Editor’s Choice Articles

The development of antimicrobial devices and surfaces requires the setup of suitable materials, able to store and release active principles. In this context, zeolites, which are microporous aluminosilicate minerals, hold great promise, since they are able to serve as a reservoir for metal-ions with antimicrobial properties. Here, we report on the preparation of Linde Type A zeolites, partially exchanged with combinations of metal-ions (Ag⁺, Cu²⁺, Zn²⁺) at different loadings (0.1–11.9 wt.%). We combine X-ray fluorescence, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray diffraction to monitor the metal-ion contents, distribution, and conservation of the zeolite structure after exchange. Then, we evaluate their antimicrobial activity, using agar dilution and optical-density monitoring of Escherichia coli cultures. The results indicate that silver-loaded materials are at least 70-fold more active than the copper-, zinc-, and non-exchanged ones. Moreover, zeolites loaded with lower Ag⁺ concentrations remain active down to 0.1 wt.%, and their activities are directly proportional to the total Ag content. Sequential exchanges with two metal ions (Ag⁺ and either Cu²⁺, Zn²⁺) display synergetic or antagonist effects, depending on the quantity of the second metal. Altogether, this work shows that, by combining analytical and quantitative methods, it is possible to fine-tune the composition of bi-metal-exchanged zeolites, in order to maximise their antimicrobial potential, opening new ways for the development of next-generation composite zeolite-containing antimicrobial materials, with potential applications for the design of dental or bone implants, as well as biomedical devices and pharmaceutical products. Full article

Biodegradable metals have been extensively studied due to their potential use as temporary biomedical devices, on non-load bearing applications. These types of implants are requested to function for the healing period, and should degrade after the tissue heals. A balance between mechanical properties requested at the initial stage of implantation and the degradation rate is required. The use of temporary biodegradable implants avoids a second surgery for the removal of the device, which brings high benefits to the patients and avoids high societal costs. Among the biodegradable metals, iron as a biodegradable metal has increased attention over the last few years, especially with the incorporation of additive manufacturing processes to obtain tailored geometries of porous structures, which give rise to higher corrosion rates. Withal by mimic natural bone hierarchical porosity, the mechanical properties of obtained structures tend to equalize that of human bone. This review article presents some of the most important works in the field of iron and porous iron. Fabrication techniques for porous iron are tackled, including conventional and new methods highlighting the unparalleled opportunities given by additive manufacturing. A comparison among the several methods is taken. The effects of the design and the alloying elements on the mechanical properties are also revised. Iron alloys with antibacterial properties are analyzed, as well as the biodegradation behavior and biocompatibility of iron. Although is necessary for further in vivo research, iron is presenting satisfactory results for upcoming biomedical applications, as orthopaedic temporary scaffolds and coronary stents. Full article

The combination of titania nanofilms and silver nanoparticles (NPs) is a very promising material, with antibacterial and osseointegration-induced properties for titanium implant coatings. In this work, we successfully prepared TiO₂ nanolayer/Ag NP structures on titanium disks using atomic layer deposition (ALD). The samples were studied by scanning electron microscopy (SEM), X-ray diffraction, X-ray photoelectron spectroscopy (XPS), contact angle measurements, and SEM-EDS. Antibacterial activity was tested against Staphylococcus aureus. The in vitro cytological response of MG-63 osteosarcoma and human fetal mesenchymal stem cells (FetMSCs) was examined using SEM study of their morphology, MTT test of viability and differentiation using alkaline phosphatase and osteopontin with and without medium-induced differentiation in the osteogenic direction. The samples with TiO₂ nanolayers, Ag NPs, and a TiO₂/Ag combination showed high antibacterial activity, differentiation in the osteogenic direction, and non-cytotoxicity. The medium for differentiation significantly improved osteogenic differentiation, but the ALD coatings also stimulated differentiation in the absence of the medium. The TiO₂/Ag samples showed the best antibacterial ability and differentiation in the osteogenic direction, indicating the success of the combining of TiO₂ and Ag to produce a multifunctional biocompatible and bactericidal material. Full article

Peripheral nerve injury (PNI) is a neurological disorder that causes more than 9 million patients to suffer from dysfunction of moving and sensing. Using biodegradable polymers to fabricate an artificial nerve conduit that replicates the environment of the extracellular matrix and guides neuron regeneration through the damaged sites has been researched for decades and has led to promising but primarily pre-clinical outcomes. However, few peripheral nerve conduits (PNCs) have been constructed from controllable biodegradable polymeric materials that can maintain their structural integrity or completely degrade during and after nerve regeneration respectively. In this work, a novel PNC candidate material was developed via the electrospinning of polyhydroxy butyrate/chitosan (PHB/CS) composite polymers. An SEM characterisation revealed the resultant PHB/CS nanofibres with 0, 1 and 2 wt/v% CS had less and smaller beads than the nanofibres at 3 wt/v% CS. The water contact angle (WCA) measurement demonstrated that the wettability of PHB/CS electrospun fibres was significantly improved by additional CS. Furthermore, both the thermogravimetric analysis (TGA) and differentiation scanning calorimetry (DSC) results showed that PHB/CS polymers can be blended in a single phase with a trifluoracetic solvent in all compositions. Besides, the reduction in the degradation temperature (from 286.9 to 229.9 °C) and crystallinity (from 81.0% to 52.1%) with increasing contents of CS were further proven. Moreover, we found that the degradability of the PHB/CS nanofibres subjected to different pH values rated in the order of acidic > alkaline > phosphate buffer solution (PBS). Based on these findings, it can be concluded that PHB/CS electrospun fibres with variable blending ratios may be used for designing PNCs with controlled biodegradability. Full article

Mineralized collagen is the basic unit in hierarchically organized natural bone with different structures. Polyacrylic acid (PAA) and periodic fluid shear stress (FSS) are the most common chemical and physical means to induce intrafibrillar mineralization. In the present study, non-mineralized collagen, extrafibrillar mineralized (EM) collagen, intrafibrillar mineralized (IM) collagen, and hierarchical intrafibrillar mineralized (HIM) collagen induced by PAA and FSS were prepared, respectively. The physical and chemical properties of these mineralized collagens with different microstructures were systematically investigated afterwards. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) showed that mineralized collagen with different microstructures was prepared successfully. The pore density of the mineralized collagen scaffold is higher under the action of periodic FSS. Fourier transform infrared spectroscopy (FTIR) analysis showed the formation of the hydroxyapatite (HA) crystal. A significant improvement in the pore density, hydrophilicity, enzymatic stability, and thermal stability of the mineralized collagen indicated that the IM collagen under the action of periodic FSS was beneficial for maintaining collagen activity. HIM collagen fibers, which are prepared under the co-action of periodic FSS and sodium tripolyphosphate (TPP), may pave the way for new bone substitute material applications. Full article

Herein, a nanocomposite hydrogel was produced using laponite and polyethylene-glycol diacrylate (PEGDA), with or without Irgacure (IG), for application in bone tissue regeneration. The nanocomposites were characterized by X-ray diffraction (XRD), Fourier-Transform infrared spectroscopy (FTIR), and thermal analysis (TG/DTG). The XRD results showed that the crystallographic structure of laponite was preserved in the nanocomposite hydrogels after the incorporation of PEGDA and IG. The FTIR results indicated that PEGDA polymer chains were entangled on laponite in hydrogels. The TG/DTG found that the presence of laponite (Lap) improved the thermal stability of nanocomposite hydrogel. The toxicity tests by Artemia salina indicated that the nanocomposite hydrogels were not toxic, because the amount of live nauplii was 80.0%. In addition, in vivo tests demonstrated that the hydrogels had the ability to regenerate bone in a bone defect model of the tibiae of osteopenic rats. For the nanocomposite hydrogel (PEGDA + Lap nanocomposites + UV light), the formation of intramembranous bone in the soft callus was more intense in 66.7% of the animals. Thus, the results presented in this study evidence that nanocomposite hydrogels obtained from laponite and PEGDA have the potential for use in bone regeneration. Full article

