoride in the apatite lattice with fluorapatite formation, associated with the presence of citrate species. The in vivo biological assessment of coated implants revealed an enhanced bone formation process—with increased bone-to-implant contact and bone volume. The attained enhancement of the osteogenic process may be attributable to the conjoined modulatory activity of selected fluoride and citrate levels within the produced coatings. In this regard, the production of fluorapatite coatings with citrate, through the hydrothermal method, entails a promising approach for enhanced osseointegration in implant dentistry and orthopedic applications. Full article

The multidisciplinary fields of tissue engineering and regenerative medicine have the potential to revolutionize the practise of medicine through the abilities to repair, regenerate, or replace tissues and organs with functional engineered constructs. To this end, tissue engineering combines scaffolding materials with cells and biologically active molecules into constructs with the appropriate structures and properties for tissue/organ regeneration, where scaffolding materials and biomolecules are the keys to mimic the native extracellular matrix (ECM). For this, one emerging way is to decellularize the native ECM into the materials suitable for, directly or in combination with other materials, creating functional constructs. Over the past decade, decellularized ECM (or dECM) has greatly facilitated the advance of tissue engineering and regenerative medicine, while being challenged in many ways. This article reviews the recent development of dECM for tissue engineering and regenerative medicine, with a focus on the preparation of dECM along with its influence on cell culture, the modification of dECM for use as a scaffolding material, and the novel techniques and emerging trends in processing dECM into functional constructs. We highlight the success of dECM and constructs in the in vitro, in vivo, and clinical applications and further identify the key issues and challenges involved, along with a discussion of future research directions. Full article

Biomaterials have been widely used as substitutes for diseased tissue in surgery and have gained great success and attention. At present, the biocompatibility of biomaterials such as PET woven fabrics is often evaluated both in vitro and in vivo. However, the current experimental methods cannot reveal the relationship between material surfaces and cell adhesion, and few research works have focused on the mechanisms of how the surface morphology of biomaterials affects cell adhesion and proliferation. Thus, it is meaningful to find out how the altered surfaces could affect cell adhesion and growth. In this study, we employed Ar low-temperature plasma treatment technology to create nano-grooves on the warp yarn of PET woven fabrics and seeded human umbellar vein endothelial cells (HUVEC) on these fabrics. We then assessed the O-glycan and N-glycan profiles of the cells grown on different structures of the polyester woven fabrics. The result showed that the surface morphology of polyester woven fabrics could affect the O-glycan profile but not the N-glycan profile of cultured HUVEC. Taken together, the study describes the effects of the surface morphology of biomaterial on the biosynthesis of cellular glycans and may provide new insights into the design and manufacture of biomaterials used as blood vessels based on the expression profiles of O-glycans on cultured cells. Full article

In this project, different calcification methods for collagen and collagen coatings were compared in terms of their applicability for 3D printing and production of collagen-coated scaffolds. For this purpose, scaffolds were printed from polycaprolactone PCL using the EnvisionTec 3D Bioplotter and then coated with collagen. Four different coating methods were then applied: hydroxyapatite (HA) powder directly in the collagen coating, incubation in 10× SBF, coating with alkaline phosphatase (ALP), and coating with poly-L-aspartic acid. The results were compared by ESEM, µCT, TEM, and EDX. HA directly in the collagen solution resulted in a pH change and thus an increase in viscosity, leading to clumping on the scaffolds. As a function of incubation time in 10× SBF as well as in ALP, HA layer thickness increased, while no coating on the collagen layer was apparently observed with poly-L-aspartic acid. Only ultrathin sections and TEM with SuperEDX detected nano crystalline HA in the collagen layer. Exclusively the incubation in poly-L-aspartic acid led to HA crystals within the collagen coating compared to all other methods where the HA layers formed in different forms only at the collagen layer. Full article

