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In this work an innovative formulation of bone cement for the treatment of bone tumor and its associated complications has been designed by preparing a new class of Fe3O4–Ag nanostructures, using gallic acid as a reducing agent. The obtained nanoparticles have been introduced in polymethyl methacrylate (PMMA)-based composite cement evaluating the insertion of different amounts and the use of different mixing methods. The morphology, the composition and the antibacterial effect of Fe3O4–Ag nanostructures have been investigated together with the morphology, the composition, the mechanical properties of the nanoparticles-containing composite cements as well as their antibacterial effect. The obtained results revealed a good antimicrobial effect of Fe3O4–Ag nanostructures, a significant influence of their amount and of the used mixing method on the particles dispersion and agglomeration in the PMMA matrix and, as a result, on the mechanical properties. In particular, a better dispersion of nanoparticles was obtained by using the mechanical mixing, reducing the tendency to agglomerate. The increase of nanoparticles amount induced a slight decrease of the mechanical properties; however, the introduction of 10% w/w of Fe3O4–Ag allowed to improve the composites ability to reduce the bacteria adhesion.

Surface bearing of total hip arthroplasty (THA) still is a strong subject of study due to the relatively high rate of failures caused by a multiplicity of factors including surgical technique, patient's attitude, and type/characteristics of the materials used (metal, ceramics, polyethylene) with their specific risk factors. Fractures of the ceramic components are rare but catastrophic events, with many concerns among the orthopaedic surgeons. Such complication is usually evaluated from a clinical viewpoint; this study provides a materials scientist's complementary perspective and comprehensively evaluates the surface and the mechanism of rupture of the ceramic liner in two cases with different ceramics (Biolox Forte and Biolox Delta) after ceramic-on-ceramic THA. The morphological and compositional analyses of the ceramic components were performed by field-emission scanning electron microscopy (FESEM) and energy dispersive spectroscopy (EDS), along with macroscopic pictures. The SEM analysis of the ceramic liner showed many wear signs in all directions, while the EDS revealed the presence of titanium near to the fracture border, which might be interpreted as a consequence of the catastrophic contact between ceramic liner and metal back. Biolox Delta and Biolox Forte ceramic liners showed different patterns of fracture and surface modifications that are illustrated and discussed.

Bioactive silicate glass scaffolds were fabricated by a robocasting process in which all the movements of the printing head were programmed by compiling a script (text file). A printable ink made of glass powder and Pluronic F-127, acting as a binder, was extruded to obtain macroporous scaffolds with a grid-like three-dimensional structure. The scaffold architecture was investigated by scanning electron microscopy and microtomographic analysis, which allowed quantifying the microstructural parameters (pore size 150–180 μm and strut diameter 300 μm). In vitro tests in simulated body fluid (SBF) confirmed the apatite-forming ability (i.e., bioactivity) of the scaffolds. The compressive strength (around 10 MPa for as-produced scaffolds) progressively decreased during immersion in SBF (3.3 MPa after 4 weeks) but remains acceptable for bone repair applications. Taken together, these results (adequate porosity and mechanical strength as well as bioactivity) support the potential suitability of the prepared scaffolds for bone substitution.

The traditional silicate bioactive glasses exhibit poor thermal processability, which inhibits fiber drawing or sintering into scaffolds. The composition of the silicate glasses has been modified to enable hot processing. However, the hot forming ability is generally at the expense of bioactivity. Metaphosphate glasses, on the other hand, possess excellent thermal processability, congruent dissolution, and a tailorable degradation rate. However, due to the layer-by-layer dissolution mechanism, cells do not attach to the material surface. Furthermore, the congruent dissolution leads to a low density of OH groups forming on the glass surface, limiting the adsorption of proteins. It is well regarded that the initial step of protein adsorption is critical as the cells interact with this protein layer, rather than the biomaterial itself. In this paper, we explore the possibility of improving protein adsorption on the surface of phosphate glasses through a variety of surface treatments, such as washing the glass surface in acidic (pH 5), neutral, and basic (pH 9) buffer solutions followed or not by a treatment with (3-aminopropyl)triethoxysilane (APTS). The impact of these surface treatments on the surface chemistry (contact angle, ζ-potential) and glass structure (FTIR) was assessed. In this manuscript, we demonstrate that understanding of the material surface chemistry enables to selectively improve the adsorption of albumin and fibronectin (used as model proteins). Furthermore, in this study, well-known silicate bioactive glasses (i.e., S53P4 and 13-93) were used as controls. While surface treatments clearly improved proteins adsorption on the surface of both silicate and phosphate glasses, it is of interest to note that protein adsorption on phosphate glasses was drastically improved to reach similar protein grafting ability to the silicate bioactive glasses. Overall, this study demonstrates that the limited cell/phosphate glass biological response can easily be overcome through deep understanding and control of the glass surface chemistry. publishedVersion