The quest for an ideal biomaterial perfectly matching the microenvironment of the surrounding tissues and cells is an endless challenge within biomedical research, in addition to integrating this with a facile and sustainable technology for its preparation. Engineering hydrogels through click chemistry would promote the sustainable invention of tailor-made hydrogels. Herein, we disclose a versatile and facile catalyst-free click chemistry for the generation of an innovative hydrogel by combining chondroitin sulfate (CS) and polyethylene glycol (PEG). Various multi-armed PEG-Norbornene (A-PEG-N) with different molecular sizes were investigated to generate crosslinked copolymers with tunable rheological and mechanical properties. The crosslinked and mechanically stable porous hydrogels could be generated by simply mixing the two clickable Tetrazine-CS (TCS) and A-PEG-N components, generating a self-standing hydrogel within minutes. The leading candidate (TCS-8A-PEG-N (40 kD)), based on the mechanical and biocompatibility results, was further employed as a scaffold to improve wound closure and blood flow in vivo. The hydrogel demonstrated not only enhanced blood perfusion and an increased number of blood vessels, but also desirable fibrous matrix orientation and normal collagen deposition. Taken together, these results demonstrate the potential of the hydrogel to improve wound repair and hold promise for in situ skin tissue engineering applications. Full article

Titanium implants are frequently applied to the bone in orthopedic and trauma surgery. Although these biomaterials are characterized by excellent implant survivorship and clinical outcomes, there are almost no data available on the initial protein layer binding to the implant surface in situ. This study aims to investigate the composition of the initial protein layer on endoprosthetic surfaces as a key initiating step in osseointegration. In patients qualified for total hip arthroplasty, the implants are inserted into the femoral canal, fixed and subsequently explanted after 2 and 5 min. The proteins adsorbed to the surface (the implant proteome) are analyzed by liquid chromatography–tandem mass spectrometry (LC-MS/MS). A statistical analysis of the proteins’ alteration with longer incubation times reveals a slight change in their abundance according to the Vroman effect. The pathways involved in the extracellular matrix organization of bone, sterile inflammation and the beginning of an immunogenic response governed by neutrophils are significantly enriched based on the analysis of the implant proteome. Those are generally not changed with longer incubation times. In summary, proteins relevant for osseointegration are already adsorbed within 2 min in situ. A deeper understanding of the in situ protein–implant interactions in patients may contribute to optimizing implant surfaces in orthopedic and trauma surgery. Full article

Due to their superior mechanical and chemical properties, titanium (Ti) and its alloys have been widely used as orthopedic implantable devices. However, their bioinertness represents a limitation, which can be overcome by employing various surface modifications, such as TiO₂ nanotube (TNT) fabrication via electrochemical anodization. Anodic TNTs present tunable dimensions and unique structures, turning them into feasible drug delivery platforms. In the present work, TNTs were loaded with icariin (Ica) through an adhesive intermediate layer of polydopamine (DP), and their in vitro and in vivo biological performance was evaluated. The successful fabrication of the modified surfaces was verified by scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), and contact angle measurements (CA), while the in vitro release of Ica was evaluated via UV-VIS spectrophotometry. In terms of in vitro behaviour, comparative studies on RAW 264.7 macrophages demonstrated that the TNT substrates, especially TNT-DP-Ica, elicited a lower inflammatory response compared to the Ti support. Moreover, the in vivo implantation studies evinced generation of a reduced fibrotic capsule around this implant and increased thickness of the newly formed bone tissue at 1 month and 3 months post-implantation, respectively. Overall, our results indicate that the controlled release of Ica from TNT surfaces could result in an improved osseointegration process. Full article

Modern structural materials are represented by a variety of polymer materials used for dental patients’ rehabilitation. They differ not only in physico-chemical properties, but also in microbiological properties, which is one of the reasons why these materials are chosen. The study focused on the microbial adhesion of clinical isolates of normal (5 types), periodontopathogenic (2 types), and fungal (2 types) microbiotas to various materials based on polymethylmethacrylate (PMMA) intended for traditional (cold-cured and hot-cured polymers), computer-aided subtractive and additive manufacturing. A comparative analysis was carried out on the studied samples of polymer materials according to the microorganisms’ adhesion index (AI). The lowest level of microorganisms’ AI of the three types of microbiotas was determined in relation to materials for additive manufacturing. The AI of hot-cured polymers, as well as materials for subtractive manufacturing, corresponded to the average level. The highest level of microorganisms’ adhesion was found in cold-cured polymers. Significant differences in AI for materials of the same technological production type (different manufacturers) were also determined. The tendency of significant differences in the indicators of the microorganisms’ adhesion level for the studied polymer materials on the basis of the type of production technology was determined. Full article

Extrusion bioprinting is an emerging technology to apply biomaterials precisely with living cells (referred to as bioink) layer by layer to create three-dimensional (3D) functional constructs for tissue engineering. Printability and cell viability are two critical issues in the extrusion bioprinting process; printability refers to the capacity to form and maintain reproducible 3D structure and cell viability characterizes the amount or percentage of survival cells during printing. Research reveals that both printability and cell viability can be affected by various parameters associated with the construct design, bioinks, and bioprinting process. This paper briefly reviews the literature with the aim to identify the affecting parameters and highlight the methods or strategies for rigorously determining or optimizing them for improved printability and cell viability. This paper presents the review and discussion mainly from experimental, computational, and machine learning (ML) views, given their promising in this field. It is envisioned that ML will be a powerful tool to advance bioprinting for tissue engineering. Full article

Epigenetic approaches using the histone deacetylase 2 and 3 inhibitor-MI192 have been reported to accelerate stem cells to form mineralised tissues. Gelatine methacryloyl (GelMA) hydrogels provide a favourable microenvironment to facilitate cell delivery and support tissue formation. However, their application for bone repair is limited due to their low mechanical strength. This study aimed to investigate a GelMA hydrogel reinforced with a 3D printed scaffold to support MI192-induced human bone marrow stromal cells (hBMSCs) for bone formation. Cell culture: The GelMA (5 wt%) hydrogel supported the proliferation of MI192-pre-treated hBMSCs. MI192-pre-treated hBMSCs within the GelMA in osteogenic culture significantly increased alkaline phosphatase activity (p ≤ 0.001) compared to control. Histology: The MI192-pre-treated group enhanced osteoblast-related extracellular matrix deposition and mineralisation (p ≤ 0.001) compared to control. Mechanical testing: GelMA hydrogels reinforced with 3D printed poly(ethylene glycol)-terephthalate/poly(butylene terephthalate) (PEGT/PBT) scaffolds exhibited a 1000-fold increase in the compressive modulus compared to the GelMA alone. MI192-pre-treated hBMSCs within the GelMA–PEGT/PBT constructs significantly enhanced extracellular matrix collagen production and mineralisation compared to control (p ≤ 0.001). These findings demonstrate that the GelMA–PEGT/PBT construct provides enhanced mechanical strength and facilitates the delivery of epigenetically-activated MSCs for bone augmentation strategies. Full article