The surface stiffness of the microenvironment is a mechanical signal regulating biofilm growth without the risks associated with the use of bioactive agents. However, the mechanisms determining the expansion or prevention of biofilm growth on soft and stiff substrates are largely unknown. To answer this question, we used PDMS (polydimethylsiloxane, 9–574 kPa) and HA (hyaluronic acid gels, 44 Pa–2 kPa) differing in their hydration. We showed that the softest HA inhibited Escherichia coli biofilm growth, while the stiffest PDMS activated it. The bacterial mechanical environment significantly regulated the MscS mechanosensitive channel in higher abundance on the least colonized HA-44Pa, while Type-1 pili (FimA) showed regulation in higher abundance on the most colonized PDMS-9kPa. Type-1 pili regulated the free motion (the capacity of bacteria to move far from their initial position) necessary for biofilm growth independent of the substrate surface stiffness. In contrast, the total length travelled by the bacteria (diffusion coefficient) varied positively with the surface stiffness but not with the biofilm growth. The softest, hydrated HA, the least colonized surface, revealed the least diffusive and the least free-moving bacteria. Finally, this shows that customizing the surface elasticity and hydration, together, is an efficient means of affecting the bacteria’s mobility and attachment to the surface and thus designing biomedical surfaces to prevent biofilm growth. Full article

This paper reports the results of the large-scale field testing of composite materials with antibacterial properties in a tropical climate. The composite materials, based on a cotton fabric with a coating of metal oxide nanoparticles (TiO₂ and/or ZnO), were produced using high-power ultrasonic treatment. The antibacterial properties of the materials were studied in laboratory tests on solid and liquid nutrient media using bacteria of different taxonomic groups (Escherichia coli, Chromobacterium violaceum, Pseudomonas chlororaphis). On solid media, the coatings were able to achieve a >50% decrease in the number of bacteria. The field tests were carried out in a tropical climate, at the Climate test station “Hoa Lac” (Hanoi city, Vietnam). The composite materials demonstrated long-term antibacterial activity in the tropical climate: the number of microorganisms remained within the range of 1–3% in comparison with the control sample for the duration of the experiment (3 months). Ten of the microorganisms that most frequently occurred on the surface of the coated textiles were identified. The bacteria were harmless, while the fungi were pathogenic and contributed to fabric deterioration. Tensile strength deterioration was also studied, with the fabrics coated with metal oxides demonstrating a better preservation of their mechanical characteristics over time, (there was a 42% tensile strength decrease for the reference non-coated sample and a 21% decrease for the sample with a ZnO + CTAB coating). Full article

This study evaluated the efficacy of experimental TEGDMA-functionalized dicalcium phosphate dihydrate (T-DCPD) filler-based resin-based composites (RBC) in preventing caries lesions around the restoration margins (secondary caries, SC). Standardized Class-II cavities were made in sound molars with the cervical margin in dentin. Cavities were filled with a commercial resin-modified glass-ionomer cement (RMGIC) or experimental RBCs containing a bisGMA-TEGDMA resin blend and one of the following inorganic fractions: 60 wt.% Ba glass (RBC-0); 40 wt.% Ba glass and 20 wt.% T-DCPD (RBC-20); or 20 wt.% Ba glass and 40 wt.% T-DCPD (RBC-40). An open-system bioreactor produced Streptococcus mutans biofilm-driven SC. Specimens were scanned using micro-CT to evaluate demineralization depths. Scanning electron microscopy and energy-dispersive X-ray spectroscopy characterized the specimen surfaces, and antimicrobial activity, buffering effect, and ion uptake by the biofilms were also evaluated. ANOVA and Tukey’s tests were applied at p < 0.05. RBC-0 and RBC-20 showed SC development in dentin, while RBC-40 and RMGIC significantly reduced the lesion depth at the restoration margin (p < 0.0001). Initial enamel demineralization could be observed only around the RBC-0 and RBC-20 restorations. Direct antibiofilm activity can explain SC reduction by RMGIC, whereas a buffering effect on the acidogenicity of biofilm can explain the behavior of RBC-40. Experimental RBC with CaP-releasing functionalized T-DCPD filler could prevent SC with the same efficacy as F-releasing materials. Full article

The anterior cruciate ligament (ACL) is the most commonly injured intra-articular ligament of the knee. Due to its limited intrinsical healing potential and vascularization, injuries of the ACL do not heal satisfactorily, and surgical intervention is usually required. The limitations of existing reconstructive grafts and autologous transplants have prompted interest in tissue-engineered solutions. A tissue engineering scaffold for ACL reconstruction must be able to mimic the mechanical properties of the native ligament, provide sufficient porosity to promote cell growth of the neoligament tissue, and be biodegradable. This study investigates long-term biodegradable poly-ε-caprolactone (PCL)-based scaffolds for ACL replacement using the 3D hexagonal braiding technique. The scaffolds were characterized mechanically as well as morphologically. All scaffolds, regardless of their braid geometry, achieved the maximum tensile load of the native ACL. The diameter of all scaffolds was lower than that of the native ligament, making the scaffolds implantable with established surgical methods. The 3D hexagonal braiding technique offers a high degree of geometrical freedom and, thus, the possibility to develop novel scaffold architectures. Based on the findings of this study, the 3D-braided PCL-based scaffolds studied were found to be a promising construct for tissue engineering of the anterior cruciate ligament. Full article