Proper microstructural and transport properties are fundamental requirements for a suitable scaffold design and realization in tissue engineering applications. Scaffold microstructure (i.e. pore size, shape and distribution) and transport properties (i.e. intrinsic permeability), are commonly recognized as the key parameters related to the biological performance, such as cell attachment, penetration depth and tissue vascularization. While pore characteristics are relatively easy to asses, accurate and reliable evaluation of permeability still remains a challenge. In the present study, the microstructural properties of foam-replicated bioactive glass-derived scaffolds (basic composition 47.5SiO2–2.5P2O5–20CaO–10MgO–10Na2O–10K2O mol.%) were determined as function of the sintering temperature within the range 600-850°C, identified on the basis of thermal analyses that were previously performed on the material. Scaffolds with total porosity between 55 and 84 vol.% and trabecular-like architecture were obtained, with pore morphological features varying according to the sintering temperature. Mathematical modelling, supported by micro-computed tomography (μ-CT) imaging, was implemented to selectively investigate the effect of different pore features on intrinsic permeability, which was determined by laminar airflow alternating pressure wave drop measurements and found to be within 0.051-2.811·10−10 m2. The calculated effective porosity of the scaffolds was in the range of 46 to 66 vol.%, while the average pore diameter assessed by μ-CT varied between 220 and 780 μm, where the values in the lower range were observed for higher sintering temperatures (750-850°C). Experimental results were critically discussed by means of a robust statistical analysis. Finally, the complete microstructural characterization of the scaffolds was achieved by applying the general constitutive equation based on Forchheimer's theory.

Bud extracts are a new category of vegetal products, which are used in gemmotherapy. These products are liquid preparation sources of bioactive molecules (phytochemicals) and are used in medicine as health-promoting agents. Rosa canina is a medicinal plant belonging to the family Rosaceae. The R. canina bud extracts, in particular, possess anti-inflammatory and antioxidant activities due to the presence of flavonoids and other phenolic compounds. The combination of R. canina bud extracts with biomaterials can be promising for obtaining multifunctional materials carrying both inorganic and biological properties. In this work, a protocol of functionalization has been properly designed, for the first time in the literature, in order to graft various bud extracts of R. canina to a silica-based bioactive glass (CEL2). The Folin-Ciocalteu method was used to determine the redox capacity of total polyphenols in the extracts and on functionalized solid samples. X-ray photoelectron spectroscopy analysis and fluorescence microscopy were employed to investigate the presence of phenol substances on the material surface. Bioactivity (in terms of ability of inducing hydroxyapatite precipitation) has been investigated by soaking the samples, with or without functionalization, in simulated body fluid. The presence of the polyphenols from bud extracts not only preserved glass bioactivity but even enhanced it. In particular, the solution obtained from the byproducts of primary extraction in glycerol macerate showed the best performances. Moreover, the presence and antioxidant activity of bud extract compounds on the material surface after grafting demonstrate the possibility of combining the glass inorganic bioactivity with the biomolecule-specific properties, making possible a local action at the implant site. The promising results reported in this work pave the way for the realization of new multifunctional materials with a green approach.

Since 2006, the foam replica method has been commonly recognized as a valuable technology for the production of highly porous bioactive glass scaffolds showing three-dimensional, open-cell structures closely mimicking that of natural trabecular bone. Despite this, there are important drawbacks making the usage of foam-replicated glass scaffolds a difficult achievement in clinical practice; among these, certainly the high operator-dependency of the overall manufacturing process is one of the most crucial, limiting the scalability to industrial production and, thus, the spread of foam-replicated synthetic bone substitutes for effective use in routine management of bone defect. The present review opens a window on the versatile world of the foam replica technique, focusing the dissertation on scaffold properties analyzed in relation to various processing parameters, in order to better understand which are the real issues behind the bottleneck that still puts this technology on the Olympus of the most used techniques in laboratory practice, without moving, unfortunately, to a more concrete application. Specifically, scaffold morphology, mechanical and mass transport properties will be reviewed in detail, considering the various templates proposed till now by several research groups all over the world. In the end, a comprehensive overview of in vivo studies on bioactive glass foams will be provided, in order to put an emphasis on scaffold performances in a complex three-dimensional environment.