Achieving homogenous dispersion of nanoparticles inside a polymeric matrix is a great challenge for numerous applications. In the present study, we aim at understanding the role of different factors on the dispersion properties of TiO₂ in pluronic F-127 mixtures. The mixtures were prepared with different pH and guest/host ratios and investigated by UV-Vis spectroscopy, dynamic light scattering, infrared spectroscopy and electrical conductivity. Depending on the preparation conditions, different amounts of TiO₂ were loaded within the copolymer as quantitatively determined by UV-Vis spectroscopy. The different content of nanoparticles has direct implications on the gelation and micellization of pluronic analyzed by dynamic light scattering. The information derived on the self-assembly behavior was interpreted in relation to the infrared and conductivity measurements results. Together, these results shed light on the most favorable conditions for improving the nanoparticle dispersion inside the copolymer matrix and suggest a possible strategy to design functional nanoparticle-polymer systems. Full article

The aim of this paper is to systematically analyse the effect of calcium silicate-based sealers in comparison to resin-based sealers on clinical and radiographic outcomes of non-surgical endodontic treatment in permanent teeth. Methods: The study was conducted according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. The literature search was performed using PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, DOAJ and OpenGrey with no language restrictions. Two reviewers critically assessed the studies for eligibility. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was carried out to assess the evidence. Meta-analysis of the pooled data with subgroups was carried out using the RevMan software (p < 0.05). Results: Results from the included studies showed that there were no significant differences between the groups in the 24 h post-obturation pain levels (mean difference (MD), −0.19, 95% CI = −0.43–0.06, p = 0.14, I² = 0%), but at 48 h (MD, −0.35, 95% CI = −0.64–0.05, p = 0.02, I² = 0%), a significant difference was observed in favour of calcium silicate sealers. Furthermore, there were no significant differences between the two sealers due to risk of onset or intensity of postoperative pain, need for analgesic and extrusion of the sealer. The heterogeneity assessed using Q test between the included studies was 97% (I²). Conclusions: Within the limitations of this review, the paper shows that calcium silicate-based sealers exhibited optimal performance with similar results to resin-based sealers in terms of average level of post-obturation pain, risk of onset and pain intensity at 24 and 48 h. The observations from the included studies are informative in the clinical evaluation of calcium silicate-based sealers and provide evidence for the conduction of well-designed, controlled randomised clinical trials for a period of at least four years in the future. Full article

Lysosomal storage disorders (LSDs) are a set of metabolic diseases caused by mutations in genes that are in charge of the production of lysosomal enzymes, resulting in the buildup of non-degraded substrates and the consequent systemic damage that mainly involves the Central Nervous System (CNS). One of the most widely used and studied treatments is Enzyme Replacement Therapy, which is based on the administration of the recombinant deficient enzyme. This strategy has often proved fallacious due to the enzyme instability in body fluids and its inability to reach adequate levels in the CNS. In this work, we developed a system based on nanotechnology that allows a stable enzyme to be obtained by its covalent immobilization on nanoparticles (NPs) of polylactic acid, subsequently administered to a cellular model of LSDs, i.e., Sandhoff disease, caused by the absence or deficiency of the β-d-N-acetyl-hexosaminidase A (HexA) enzyme. The HexA enzymes, loaded onto the polymeric NPs through an immobilization procedure that has already been investigated and validated, were found to be stable over time, maintain optimal kinetic parameters, be able to permeate the plasma membrane, hydrolyze HexA’s natural substrate, and restore enzyme activity close to the levels of healthy cells. These results thus lay the foundation for testing the HexA-NPs in animal models of the disease and thus obtaining an efficient drug-delivery system. Full article

Neutralising monoclonal antibodies for tumour necrosis factor (TNF) has been widely used to treat Crohn’s disease (CD) in clinical practice. However, differential individual response necessitates a therapeutic response assessment of anti-TNF agents in CD patients for optimizing therapeutic strategy. We aimed to predict anti-TNF therapy response in CD patients using transcriptome analyses. Transcriptome analyses were performed using data from the Gene Expression Omnibus, GeneCards, and Human Protein Atlas databases. The significantly mitigated biological functions associated with anti-TNF therapy resistance in CD patients encompassed immune pathways, including Interleukin-17 (IL-17) signaling, cytokine-cytokine receptor interaction, and rheumatoid arthritis. The scores of immune cell markers, including neutrophils, monocytes, and macrophages/monocytes were also significantly decreased in non-responders compared with that measured in anti-TNF therapy responders. The KAT2B gene, associated with IL-17 cytokine mediated neutrophil mobilization and activation, was significantly under-expressed in both tissue and peripheral blood mononuclear cells (PBMCs) in anti-TNF therapy-resistant CD patients. The reduced expression of several pro-inflammatory cytokines due to down-regulated IL-17 signaling, is suggestive of the primary non-response to anti-TNF agents in CD patients. Furthermore, the PBMC KAT2B gene signature may be a promising pre-treatment prognostic biomarker for anti-TNF drug response in CD patients. Full article

Orthopedic and craniofacial surgical procedures require the reconstruction of bone defects caused by trauma, diseases, and tumor resection. Successful bone restoration entails the development and use of bone grafts with structural, functional, and biological features similar to native tissues. Herein, we developed three-dimensional (3D) printed fine-tuned hydroxyapatite (HA) biomimetic bone structures, which can be applied as grafts, by using calcium phosphate cement (CPC) bioink, which is composed of tetracalcium phosphate (TTCP), dicalcium phosphate anhydrous (DCPA), and a liquid [Polyvinyl butyral (PVB) dissolved in ethanol (EtOH)]. The ink was ejected through a high-resolution syringe nozzle (210 µm) at room temperature into three different concentrations (0.01, 0.1, and 0.5) mol/L of the aqueous sodium phosphate dibasic (Na₂HPO₄) bath that serves as a hardening accelerator for HA formation. Raman spectrometer, X-ray diffraction (XRD), and scanning electron microscopy (SEM) demonstrated the real-time HA formation in (0.01, 0.1, and 0.5) mol/L Na₂HPO₄ baths. Under those conditions_, HA was formed at different amounts, which tuned the scaffolds’ mechanical properties, porosity, and osteoclast activity. Overall, this method may pave the way to engineer 3D bone scaffolds with controlled HA composition and pre-defined properties, which will enhance graft-host integration in various anatomic locations. Full article

Zinc oxide nanoparticles (ZnONPs) are inorganic nano-biomaterials with excellent antimicrobial properties. However, their effects on the anti-infection ability of the innate immune system remains poorly understood. The aim of the present study was to explore the potential immunomodulatory effects of ZnONPs on the innate immune system, represented by polymorphonuclear leukocytes (PMNs), and determine whether they can act synergistically to resist pathogen infections. In vitro experiment showed that ZnONPs not only exhibit obvious antibacterial activity at biocompatible concentrations but also enhance the antibacterial property of PMNs. In vivo experiments demonstrated the antibacterial effect of ZnONPs, accompanied by more infiltration of subcutaneous immune cells. Further ex vivo and in vitro experiments revealed that ZnONPs enhanced the migration of PMNs, promoted their bacterial phagocytosis efficiency, proinflammatory cytokine (TNF-α, IL-1β, and IL-6) expression, and reactive oxygen species (ROS) production. In summary, this study revealed potential synergistic effects of ZnONPs on PMNs to resist pathogen infection and the underlying mechanisms. The findings suggest that attempts should be made to fabricate and apply biomaterials in order to maximize their synergy with the innate immune system, thus promoting the host’s resistance to pathogen invasion. Full article