Due to the growing problem of food and packaging waste, environmental awareness, and customer requirements for food safety, there is a great need for the development of innovative and functional packaging. Among these developments, the concept of active packaging is at the forefront. The shortcoming in this area is that there is still a lack of multifunctional concepts, as well as green approaches. Therefore, this work focuses on the development of active chemical substances of natural origin applied as a coating on polylactic acid (PLA) films. Biopolymer chitosan and plant extracts rich in phenolic compounds (blackberry leaves—Rubus fruticosus, needles of prickly juniper—Juniperus oxycedrus) obtained from plant biomass from Southeastern Europe were selected in this work. In order to increase the effectiveness of individual substances and to introduce multifunctionality, they were combined in the form of different colloidal structural formulations. The plant extracts were embedded in chitosan biopolymer particles and dispersed in a macromolecular chitosan solution. In addition, a two-layer coating, the first of a macromolecular chitosan solution, and the second of a dispersion of the embedded extracts in chitosan particles, was applied to the PLA films as a novel approach. The success of the coatings was monitored by X-ray photoelectron spectroscopy (XPS) and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), and the wettability was evaluated by contact angle measurements. Scanning electron microscopy SEM tracked the morphology and homogeneity of the coating. Antioxidation was studied by DPPH and ABTS spectrophotometric tests, and microbiological analysis of the films was performed according to the ISO 22196 Standard. Desorption of the coating from the PLA was monitored by reducing the elemental composition of the films themselves. The successful functionalization of PLA was demonstrated, while the XPS and ATR-FTIR analyses clearly showed the peaks of elemental composition of the extracts and chitosan on the PLA surface. Moreover, in all cases, the contact angle of the bilayer coatings decreased by more than 35–60% and contributed to the anti-fogging properties. The desorption experiments, due to decrease in the concentration of the specific typical element (nitrogen), indicated some migration of substances from the PLA’s surface. The newly developed films also exhibited antioxidant properties, with antioxidant ABTS efficiencies ranging from 83.5 to 100% and a quite high inhibition of Gram-positive Staphylococcus aureus bacteria, averaging over 95%. The current functionalization of PLA simultaneously confers antifogging, antioxidant, and antimicrobial properties and drives the development of a biodegradable and environmentally friendly composite material using green chemistry principles. Full article

Extrusion-based 3D bioprinting is a promising technique for fabricating multi-layered, complex biostructures, as it enables multi-material dispersion of bioinks with a straightforward procedure (particularly for users with limited additive manufacturing skills). Nonetheless, this method faces challenges in retaining the shape fidelity of the 3D-bioprinted structure, i.e., the collapse of filament (bioink) due to gravity and/or spreading of the bioink owing to the low viscosity, ultimately complicating the fabrication of multi-layered designs that can maintain the desired pore structure. While low viscosity is required to ensure a continuous flow of material (without clogging), a bioink should be viscous enough to retain its shape post-printing, highlighting the importance of bioink properties optimization. Here, two quantitative analyses are performed to evaluate shape fidelity. First, the filament collapse deformation is evaluated by printing different concentrations of alginate and its crosslinker (calcium chloride) by a co-axial nozzle over a platform to observe the overhanging deformation over time at two different ambient temperatures. In addition, a mathematical model is developed to estimate Young’s modulus and filament collapse over time. Second, the printability of alginate is improved by optimizing gelatin concentrations and analyzing the pore size area. In addition, the biocompatibility of proposed bioinks is evaluated with a cell viability test. The proposed bioink (3% w/v gelatin in 4% alginate) yielded a 98% normalized pore number (high shape fidelity) while maintaining >90% cell viability five days after being bioprinted. Integration of quantitative analysis/simulations and 3D printing facilitate the determination of the optimum composition and concentration of different elements of a bioink to prevent filament collapse or bioink spreading (post-printing), ultimately resulting in high shape fidelity (i.e., retaining the shape) and printing quality. Full article