Bioactive glasses are the materials of choice in the field of bone regeneration. Antioxidant properties of interest to limit inflammation and foreign body reactions have been conferred to bioactive glasses by the addition of appropriate ions (such as Ce or Sr). On the other hand, the antioxidant activity of bioactive glasses without specific ion/molecular doping has been occasionally cited in the literature but never investigated in depth. In the present study, three silica-based bioactive glasses have been developed and characterized for their surface properties (wettability, zeta potential, chemical composition, and reactivity) and radical scavenging activity in the presence/absence of cells. For the first time, the antioxidant activity of simple silica-based (SiO2–CaO–Na2O) bioactive glasses has been demonstrated.

In this study, the mechanical properties of glass scaffolds manufactured by robocasting are investigated through micro computed tomography ($$\mu -CT$$μ-CT) based finite element modeling. The scaffolds are obtained by printing fibers along two perpendicular directions on parallel layers with a$$90^\circ $$90∘tilting between two adjacent layers. A parametric study is first presented with the purpose to assess the effect of the major design parameters on the elastic and strength properties of the scaffold; the mechanical properties of the 3D printed scaffolds are eventually estimated by using the$$\mu -CT$$μ-CTdata with the aim of assessing the effect of defects on the final geometry which are intrinsic in the manufacturing process. The macroscopic elastic modulus and strength of the scaffold are determined by simulating a uniaxial compressive test along the direction which is perpendicular to the layers of the printed fibers. An iterative approach has been used in order to determine the scaffold strength. A partial validation of the computational model has been obtained through comparison of the computed results with experimental values presented in [10] on a ceramic scaffold having the same geometry. All the results have been presented as non-dimensional values. The finite element analyses have shown which of the selected design parameters have the major effect on the stiffness and strength, being the porosity and fiber shifting between adjacent layers the most important ones. The analyses carried out on the basis of the$$\mu -CT$$μ-CTdata have shown elastic modulus and strength which are consistent with that found on ideal geometry at similar macroscopic porosity.Graphic AbstractIn this work, elastic and strength properties of glass-ceramic Bone Tissue Engineering scaffolds manufactured by robocasting are investigated through micro-CT based finite element models. An incremental simulation using a multi-grid finite element solver has been implemented to perform a parametric study on the effect of the major geometrical parameters of the scaffold design as well as the effect. Eventually, the effect of the geometrical imperfections deriving from the 3D printing process has been investigated by means of micro-CT image-based models. The porosity and the shifting between adjacent layers play the dominant role in determing elasticity and strength of the scaffolds. The elastic and strength properties of 3D-printed real scaffold were assessed to be consistent those obtained from the idealized geometric models, at least for the subdomain used in this study.

The intrinsic brittleness of bioactive glasses (BGs) is one of the main barriers to the widespread use of three-dimensional porous BG-derived bone grafts (scaffolds) in clinical practice. Among all the available strategies for improving the mechanical properties of BG-based scaffolds, strut densification upon sintering treatments at high temperatures represents a relatively easy approach, but its implementation might lead to undesired and poorly predictable decrease in porosity, mass transport properties and bioactivity resulting from densification and devitrification phenomena occurring in the material upon heating. The aim of the present work was to investigate the sinter-crystallization of a highly bioactive SiO2-P2O5-CaO&ndash, MgO&ndash, Na2O&ndash, K2O glass (47.5B composition) in reference to its suitability for the fabrication of bonelike foams. The thermal behavior of 47.5B glass particles was investigated upon sintering at different temperatures in the range of 600&ndash, 850 &deg, C by means of combined thermal analyses (differential thermal analysis (DTA) and hot-stage microscopy (HSM)). Then, XRD measurements were carried out to identify crystalline phases developed upon sintering. Finally, porous scaffolds were produced by a foam replica method in order to evaluate the effect of the sintering temperature on the mechanical properties under compression loading conditions. Assessing a relationship between mechanical properties and sintering temperature, or in other words between scaffold performance and fabrication process, is a key step towards the rationale design of optimized scaffolds for tissue repair.