Poly(methyl methacrylate) (PMMA)-based resins have been conventionally used in dental prostheses owing to their good biocompatibility. However, PMMA-based resins have relatively poor mechanical properties. In the present study, a novel nanoporous silica filler was developed and introduced into PMMA-based resins to improve their mechanical properties. The filler was prepared by sintering a green body composed of silica and an organic binder, followed by grinding to a fine powder and subsequent silanization. The filler was added to photocurable PMMA-based resin, which was prepared from MMA, PMMA, ethylene glycol dimethacrylate, and a photo-initiator. The filler was characterized by scanning electron microscopy (SEM), X-ray diffraction analysis, nitrogen sorption porosimetry, and Fourier transform infrared (FT-IR) spectroscopy. The PMMA-based resins were characterized by SEM and FT-IR, and the mechanical properties (Vickers hardness, flexural modulus, and flexural strength) and physicochemical properties (water sorption and solubility) were evaluated. The results suggested that the filler consisted of microparticles with nanopores. The filler at 23 wt % was well dispersed in the PMMA-based resin matrix. The mechanical and physicochemical properties of the PMMA-based resin improved significantly with the addition of the developed filler. Therefore, such filler-loaded PMMA-based resins are potential candidates for improving the strength and durability of polymer-based crown and denture base. Full article

Physical features on the biomaterial surface are known to affect macrophage cell shape and phenotype, providing opportunities for the design of novel “immune-instructive” topographies to modulate foreign body response. The work presented here employed nanopatterned polydimethylsiloxane substrates with well-characterized nanopillars and nanopits to assess RAW264.7 macrophage response to feature size. Macrophages responded to the small nanopillars (SNPLs) substrates (450 nm in diameter with average 300 nm edge-edge spacing), resulting in larger and well-spread cell morphology. Increasing interpillar distance to 800 nm in the large nanopillars (LNPLs) led to macrophages exhibiting morphologies similar to being cultured on the flat control. Macrophages responded to the nanopits (NPTs with 150 nm deep and average 800 nm edge-edge spacing) by a significant increase in cell elongation. Elongation and well-spread cell shape led to expression of anti-inflammatory/pro-healing (M2) phenotypic markers and downregulated expression of inflammatory cytokines. SNPLs and NPTs with high availability of integrin binding region of fibronectin facilitated integrin β1 expression and thus stored focal adhesion formation. Increased integrin β1 expression in macrophages on the SNPLs and NTPs was required for activation of the PI3K/Akt pathway, which promoted macrophage cell spreading and negatively regulated NF-κB activation as evidenced by similar globular cell shape and higher level of NF-κB expression after PI3K blockade. These observations suggested that alterations in macrophage cell shape from surface nanotopographies may provide vital cues to orchestrate macrophage phenotype. Full article

The laser micro-machining was carried out on a station equipped with a TruMicro 5325c laser emitting ultraviolet radiation (343 nm wavelength) in picosecond pulses. On the surface of the Ti6Al7Nb alloy, dimple texturing with a constant diameter of ~200 μm, different depths (from ~5 to ~78 μm) and density (from 10% to 50%) were produced. The value of surface free energy was determined with the Owens–Wendt method using two measuring liquids: distilled water and diodomethane. The Staphylococcus epidermidis strain was used to test the adhesion of bacteria. It was found that the surface free energy value is influenced by both of the texture parameters (density, depth). The density also affects the potential for biofilm formation. Based on the analysis, it was shown that with an increase in surface free energy, the number of adhering microorganisms increases exponentially. Moreover, the study shows that there is a correlation between the number of adhering microorganisms and surface free energy. Full article

Antibacterial coating with antibiotics is highly effective in avoiding device-associated infections (DAIs) which is an unsolved healthcare problem that causes significant morbidity and mortality rates. However, bacterial drug resistance caused by uncontrolled release of antibiotics seriously restricts clinical efficacy of antibacterial coating. Hence, a local and controlled-release system which can release antibiotics in response to bacterial infected signals is necessary in antibacterial coating. Herein, a multi-stimulus responsive multilayer antibacterial coating was prepared through layer-by-layer (LbL) self-assembly of montmorillonite (MMT), chlorhexidine acetate (CHA) and Poly(protocatechuic acid-polyethylene glycol 1000-bis(phenylboronic acid carbamoyl) cystamine) (PPPB). The coating can be covered on various substrates such as cellulose acetate membrane, polyacrylonitrile membrane, polyvinyl chloride membrane, and polyurethane membrane, proving it is a versatile coating. Under the stimulation of acids, glucose or dithiothreitol, this coating was able to achieve controlled release of CHA and kill more than 99% of Staphylococcus aureus and Escherichia coli (4 × 10⁸ CFU/mL) within 4 h. In the mouse infection model, CHA releasing of the coating was triggered by infected microenvironment to completely kill bacteria, achieving wounds healing within 14 days. Full article

The selection of restorative materials with regard to the longevity and durability of a restoration is of crucial importance for daily dental practice and requires that the degradation of the material in the oral environment can be assessed. The aim of this study was to investigate the extent to which the mechanical properties of four (Esthet X, Ceram X, Filtek Supreme XT, and Filtek Supreme XT flow) resin-based composites (RBCs) alter during storage in saliva substitutes (artificial saliva) for 24 h and 28 days and in the context of simulated, more aggressive clinical conditions, including cycles exposure to de- and remineralization, alcohol, or salivary enzymes. For this purpose, flexural strength and modulus were determined in a three-point bending test (n = 20) followed by Weibull analysis, while quasi-static behavior was evaluated by instrumented indentation techniques. Degradation occurred in all RBCs and all aging protocols and was quantifiable at both macroscopic and microscopic levels. The postulated stabilizing effect on degradation through the incorporation of urethane-based co-monomers into the organic matrix or a higher filler loading is refuted. Even though modern RBCs show high clinical survival rates, biodegradation remains an issue that needs to be addressed. Full article

Osseointegration of implants installed in conjunction with sinus floor elevation might be affected by the presence of residual graft. The implant surface characteristics and the protection of the access window using a collagen membrane might influence the osseointegration. To evaluate these factors, sinus floor elevation was performed in patients using a natural bovine bone grafting material. The access windows were either covered with a collagen membrane made of porcine corium (Mb group) or left uncovered (No-Mb group) and, after six months, two mini-implants with either a moderate rough or turned surfaces were installed. After 3 months, biopsies containing the mini-implants were retrieved, processed histologically, and analyzed. Twenty patients, ten in each group, were included in the study. The two mini-implants were retrieved from fourteen patients, six belonging to the Mb group, and eight to the No-Mb group. No statistically significant differences were found in osseointegration between groups. However, statistically significant differences were found between the two surfaces. It was concluded that implants with a moderately rough surface installed in a composite bone presented much higher osseointegration compared to those with a turned surface. The present study failed to show an effect of the use of a collagen membrane on the access window. Full article

The comparison of the effect of porphyrins of natural and synthetic origin containing the same metal atom on the structure and properties of the semi-crystalline polymer matrix is of current concern. A large number of modifying additives and biodegradable polymers for biomedical purposes, composed of poly(-3-hydroxybutyrate)-porphyrin, are of particular interest because of the combination of their unique properties. The objective of this work are electrospun fibrous material based on poly(-3-hydroxybutyrate) (PHB), hemin (Hmi), and tetraphenylporphyrin with iron (Fe(TPP)Cl). The structure of these new materials was investigated by methods such as optical and scanning electron microscopy, X-ray diffraction analysis, Electron paramagnetic resonance method, and Differential scanning calorimetry. The properties of the electrospun materials were analyzed by mechanical and biological tests, and the wetting contact angle was measured. In this work, it was found that even small concentrations of porphyrin can increase the antimicrobial properties by 12 times, improve the physical and mechanical properties by at least 3.5 times, and vary hydrophobicity by at least 5%. At the same time, additives similar in the structure had an oppositely directed effect on the supramolecular structure, the composition of the crystalline, and the amorphous phases. The article considers assumptions about the nature of such differences due to the influence of Hmi and Fe(TPP)Cl) on the macromolecular and fibrous structure of PHB. Full article