Sulfate radicals (SO₄⁻·) play important biological roles in biomedical and environmental engineering, such as antimicrobial, antitumor, and disinfection. Compared with other common free radicals, it has the advantages of a longer half-life and higher oxidation potential, which could bring unexpected effects. These properties have prompted researchers to make great contributions to biology and environmental engineering by exploiting their properties. Peroxymonosulfate (PMS) and peroxydisulfate (PDS) are the main raw materials for SO₄⁻· formation. Due to the remarkable progress in nanotechnology, a large number of nanomaterials have been explored that can efficiently activate PMS/PDS, which have been used to generate SO₄⁻· for biological applications. Based on the superior properties and application potential of SO₄⁻·, it is of great significance to review its chemical mechanism, biological effect, and application field. Therefore, in this review, we summarize the latest design of nanomaterials that can effectually activate PMS/PDS to create SO₄⁻·, including metal-based nanomaterials, metal-free nanomaterials, and nanocomposites. Furthermore, we discuss the underlying mechanism of the activation of PMS/PDS using these nanomaterials and the application of SO₄⁻· in the fields of environmental remediation and biomedicine, liberating the application potential of SO₄⁻·. Finally, this review provides the existing problems and prospects of nanomaterials being used to generate SO₄⁻· in the future, providing new ideas and possibilities for the development of biomedicine and environmental remediation. Full article

Introduction: Chlorhexidine (CHX) has been used for some time in clinical practice as a local antiseptic agent with excellent efficacy. The combination of CHX with APRF (Advanced-platelet rich fibrin) membrane has the potential to stimulate tissue regeneration and to provide a bactericidal effect. We hypothesize that this may reduce the rate of infections development and protect cell viability. Aim: The aim of this study was two-fold—to create a stable APRF membrane treated with different concentrations of CHX (0.01% and 0.02%) and to monitor its effect on the viability of PDL cells in vitro. This benefits the introduction of a new protocol for APRF membrane production -CHX-PRF and enriches the available evidence on the effect of this antiseptic agent on PDL (Periodontal ligament) cells. Materials and methods: APRF membranes were prepared by the addition of two concentrations (0.01% and 0.02%) of CHX. Membranes without the antiseptic were also prepared and used as control samples. PDL cells were cultivated on the membranes for 72 h. Cell number and vitality were examined by fluorescent cell viability assays. Results: Our results demonstrated that a concentration of 0.01% CHX allowed the production of a stable APRF membrane. This concentration slightly reduced the viability of PDL cells to 96.7%, but significantly decreased the average number of cells attached to the membrane—149 ± 16.5 cells/field compared to controls −336 ± 26.9 cells/field. APRF-CHX 0.02% membranes were unstable, indicating a dose-dependent cytotoxic effect of CHX. Conclusions: The introduced novel protocol leads to the production of a new type of APRF membrane—CHX-PRF. The incorporation of an antiseptic into the APRF membrane can improve its bactericidal activity and might serve as an important step for the prevention of postoperative infections. Full article

Amino sugars N-acetylglucosamine (GlcNAc) and glucosamine (GlcN) are abundant sources of carbon and nitrogen in the oral cavity. The aim of this study was to investigate the effects of GlcNAc metabolism on the genomics and biochemistry of a saliva-derived microbial community, and on the surface integrity of human teeth and restorative surfaces. Pooled cell-containing saliva (CCS) was used to establish a microcosm biofilm in vitro in a biofilm medium (BM) containing 5 different carbohydrates. The microbial composition of each biofilm was analyzed by 16S rRNA amplicon sequencing, and the concentrations of eight organic acids were determined for selected sugars by targeted metabolomics. Meanwhile, extracted human teeth and polished titanium and ceramic disks were submerged in BM supplemented with 1% of glucose or GlcNAc, inoculated with CCS and Streptococcus mutans UA159, and incubated for 30 days. To mimic the effects of other microbial byproducts, the specimens were immersed in 10 mM hydrogen peroxide and 10 mM ammonium hydroxide for 30 days. The surface of each specimen was evaluated by profilometry for roughness (Ra) and imaged by scanning electron microscopy. The pH of the biofilm supernatant was significantly higher for the medium containing GlcNAc (p < 0.0001), and was higher in samples containing teeth than the two restorative disks for media containing the same sugar. For both teeth and titanium specimens, the samples treated with glucose-biofilm presented higher roughness values (Ra) than those with GlcNAc-biofilm and every other group. SEM images of the teeth and titanium disks largely supported the profilometry results, with glucose-biofilm samples demonstrating the largest deviation from the reference. For ceramic disks, slightly higher Ra values were obtained for the ammonia group. These findings provide the first direct evidence to support the ability of amino sugars to significantly reduce the cariogenic potential of oral biofilms by altering their biochemistry and bacterial composition. Additionally, amino sugar metabolism appears to be less detrimental to teeth and restorative surfaces than glucose metabolism. Full article