After years of research on the ability of glass-ceramics in bone regeneration, this family of biomaterials has shown revolutionary potentials in a couple of emerging applications such as cancer treatment. Although glass-ceramics have not yet reached their actual potential in cancer therapy, the relevant research activity is significantly growing in this field. It has been projected that this idea and the advent of magnetic bioactive glass-ceramics and mesoporous bioactive glasses could result in major future developments in the field of cancer. Undoubtedly, this strategy needs further developments to better answer the critical questions essential for clinical usage. This review aims to address the existing research developments on glass-ceramics for cancer treatment, starting with the current status and moving to future advances. Statement of Significance Although glass-ceramics have not yet reached their potential in cancer therapy, research activity is significantly growing. It has been speculated that this idea and the advent of modern glass-ceramics could result in significant future advances. Undoubtedly, this strategy needs further investigations and many critical questions have to be answered before it can be successfully applied for cancer treatment. This paper reviews the current state-of-the-art, starting with current products and moving onto recent developments in this field. According to our knowledge, there is a lack of a systematic review on the importance and developments of magnetic bioactive glass-ceramics and mesoporous bioactive glasses for cancer treatment, and it is expected that this review will be of interest to those working in this area.

Bioactive glasses have been widely investigated for their ability to release ions with therapeutic effect. In this paper, a silica based bioactive glass was doped with a low amount of tellurium dioxide (1 and 5 mol%) to confer antibacterial and antioxidant properties. The obtained glasses were characterized in terms of morphology, composition, structure, characteristic temperatures and in vitro bioactivity. Moreover, comprehensive analyses were carried out to estimate the cytocompatibility, the antibacterial and antioxidant properties of Te-doped glasses. The performed characterizations demonstrated that the Te insertion did not interfere with the amorphous nature of the glass, the substitution of SiO2 with TeO2 led to a slight decrease in Tg and a TeO2 amount higher than 1 mol% can induce a change in the primary crystal field. In vitro bioactivity test demonstrated the Te-doped glass ability to induce the precipitation of hydroxyapatite. Finally, the biological characterization showed a strong antibacterial and antioxidant effects of Te-containing glasses in comparison with the control glass, demonstrating that Te is a promising element to enhance the biological response of biomaterials.

Bioactive glass coatings were deposited for the first time onto wood-derived biocarbon scaffolds using the sol-gel technique. The cellular pore structure of the beech wood was retained during the sol-gel coating process. Owing to the presence of the bioactive glass layer, the originally bioinert biocarbon scaffold was fully covered with newly-formed hydroxyapatite (HA) upon soaking in simulated body fluid. The ability to form HA is generally accepted as the proof of in vitro bioactivity. This opens up the possible application of wood-derived scaffolds in biomedicine (bone repair) and biotechnology.

Sol-gel route has shown its enormous potential in tissue engineering applications as an advantageous method for the production of bioactive glasses aimed at regenerating both hard and soft tissues. This review discusses the chemical aspects of the method with emphasis on the morphological, chemical, mechanical, and biological properties of sol-gel derived materials. The attention will be particularly focused on sol-gel bioactive glasses and sol-gel foam scaffolds for bone regeneration. The advantages deriving from the versatility of the sol-gel method compared to the traditional melt-quenching route will be underlined in terms of bioactivity, compositions, and processing parameters.

Stable suspensions of spherical 10–15 nm superparamagnetic iron oxide nanoparticles (SPIONs) have been synthetized by co-precipitation, stabilized with citric acid, surface functionalized with aminopropyltriethoxysilane (APTES) and finally decorated with ultra-small gold nanoparticles (GNPs) by in situ reduction of a soluble gold salt (HAuCl 4 ), obtaining well dispersed SPIONs-GNPs colloids. The morphology, size and stability of the SPIONs-GNPs suspensions have been controlled by adjusting the molar ratio of the reagents (Fe/HAuCl 4 and Fe/APTES). The synthesis route differs from that typically found in literature, using tunable chelating layer modifications (such as citric acid and –NH 2 groups) of the magnetic core, depositing GNPs on the amine-functionalized iron oxide surface without the use of a specific reducing agent, and tuning the process pH and temperature. An explanation of how the different chemical species involved in the synthesis route could be responsible for the reducing action has been provided. The SPIONs-GNPs colloids have been characterized after each synthesis step by Transmission Electron Microscopy (TEM), Scanning Transmission Electron Microscopy (STEM), energy-dispersive X-ray spectroscopy (EDXS), Fourier transform infrared spectroscopy (FTIR), ζ Potential measurements, magnetic measurements with a vibrating-sample magnetometer (VSM) and UV–VIS spectroscopy. The SPIONs-GNPs colloids showed magnetoplasmonic behaviors since they maintained the plasmonic properties of GNPs and the superparamagnetic response of iron oxide NPs.