Staphylococcus aureus is one of the major pathogens causing and spreading hospital acquired infections. Since it is highly resistant to new generation antibiotics, novel strategies have to be developed such as the construction of biofunctionalized non-adherent surfaces that will prevent its tethering and subsequent spread in the hospital environment. In this frame, the domain D of protein A (SpAD) of S. aureus has been immobilized onto cellulose acetate scaffolds by using the streptavidin/biotin interaction, in order to study its interaction with the A1 domain of von Willebrand factor (vWF A1), a protein essential for hemostasis, found in human plasma. Subsequently, the biofunctionalized cellulose acetate scaffolds were incubated with S. aureus in the presence and absence of vWF A1 at different time periods and their potential to inhibit S. aureus growth was studied with scanning electron microscopy (SEM). The SpAD biofunctionalized scaffolds perceptibly ameliorated the non-adherent properties of the material, and in particular, the interaction between SpAD and vWF A1 effectively inhibited the growth of S. aureus. Thus, the exhibition of significant non-adherent properties of scaffolds addresses their potential use for covering medical equipment, implants, and stents. Full article

Cement discoplasty has been developed to treat patients with advanced intervertebral disc degeneration. In discoplasty, poly(methylmethacrylate) (PMMA) bone cement is injected into the disc, leading to reduced pain and certain spinal alignment correction. Standard PMMA-cements have much higher elastic modulus than the surrounding vertebral bone, which may lead to a propensity for adjacent fractures. A PMMA-cement with lower modulus might be biomechanically beneficial. In this study, PMMA-cements with lower modulus were obtained using previously established methods. A commercial PMMA-cement (V-steady^®, G21 srl) was used as control, and as base cement. The low-modulus PMMA-cements were modified by 12 vol% (LA12), 16 vol% (LA16) and 20 vol% (LA20) linoleic acid (LA). After storage in 37 °C PBS from 24 h up to 8 weeks, specimens were tested in compression to obtain the material properties. A lower E-modulus was obtained with increasing amount of LA. However, with storage time, the E-modulus increased. Standard and low-modulus PMMA discoplasty were compared in a previously developed and validated computational lumbar spine model. All discoplasty models showed the same trend, namely a substantial reduction in range of motion (ROM), compared to the healthy model. The V-steady model had the largest ROM-reduction (77%), and the LA20 model had the smallest (45%). The average stress at the endplate was higher for all discoplasty models than for the healthy model, but the stresses were reduced for cements with higher amounts of LA. The study indicates that low-modulus PMMA is promising for discoplasty from a mechanical viewpoint. However, validation experiments are needed, and the clinical setting needs to be further considered. Full article

Demineralized dentin matrix (DDM) treated with gamma irradiation (GR) has shown promising results as an allograft without any adverse effects in in vivo and clinical studies. The purpose of this study was to evaluate the effects of 15 and 25 kGy GR on the osteoinductive properties of DDM at extra-skeletal sites. As a control group, non-irradiated DDM powder was implanted into the right subcutaneous tissues of the dorsal thigh muscles of 20 nude mice. DDM powder irradiated with 15 and 25 kGy was implanted into the left side. After two and four weeks, the bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry. After confirming osteoblast- and osteoclast-specific activities by alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) staining, a histological analysis was performed to measure the new bone formation and the number of osteoblasts and osteoclast-like cells on the surface of the DDMs. Histomorphometry was used to calculate the new bone formation area on the surface of the DDM particles (DDMs). The BMD in all the groups increased from two and four weeks without statistically significant differences. The osteoblasts were dominantly activated on DDM without GR, and DDM treated with 25 kGy compared to DDM treated with 15 kGy. Among the groups, new bone formation was identified in all the groups at each time point. In conclusion, GR at doses of 15 and 25 kGy does not affect the osteoinductive properties of DDM powder. Full article

Synthetic bone graft substitutes have attracted increasing attention in tissue engineering. This study aimed to fabricate a novel, bioactive, porous scaffold that can be used as a bone substitute. Strontium and zinc doped nano-hydroxyapatite (Sr/Zn n-HAp) were synthesized by a water-based sol-gel technique. Sr/Zn n-HAp and poly (lactide-co-glycolide) (PLGA) were used to fabricate composite scaffolds by supercritical carbon dioxide technique. FTIR, XRD, TEM, SEM, and TGA were used to characterize Sr/Zn n-HAp and the composite scaffolds. The synthesized scaffolds were adequately porous with an average pore size range between 189 to 406 µm. The scaffolds demonstrated bioactive behavior by forming crystals when immersed in the simulated body fluid. The scaffolds after immersing in Tris/HCl buffer increased the pH value of the medium, establishing their favorable biodegradable behavior. ICP-MS study for the scaffolds detected the presence of Sr, Ca, and Zn ions in the SBF within the first week, which would augment osseointegration if implanted in the body. nHAp and their composites (PLGA-nHAp) showed ultimate compressive strength ranging between 0.4–19.8 MPa. A 2.5% Sr/Zn substituted nHAp-PLGA composite showed a compressive behavior resembling that of cancellous bone indicating it as a good candidate for cancellous bone substitute. Full article

Low-diameter blood vessels are challenging to replace with more traditional synthetic vascular grafts. Therefore, the obvious choice is to try to regenerate small veins and arteries through tissue-engineering approaches. However, the layered structure of native vessels and blood compatibility issues make this a very challenging task. The aim of this study is to create double-layered tubular scaffolds with enhanced anticoagulant properties for the tissue engineering of small blood vessels. The scaffolds were made of a polycaprolactone-based porous outer layer and a polylactide-based electrospun inner layer modified with heparin. The combination of thermally induced phase separation and electrospinning resulted in asymmetric scaffolds with improved mechanical properties. The release assay confirmed that heparin is released from the scaffolds. Additionally, anticoagulant activity was shown through APTT (activated partial thromboplastin time) assay. Interestingly, the endothelial cell culture test revealed that after 14 days of culture, HAECs (human aortic endothelial cell lines) tended to organize in chain-like structures, typical for early stages of vascular formation. In the longer culture, HAEC viability was higher for the heparin-modified scaffolds. The proposed scaffold design and composition have great potential for application in tissue engineering of small blood vessels. Full article

The present study illustrates the manufacturing method of hierarchically porous 3D scaffolds based on åkermanite as a promising bioceramic for stereolithography. The macroporosity was designed by implementing 3D models corresponding to different lattice structures (cubic, diamond, Kelvin, and Kagome). To obtain micro-scale porosity, flame synthesized glass microbeads with 10 wt% of silicone resins were utilized to fabricate green scaffolds, later converted into targeted bioceramic phase by firing at 1100 °C in air. No chemical reaction between the glass microspheres, crystallizing into åkermanite, and silica deriving from silicone oxidation was observed upon heat treatment. Silica acted as a binder between the adjacent microspheres, enhancing the creation of microporosity, as documented by XRD, and SEM coupled with EDX analysis. The formation of ‘spongy’ struts was confirmed by infiltration with Rhodamine B solution. The compressive strength of the sintered porous scaffolds was up to 0.7 MPa with the porosity of 68–84%. Full article