Magnesium has been extensively utilized to modify titanium implant surfaces based on its important function in promoting osteogenic differentiation. Autophagy has been proven to play a vital role in bone metabolism. Whether there is an association between autophagy and magnesium in promoting osteogenic differentiation remains unclear. In the present study, we focused on investigating the role of magnesium ions in early osteogenic activity and the underlying mechanism related to autophagy. Different concentrations of magnesium were embedded in micro-structured titanium surface layers using the micro-arc oxidation (MAO) technique. The incorporation of magnesium benefited cell adhesion, spreading, and viability; attenuated intracellular ATP concentrations and p-mTOR levels; and upregulated p-AMPK levels. This indicates the vital role of the ATP-related AMPK/mTOR signaling pathway in the autophagy process associated with osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) induced by magnesium modification on titanium surfaces. The enhanced osteogenic differentiation and improved cellular autophagy activity of BMSCs in their extraction medium further confirmed the function of magnesium ions. The results of the present study advance our understanding of the mechanism by which magnesium regulates BMSC osteogenic differentiation through autophagy regulation. Moreover, endowing implants with the ability to activate autophagy may be a promising strategy for enhancing osseointegration in the translational medicine field in the future. Full article

Among the urinary tract’s malignancies, bladder cancer is the most frequent one: it is at the tenth position of most common cancers worldwide. Currently, the gold standard therapy consists of radical cystectomy, which results in the need to create a urinary diversion using a bowel segment from the patient. Nevertheless, due to several complications associated with bowel resection and anastomosis, which significantly affect patient quality of life, it is becoming extremely important to find an alternative solution. In our recent work, we proposed the decellularized porcine small intestinal submucosa (SIS) as a candidate material for urinary conduit substitution. In the present study, we create SIS-based hybrid membranes that are obtained by coupling decellularized SIS with two commercially available polycarbonate urethanes (Chronoflex AR and Chronoflex AR-LT) to improve SIS mechanical resistance and impermeability. We evaluated the hybrid membranes by means of immunofluorescence, two-photon microscopy, FTIR analysis, and mechanical and cytocompatibility tests. The realization of hybrid membranes did not deteriorate SIS composition, but the presence of polymers ameliorates the mechanical behavior of the hybrid constructs. Moreover, the cytocompatibility tests demonstrated a significant increase in cell growth compared to decellularized SIS alone. In light of the present results, the hybrid membrane-based urinary conduit can be a suitable candidate to realize a urinary diversion in place of an autologous intestinal segment. Further efforts will be performed in order to create a cylindrical-shaped hybrid membrane and to study its hydraulic behavior. Full article

Numerous studies have been reported on single- and multicolored highly fluorescent carbon nanoparticles (FCNPs) originating from various sources and their potential applications in bioimaging. Herein, multicolored biocompatible carbon nanoparticles (CNPs) unsheathed from date palm fronds were studied. The extracted CNPs were characterized via several microscopic and spectroscopic techniques. The results revealed that the CNPs were crystalline graphitic and hydrophilic in nature with sizes ranging from 4 to 20 nm. The unsheathed CNPs showed exemplary photoluminescent (PL) properties. They also emitted bright blue colors when exposed to ultraviolet (UV) light. Furthermore, in vitro cellular uptake and cell viability in the presence of CNPs were also investigated. The cell viability of human colon cancer (HCT-116) and breast adenocarcinoma (MCF-7) cell lines with aqueous CNPs at different concentrations was assessed by a cell metabolic activity assay (MTT) for 24 and 48 h incubations. The results were combined to generate dose-response curves for the CNPs and evaluate the severity of their toxicity. The CNPs showed adequate fluorescence with high cell viability for in vitro cell imaging. Under the laser-scanning confocal microscope, the CNPs with HCT-116 and MCF-7 cell lines showed multicolor fluorescence emissions, including blue, green, and red colors when excited at 405, 458, and 561 nm, respectively. These results prove that unsheathed CNPs from date palm fronds can be used in diverse biomedical applications because of their low cytotoxicity, adequate fluorescence, eco-friendly nature, and cheap production. Full article