Bone tissue defects resulting from periodontal disease are often treated using guided tissue regeneration (GTR). The barrier membranes utilized here should prevent soft tissue infiltration into the bony defect and simultaneously support bone regeneration. In this study, we designed a degradable poly(l-lactide-co-glycolide) (PLGA) membrane that was surface-modified with cell adhesive arginine-glycine-aspartic acid (RGD) motifs. For a novel method of membrane manufacture, the RGD motifs were coupled with the non-ionic amphiphilic polymer poly(2-oxazoline) (POx). The RGD-containing membranes were then prepared by solvent casting of PLGA, POx coupled with RGD (POx_RGD), and poly(ethylene glycol) (PEG) solution in methylene chloride (DCM), followed by DCM evaporation and PEG leaching. Successful coupling of RGD to POx was confirmed spectroscopically by Raman, Fourier transform infrared in attenuated reflection mode (FTIR-ATR), and X-ray photoelectron (XPS) spectroscopy, while successful immobilization of POx_RGD on the membrane surface was confirmed by XPS and FTIR-ATR. The resulting membranes had an asymmetric microstructure, as shown by scanning electron microscopy (SEM), where the glass-cured surface was more porous and had a higher surface area then the air-cured surface. The higher porosity should support bone tissue regeneration, while the air-cured side is more suited to preventing soft tissue infiltration. The behavior of osteoblast-like cells on PLGA membranes modified with POx_RGD was compared to cell behavior on PLGA foil, non-modified PLGA membranes, or PLGA membranes modified only with POx. For this, MG-63 cells were cultured for 4, 24, and 96 h on the membranes and analyzed by metabolic activity tests, live/dead staining, and fluorescent staining of actin fibers. The results showed bone cell adhesion, proliferation, and viability to be the highest on membranes modified with POx_RGD, making them possible candidates for GTR applications in periodontology and in bone tissue engineering. Full article

Polydimethylsiloxane (PDMS) is an elastomer with excellent optical, electrical and mechanical properties, which makes it well-suited for several engineering applications. Due to its biocompatibility, PDMS is widely used for biomedical purposes. This widespread use has also led to the massification of the soft-lithography technique, introduced for facilitating the rapid prototyping of micro and nanostructures using elastomeric materials, most notably PDMS. This technique has allowed advances in microfluidic, electronic and biomedical fields. In this review, an overview of the properties of PDMS and some of its commonly used treatments, aiming at the suitability to those fields’ needs, are presented. Applications such as microchips in the biomedical field, replication of cardiovascular flow and medical implants are also reviewed. Full article

The development of asymmetric membranes—i.e., matching two fibrous layers with selected composition and morphological properties to mimic both the epidermis and dermis—currently represents one of the most promising strategies to support skin regeneration during the wound healing process. Herein, a new asymmetric platform fabricated by a sequential electrospinning process was investigated. The top layer comprises cross-linked polyvinylalcohol (PVA) nanofibers (NFs)—from water solution—to replicate the epidermis’s chemical stability and wettability features. Otherwise, the bottom layer is fabricated by integrating PVA with wool-keratin extracted via sulfitolysis. This protein is a biocompatibility polymer with excellent properties for dermis-like structures. Morphological characterization via SEM supported by image analysis showed that the asymmetric membrane exhibited average fiber size—max frequency diameter 450 nm, range 1.40 μm—and porosity suitable for the healing process. FTIR-spectrums confirmed the presence of keratin in the bottom layer and variations of keratin-secondary structures. Compared with pure PVA-NFs, keratin/PVA-NFs showed a significant improvement in cell adhesion in in vitro tests. In perspective, these asymmetric membranes could be promisingly used to confine active species (i.e., antioxidants, antimicrobials) to the bottom layer to support specific cell activities (i.e., proliferation, differentiation) in wound healing applications. Full article

Transplantation of differentiated and fully functional neurons may be a better therapeutic option for the cure of neurodegenerative disorders and brain injuries than direct grafting of neural stem cells (NSCs) that are potentially tumorigenic. However, the differentiation of NSCs into a large population of neurons has been a challenge. Nanomaterials have been widely used as substrates to manipulate cell behavior due to their nano-size, excellent physicochemical properties, ease of synthesis, and versatility in surface functionalization. Nanomaterial-based scaffolds and synthetic polymers have been fabricated with topology resembling the micro-environment of the extracellular matrix. Nanocellulose materials are gaining attention because of their availability, biocompatibility, biodegradability and bioactivity, and affordable cost. We evaluated the role of nanocellulose with different linkage and surface features in promoting neuronal differentiation. Nanocellulose coupled with lysine molecules (CNC–Lys) provided positive charges that helped the cells to attach. Embryonic rat NSCs were differentiated on the CNC–Lys surface for up to three weeks. By the end of the three weeks of in vitro culture, 87% of the cells had attached to the CNC–Lys surface and more than half of the NSCs had differentiated into functional neurons, expressing endogenous glutamate, generating electrical activity and action potentials recorded by the multi-electrode array. Full article

Demineralized bone matrix (DBM) is a decalcified allo/xenograft retaining collagen and noncollagenous proteins, which has been extensively used because of its osteoconductive and osteoinductive properties. Calcium sulfate (CaSO₄, CS) is a synthetic bone substitute used in bone healing with biocompatible, nontoxic, bioabsorbable, osteoconductive, and good mechanical characteristics. This study aims to prepare a DBM/CS composite bone graft material in a moldable putty form without compromising the peculiar properties of DBM and CS. For this purpose, firstly, porcine femur was defatted using chloroform/methanol and extracted by acid for demineralization, then freeze-dried and milled/sieved to obtain DBM powder. Secondly, the α-form and β-form of calcium sulfate hemihydrate (CaSO₄·0.5H₂O, CSH) were produced by heating gypsum (CaSO₄·2H₂O). The morphology and particle sizes of α- and β-CSH were obtained by SEM, and their chemical properties were confirmed by EDS, FTIR and XRD. Furthermore, the DBM-based graft was mixed with α- or β-CSH at a ratio of 9:1, and glycerol/4% HPMC was added as a carrier to produce a putty. DBM/CSH putty possesses a low washout rate, good mechanical strength and biocompatibility. In conclusion, we believe that the moldable DBM/CSH composite putty developed in this study could be a promising substitute for the currently available bone grafts, and might have practical application in the orthopedics field as a potential bone void filler. Full article

Peri-implantitis leads to implant failure and decreases long-term survival and success rates of implant-supported prostheses. The pathogenesis of this disease is complex but implant corrosion is believed to be one of the many factors which contributes to progression of this disease. A nanostructured titanium dioxide layer was introduced using anodization to improve the functionality of dental implants. In the present study, we evaluated the corrosion performance of silicon carbide (SiC) on anodized titanium dioxide nanotubes (ATO) using plasma-enhanced chemical vapor deposition (PECVD). This was investigated through a potentiodynamic polarization test and bacterial incubation for 30 days. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to analyze surface morphologies of non-coated and SiC-coated nanotubes. Energy dispersive X-ray (EDX) was used to analyze the surface composition. In conclusion, SiC-coated ATO exhibited improved corrosion resistance and holds promise as an implant coating material. Full article