Bacterial infections pose a serious threat to people’s health. Efforts are being made to develop antibacterial agents that can inhibit bacterial growth, prevent biofilm formation, and kill bacteria. In recent years, materials based on metal organic frameworks (MOFs) have attracted significant attention for various antibacterial applications due to their high specific surface area, high enzyme-like activity, and continuous release of metal ions. This paper reviews the recent progress of MOFs as antibacterial agents, focusing on preparation methods, fundamental antibacterial mechanisms, and strategies to enhance their antibacterial effects. Finally, several prospects related to MOFs for antibacterial application are proposed, aiming to provide possible research directions in this field. Full article

Adsorbents for whole blood apheresis need to be highly blood compatible to minimize the activation of blood cells on the biomaterial surface. Here, we developed blood-compatible matrices by surface modification with polyzwitterionic polysulfobetainic and polycarboxybetainic coatings. Photoreactive zwitterionic terpolymers were synthesized by free-radical polymerization of zwitterionic, photoreactive, and fluorescent monomers. Upon UV irradiation, the terpolymers were photodeposited and mutually crosslinked on the surface of hydrophobic polystyrene-co-divinylbenzene and hydrophilic polyacrylamide-co-polyacrylate (DALI) beads. Fluorescent microscopy revealed coatings with an average thickness of 5 µm, which were limited to the bead surface. Blood compatibility was assessed based on polymer-induced hemolysis, coagulation parameters, and in vitro tests. The maintenance of the adsorption capacity after coating was studied in human whole blood with cytokines for polystyrene beads (remained capacity 25–67%) and with low-density lipoprotein (remained capacity 80%) for polyacrylate beads. Coating enhanced the blood compatibility of hydrophobic, but not of hydrophilic adsorbents. The most prominent effect was observed on coagulation parameters (e.g., PT, aPTT, TT, and protein C) and neutrophil count. Polycarboxybetaine with a charge spacer of five carbons was the most promising polyzwitterion for the coating of adsorbents for whole blood apheresis. Full article

Wire arc additive manufacturing (WAAM) offers a high rate of material deposition among various additive manufacturing techniques with wire as feedstock material but has not been established for zinc alloys. Zn alloys can be used as degradable biomaterials, in contrast to conventional permanent metallic biomaterials. In this work, commercially pure Zn was processed by WAAM to obtain near-dense parts, and the properties obtained through WAAM-processed Zn were compared with wrought (WR) Zn samples. The microstructure and hardness values of the WAAM (41 ± 1 HV0.3) components were found to be similar to those of the WR (35 ± 2 HV0.3) components. Bulk X-ray diffraction texture measurements suggested that WAAM builds exhibit a heavily textured microstructure compared to the WR counterparts, with peak intensities around <3 3–6 2> or <0 0 0 2> in the directions parallel to the build direction (BD). The corrosion rates in simulated body fluid (SBF) were similar for WAAM (0.45 mmpy) and WR (0.3 mmpy) samples. The weight loss measurements in SBF were found to be marginally higher in the WAAM samples compared to the WR counterparts for a duration of up to 21 days. MC3T3-E1 preosteoblasts were found to be healthy and proliferating in the culture medium containing the degradation products from WAAM-Zn in a manner similar to WR-Zn. This work establishes the feasibility of processing Zn by WAAM for use in bioresorbable metallic implants. Full article

Objective: Researchers are studying the use of antimicrobial peptides as functional biomaterials to prevent and treat dental caries. This study aims to investigate the global research interest in antimicrobial peptides for caries management. Methods: Two independent investigators systematically searched with keywords (‘Caries’ OR ‘Dental caries’) AND (‘Antimicrobial peptide’ OR ‘AMP’ OR ‘Statherin’ OR ‘Histatin’ OR ‘Defensin’ OR ‘Cathelicidin’) on Web of Science, PubMed and Scopus. They removed duplicate publications and screened the titles and abstracts to identify relevant publications. The included publications were summarized and classified as laboratory studies, clinical trials or reviews. The citation count and citation density of the three publication types were compared using a one-way analysis of variance. The publications’ bibliometric data were analyzed using the Bibliometrix program. Results: This study included 163 publications with 115 laboratory studies (71%), 29 clinical trials (18%) and 19 reviews (11%). The number of publications per year have increased steadily since 2002. The citation densities (mean ± SD) of laboratory study publications (3.67 ± 2.73) and clinical trial publications (2.63 ± 1.85) were less than that of review articles (5.79 ± 1.27) (p = 0.002). The three publication types had no significant difference in citation count (p = 0.54). Most publications (79%, 129/163) reported the development of a novel antimicrobial peptide. China (52/163, 32%) and the US (29/163, 18%) contributed to 50% (81/163) of the publications. Conclusion: This bibliometric analysis identified an increasing trend in global interest in antimicrobial peptides for caries management since 2002. The main research topic was the development of novel antimicrobial peptides. Most publications were laboratory studies, as were the three publications with the highest citation counts. Laboratory studies had high citation counts, whereas reviews had high citation density. Full article