Subsurface enamel demineralization beneath an intact surface layer or white spots lesions (WSL) can and should be treated with non-invasive procedures to impede the development of a cavitated lesion. We aim to analyze if infiltrative resin improves enamel roughness, microhardness, shear bond strength, and penetration depth. MEDLINE [via Pubmed], Cochrane Central Register of Controlled Trials, Embase, Web of Science, Scholar, and LILACS were searched until May 2021. Methodological quality was assessed using the Joanna Briggs Institute Clinical Appraisal Checklist for Experimental Studies. Pairwise ratio of means (ROM) meta-analyses were carried out to compare the enamel properties after treatment with infiltrative resin on sound enamel and WSLs. From a total of 1604 articles, 48 studies were included. Enamel surface roughness decreased 35% in sound enamel (95%CI: 0.49–0.85, I² = 98.2%) and 54% in WSLs (95%CI: 0.29–0.74, I² = 98.5%). Microhardness reduced 24% in sound enamel (95%CI: 0.73–0.80, I² = 99.1%) and increased by 68% in WSLs (95%CI: 1.51; 1.86, I² = 99.8%). Shear bond strength reduced of 25% in sound enamel (95%CI: 0.60; 0.95, I² = 96.9%) and increased by 89% in WSLs (95%CI: 1.28–2.79, I² = 99.8%). Penetration depth was 65.39% of the WSLs (95%CI: 56.11–74.66, I² = 100%). Infiltrative resins effectively promote evident changes in enamel properties in sound and WSLs. Future studies with long-term follow-ups are necessary to corroborate these results from experimental studies. Full article

Three-dimensional (3D) bioprinting is an emerging fabrication technique to create 3D constructs with living cells. Notably, bioprinting bioinks are limited due to the mechanical weakness of natural biomaterials and the low bioactivity of synthetic peers. This paper presents the development of a natural bioink from chicken eggwhite and sodium alginate for bioprinting cell-laden patches to be used in endothelialized tissue engineering applications. Eggwhite was utilized for enhanced biological properties, while sodium alginate was used to improve bioink printability. The rheological properties of bioinks with varying amounts of sodium alginate were examined with the results illustrating that 2.0–3.0% (w/v) sodium alginate was suitable for printing patch constructs. The printed patches were then characterized mechanically and biologically, and the results showed that the printed patches exhibited elastic moduli close to that of natural heart tissue (20–27 kPa) and more than 94% of the vascular endothelial cells survived in the examination period of one week post 3D bioprinting. Our research also illustrated the printed patches appropriate water uptake ability (>1800%). Full article

Poly(methyl methacrylate) (PMMA) is used to manage bone loss in revision total knee arthroplasty (rTKA). However, the application of PMMA has been associated with complications such as volumetric shrinkage, necrosis, wear debris, and loosening. Glass polyalkenoate cements (GPCs) have potential bone cementation applications. Unlike PMMA, GPC does not undergo volumetric shrinkage, adheres chemically to bone, and does not undergo an exothermic setting reaction. In this study, two different compositions of GPCs (GPCA and GPCB), based on the patented glass system SiO₂-CaO-SrO-P₂O₅-Ta₂O₅, were investigated. Working and setting times, pH, ion release, compressive strength, and cytotoxicity of each composition were assessed, and based on the results of these tests, three sets of samples from GPCA were implanted into the distal femur and proximal tibia of three sheep (alongside PMMA as control). Clinical CT scans and micro-CT images obtained at 0, 6, and 12 weeks revealed the varied radiological responses of sheep bone to GPCA. One GPCA sample (implanted in the sheep for 12 weeks) was characterized with no bone resorption. Furthermore, a continuous bone–cement interface was observed in the CT images of this sample. The other implanted GPCA showed a thin radiolucent border at six weeks, indicating some bone resorption occurred. The third sample showed extensive bone resorption at both six and 12 weeks. Possible speculative factors that might be involved in the varied response can be: excessive Zn²⁺ ion release, low pH, mixing variability, and difficulty in inserting the samples into different parts of the sheep bone. Full article

The finite element method (FEM) represents a computer simulation method, originally used in civil engineering, which dates back to the early 1940s. Applications of FEM have also been used in numerous medical areas and in orthopedic surgery. Computing technology has improved over the years and as a result, more complex problems, such as those involving the spine, can be analyzed. The spine is a complex anatomical structure that maintains the erect posture and supports considerable loads. Applications of FEM in the spine have contributed to the understanding of bone biomechanics, both in healthy and abnormal conditions, such as scoliosis, fractures (trauma), degenerative disc disease and osteoporosis. However, since FEM is only a digital simulation of the real condition, it will never exactly simulate in vivo results. In particular, when it concerns biomechanics, there are many features that are difficult to represent in a FEM. More FEM studies and spine research are required in order to examine interpersonal spine stiffness, young spine biomechanics and model accuracy. In the future, patient-specific models will be used for better patient evaluations as well as for better pre- and inter-operative planning. Full article

Literature in the field of stem cell therapy indicates that, when stem cells in a state of single-cell suspension are injected systemically, they show poor in vivo survival, while such cells show robust cell survival and regeneration activity when transplanted in the state of being attached on a biomaterial surface. Although an attachment-deprived state induces anoikis, when cell-surface engineering technology was adopted for stem cells in a single-cell suspension state, cell survival and regenerative activity dramatically improved. The biochemical signal coming from ECM (extracellular matrix) molecules activates the cell survival signal transduction pathway and prevents anoikis. According to the target disease, various therapeutic cells can be engineered to improve their survival and regenerative activity, and there are several types of biomaterials available for cell-surface engineering. In this review, biomaterial types and application strategies for cell-surface engineering are presented along with their expected efficacy. Full article

Electrical stimulation (ES) can serve as a therapeutic modality accelerating the healing of wounds, particularly chronic wounds which have impaired healing due to complications from underlying pathology. This review explores how ES affects the cellular mechanisms of wound healing, and its effectiveness in treating acute and chronic wounds. Literature searches with no publication date restrictions were conducted using the Cochrane Library, Medline, Web of Science, Google Scholar and PubMed databases, and 30 full-text articles met the inclusion criteria. In vitro and in vivo experiments investigating the effect of ES on the general mechanisms of healing demonstrated increased epithelialization, fibroblast migration, and vascularity around wounds. Six in vitro studies demonstrated bactericidal effects upon exposure to alternating and pulsed current. Twelve randomized controlled trials (RCTs) investigated the effect of pulsed current on chronic wound healing. All reviewed RCTs demonstrated a larger reduction in wound size and increased healing rate when compared to control groups. In conclusion, ES therapy can contribute to improved chronic wound healing and potentially reduce the financial burden associated with wound management. However, the variations in the wound characteristics, patient demographics, and ES parameters used across studies present opportunities for systematic RCT studies in the future. Full article

Recently, the modification of the initial structure of biopolymers, mainly chitosan, has been gaining importance with a view to obtain functional forms with increased practicality and specific properties enabling their use in tissue engineering. Therefore, in this article, the properties (structural and biological) of thermosensitive hydrogels obtained from chitosan lactate/chloride and two types of crosslinking agents (β-glycerol phosphate disodium salt pentahydrate and uridine 5′-monophosphate disodium salt) are discussed. The aim of the research is to identify changes in the structure of the biomaterials during conditioning in water. Structural investigations were carried out by FTIR spectroscopy. The crystallinity of gels was determined by X-ray diffraction analysis. The biocompatibility (evaluation of cytotoxicity and genotoxicity) of chitosan hydrogels was investigated by contact with human colon adenocarcinoma cell line for 48 h. The cytotoxicity was verified based on the colorimetric resazurin assay, and the genotoxicity was checked by the comet assay (percentage of DNA in the comet tail). The conducted research showed that the analyzed types of chitosan hydrogels are non-cytotoxic and non-genotoxic materials. The good biocompatibility of chitosan hydrogels surfaces makes them interesting scaffolds with clinical potential in tissue regeneration engineering. Full article