After the elimination of dental caries lesions, some microorganisms may remain viable in the tooth structure. Thus, cavity disinfection is an important procedure. The aim of this study was to evaluate the effect of cavity disinfectants on the adhesion to dentin of permanent teeth. Sixty molars were ground flat and randomly assigned to six groups: control; chlorhexidine; Aloe vera; glutaraldehyde; EDTA; ethanol. Cavity disinfectants were applied, rinsed, and air-dried. The restorations were performed with the aid of polyethylene tubes. Shear bond strength, work to detachment, and shear modulus were evaluated. All data were statistically analyzed and the level of significance was set at 5%. The control group showed the lowest shear bond strength (8.34 ± 2.68 MPa). Aloe vera showed the lowest work to debonding (2284 J/m²) while chlorhexidine showed the highest (9347 J/m²). Regarding the shear modulus, ethanol, chlorhexidine, and EDTA presented similar values to the control group (216.11 kPa), and glutaraldehyde and Aloe vera presented values twice as high. The use of chlorhexidine, ethanol, EDTA, glutaraldehyde, and Aloe vera did not impair the adhesion established between the dentin of permanent teeth and composite resin. Even though there is a need for clinical studies to support these findings, all disinfectants seem to be good choices as pretreatment agents. Full article

Background: Although the influence of titanium implants’ micro-surface properties on titanium discs has been extensively investigated, the research has not taken into consideration their whole-body effect, which may be considered possible using a combinatorial approach. Methods: Five titanium dental implants with a similar moderate roughness and different surface textures were thoroughly characterized. The cell adhesion and proliferation were assessed after adipose-tissue-derived stem cells (ADSCs) were seeded on whole-body implants. The implants’ inductive properties were assessed by evaluating the osteoblastic gene expression. Results: The surface micro-topography was analyzed, showing that hydroxyapatite (HA)-blasted and bland acid etching implants had the highest roughness and a lower number of surface particles. Cell adhesion was observed after 24 h on all the implants, with the highest score registered for the HA-blasted and bland acid etching implants. Cell proliferation was observed only on the laser-treated and double-acid-etched surfaces. The ADSCs expressed collagen type I, osteonectin, and alkaline phosphatase on all the implant surfaces, with high levels on the HA-treated surfaces, which also triggered osteocalcin expression on day seven. Conclusions: The findings of this study show that the morphology and treatment of whole titanium dental implants, primarily HA-treated and bland acid etching implants, impact the adherence and activity of ADSCs in osteogenic differentiation in the absence of specific osteo-inductive signals. Full article

The main objective of the proposed work was the development of a thermosensitive gel (containing clove and tea tree oil) for the management of vaginal candidiasis. Both oils have been recommended to be used separately in a topical formulation for vaginal candidiasis. Incorporating two natural ingredients (clove and tea tree oil) into a product give it a broad antimicrobial spectrum and analgesic properties. The two oils were mixed together at a 3:1 ratio and converted into o/w nanoemulsion using the aqueous titration method and plotting pseudo ternary phase diagrams. Further transformations resulted in a gel with thermosensitive properties. To determine the final formulation’s potential for further clinical investigation, in vitro analyses (viscosity measurement, MTT assay, mucoadhesion, ex vivo permeation) and in vivo studies (fungal clearance kinetics in an animal model) were conducted. The current effort leveraged the potential of tea tree and clove oils as formulation ingredients and natural therapeutic agents for vaginal infections. Its synergy generated a stable and effective thermosensitive gel that can be utilized for recurrent candidiasis and other infections. Full article