One of the most serious complications following joint replacement surgeries are periprosthetic infections (PIs) arising from the adhesion of bacteria to the artificial joint. Various types of titanium–aluminum–vanadium (TiAl6V4) alloy surface modifications (coatings with silver (Ag), titanium nitride (TiN), pure titanium (cpTi), combinations of cpTi and hydroxyapatite (HA), combinations of cpTi and tricalcium phosphate (TCP), and a rough-blasted surface of TiAl6V4) have been investigated to assess their effects on biofilm development. Biofilms were grown, collected, and analyzed after 48 h to measure their protein and glucose content and the cell viability. Biofilm-associated genes were also monitored after 48 h of development. There was a distinct difference in the development of staphylococcal biofilms on the surfaces of the different types of alloy. According to the findings of this study, the base alloy TiAl6V4 and the TiN-coated surface are the most promising materials for biofilm reduction. Rough surfaces are most favorable when it comes to bacterial infections because they allow an easy attachment of pathogenic organisms. Of all rough surfaces tested, rough-blasted TiAl6V4 was the most favorable as an implantation material; all the other rough surfaces showed more distinct signs of inducing the development of biofilms which displayed higher protein and polysaccharide contents. These results are supported by RT-qPCR measurements of biofilm associated genes for Staphylococcus aureus (icaA, icaC, fnbA, fnbB, clfB, atl) and Staphylococcus epidermidis (atle, aap). Full article

Single tooth implant restorations in the aesthetic area are a demanding challenge. If a complete osseointegration is mandatory, the final result has to result in a higher standard of biomimetic and soft tissue health among natural teeth. This outcome is traditionally pursued by cementing crowns over individualized abutments. However, in recent years, the need for controlling peri-implant health and the preference towards a retrievable solution has led to an increase in screw-retained crowns, which is not always applicable when the implant axis is not ideal. In the aesthetic area, the use of a novel technical solution represented by the angled screw channel (ASC) of the abutment has been proposed in order to match the advantages of the screwed solution with the aesthetic demands. The aim of this study was to compare ASC crowns to cemented crowns (CC) in single implant restorations using the white esthetic score (WES) and pink esthetic score (PES) at the crown delivery and at a follow-up of a minimum of 2 years. Peri-implant health and marginal bone loss (MBL) were also evaluated. The mean follow-up was 44.3 months, with a mean MBL of 0.22 mm in the ASC group and 0.29 mm in the CC group. The total WES/PES score was 16.6 for ASC, compared with 17.3 for CC at baseline, and 16.2 and 17.1, respectively, at follow-up. Both of the groups reached a high WES/PES, and this was maintained over time, without signs of peri-implant diseases or bone loss, regardless of the choice of connection. In conclusion, ASC can be adopted in cases where the implant axis is not ideal, with aesthetic and functional results that are comparable to implants restored by cemented crowns. Full article

Ethosomes^® have been proposed as potential intra-articular drug delivery devices, in order to obtain a longer residence time of the delivered drug in the knee joint. To this aim, the conventional composition and preparation method were modified. Ethosomes^® were prepared by using a low ethanol concentration and carrying out a vesicle extrusion during the preparation. The modified composition did not affect the deformability of ethosomes^®, a typical feature of this colloidal vesicular topical carrier. The maintenance of sufficient deformability bodes well for an effective ethosome^® application in the treatment of joint pathologies because they should be able to go beyond the pores of the dense collagen II network. The investigated ethosomes^® were inserted in a three-dimensional network of thermo-sensitive poloxamer gel (EtoGel) to improve the residence time in the joint. Rheological experiments evidenced that EtoGel could allow an easy intra-articular injection at room temperature and hence transform itself in gel form at body temperature into the joint. Furthermore, EtoGel seemed to be able to support the knee joint during walking and running. In vitro studies demonstrated that the amount of used ethanol did not affect the viability of human chondrocytes and nanocarriers were also able to suitably interact with cells. Full article

Titanium alloys are widely used for biomedical applications due to their good biocompatibility. Nevertheless, they cannot be used for balloon expandable stents due to a lack of ductility compared to cobalt-chromium (Co-Cr) alloys and stainless steels. In this study, a new highly deformable Ti-16Nb-8Mo alloy was designed for such an application. However, the biological performance of a stent material is strongly influenced by the effect exerted on the behavior of endothelial cells. Therefore, the cellular responses of human umbilical vein endothelial cells (HUVECs), including morphological characteristics, cell viability and proliferation, and functional markers expression, were investigated to evaluate the biocompatibility of the alloy in the present study. The in vitro results demonstrated the suitability of this alloy for use as endovascular stents. Full article

Oral diseases and periodontitis in particular are a major health burden worldwide, because of their association with various systemic diseases and with conditions such as peri-implantitis. Attempts have been made over the years to reverse bone loss due to the host disproportionate inflammatory response and to prevent failure of dental implants. To this end, the use of biomaterials functionalized with molecules characterized by anti-inflammatory and antioxidant properties could represent a new frontier for regenerating functional periodontal tissues. In this study, a new ceramic granulated biomaterial, named Synergoss Red (SR), functionalized with a polyphenolic mixture extracted from pomace of the Croatina grape variety, is introduced. Following a preliminary in-depth characterization of the extract by HPLC analysis and of the biomaterial surface and composition, we performed evaluations of cytocompatibility and a biological response through in vitro assays. The anti-inflammatory and antioxidant properties of the identified phenolic molecules contained in SR were shown to downregulate inflammation in macrophages, to stimulate in osteoblast-like cells the expression of genes involved in deposition of the early bone matrix, and to mitigate bone remodeling by decreasing the RANKL/OPG ratio. Thanks to its cytocompatibility and assorted beneficial effects on bone regeneration, SR could be considered an innovative regenerative approach in periodontal therapy. Full article

Background: The study aimed at assessing the mucoadhesive properties and the barrier effect of a formulation, labelled as AL2106, containing sodium chondroitin sulfate (ChS), xyloglucan from tamarind seed extract, and glycerol, by evaluating the capacity to adhere to a layer of mucin, the rheological synergism and the barrier effect in comparison to the marketed Esoxx One medical device. AL2106 is a medical device distributed by Alfasigma SpA, Italy with REF FTP57 (Manufacturer: Labomar SpA); it is analogous to Esoxx One medical device: the two products are drinkable solutions that, after swallowing, adhere to the esophageal mucosa, protecting it from the corrosive effect of the gastric acid reflux. AL2106 has been conceived to be better performing in terms of duration of the barrier effect compared to Esoxx One. Methods: The mucoadhesive properties, rheological behavior, buffering capacity against acidity, and film-forming ability with the resultant protecting effect on esophagus mucosa (caffeine permeation test) was compared between the two products. Results: The mucoadhesivity of the formulations was shown in vitro: both remained adherent to a mucin layer, also when the support was rotated by 90°, and when the film layer was washed with water, intended to simulate the washout due to swallowing. AL2106 showed a good buffering efficacy, being able to absorb at least 50% of its weight of 0.03 M HCl while maintaining the pH above 4. The film-forming effect and barrier properties of AL2106 and Esoxx One were confirmed by an in vitro study on reconstructed human esophageal epithelium. A greater film-forming efficacy of AL2106, lasting for at least 5 h, than Esoxx One was observed. Noteworthy, the barrier function of esophageal tissues was shown to be preserved after the application of both formulations. Conclusions: The combination of ChS with the mucoadhesive glycerol−xyloglucan complex and other excipients, which contribute to the barrier effect and to mucoadhesion, contained in AL2106, allowed a longer-lasting protective effect than Esoxx One, proving its effectivity and safety for oral use. Full article