In this work, hybrid melanin-coated bioactive glass-ceramic multifunctional scaffolds were developed and characterized in terms of mechanical strength, in vitro bioactivity in simulated body fluid (SBF) and ability to load ibuprofen. The coated scaffolds exhibited an accelerated bioactivity in comparison with the uncoated ones, being able of developing hydroxyapatite-like crystals after 7days soaking in simulated body fluid (SBF). Besides its positive influence on the scaffolds bioactivity, the melanin coating was able to enhance their mechanical properties, increasing the initial compressive strength by a factor of >2.5. Furthermore, ibuprofen was successfully loaded on this coating, allowing a controlled drug release of the anti-inflammatory agent.

One of the goals for the development of more effective cancer therapies with reduced toxic side effects is the optimization of innovative treatments to selectively kill tumor cells. The use of nanovectors loaded with targeted therapeutic payloads is one of the most investigated strategies. In this paper superparamagnetic iron oxide nanoparticles (SPIONs) coated by a silica shell or uncoated, were functionalized with single-layer and bi-layer conjugated linoleic acid (CLA). Silica was used to protect the magnetic core from oxidation, improve the stability of SPIONs and tailor their surface reactivity. CLA was used as novel grafting biomolecule for its anti-tumor activity and to improve particle dispersibility. Mouse breast cancer 4T1 cells were treated with these different SPIONs. SPIONs functionalized with the highest quantity of CLA and coated with silica shell were the most dispersed. Cell viability was reduced by SPIONs functionalized with CLA in comparison with cells which were untreated or treated with SPIONs without CLA. As regards the types of SPIONs functionalized with CLA, the lowest viability was observed in cells treated with uncoated SPIONs with the highest quantity of CLA. In conclusion, the silica shell free SPIONs functionalized with the highest amount of CLA can be suggested as therapeutic carriers because they have the best dispersion and ability to decrease 4T1 cell viability.

Bioactive glasses, invented by Prof. Larry L. Hench in the late 1960s, have revolutionized the field of biomaterials as they were shown to tightly bond to both hard and soft living tissues and to stimulate cells towards a path of regeneration and self-repair. However, due to their relatively poor mechanical properties (brittleness, low bending strength and fracture toughness), they are generally unsuitable for load-bearing applications. On the other hand, bioactive glasses have been successfully applied as coatings on the surface of stronger/tougher substrates to combine adequate mechanical properties with high bioactivity and, in some cases, additional extrafunctionalities (e.g. antibacterial properties, drug release). After giving a short overview of the main issues concerning the fabrication of glass coatings, this review provides a state-of-the-art picture in the field and specifically discusses the development of bioactive and hierarchical coatings on 3D porous scaffolds, joint prostheses, metallic substrates (e.g. wires or nails) for orthopedic fixation, polymeric meshes and sutures for wound healing, ocular implants and percutaneous devices.

Bioactive sol-gel glasses are attractive biomaterials from both technological and functional viewpoints as they require lower processing temperatures compared to their melt-derived counterparts and exhibit a high specific surface area due to inherent nanoporosity. However, most of these materials are based on relatively simple binary or ternary oxide systems since the synthesis of multicomponent glasses via sol-gel still is a challenge. This work reports for the first time the production and characterization of sol-gel materials based on a six-oxide basic system (SiO2&ndash, P2O5&ndash, CaO&ndash, MgO&ndash, Na2O&ndash, K2O). It was shown that calcination played a role in inducing the formation of crystalline phases, thus generating glass-ceramic materials. The thermal, microstructural and textural properties, as well as the in vitro bioactivity, of these sol-gel materials were assessed and compared to those of the melt-derived counterpart glass with the same nominal composition. In spite of their glass-ceramic nature, these materials retained an excellent apatite-forming ability, which is key in bone repair applications.

The use of three-dimensional (3D) scaffolds is recognized worldwide as a valuable biomedical approach for promoting tissue regeneration in critical-size bone defects. Over the last 50 years, bioactive glasses have been intensively investigated in a wide range of different clinical applications, from orthopedics to soft tissue healing. Bioactive glasses exhibit the unique capability to chemically bond to the host tissue and, furthermore, their processing versatility makes them very appealing due to the availability of different manufacturing techniques for the production of porous and interconnected synthetic bone grafts able to support new tissue growth over the whole duration of the treatment. As a novel contribution to the broad field of scaffold manufacturing, we report here an effective and relatively easy method to produce silicate glass-derived scaffolds by using, for the first time in the biomedical field, dolomite powder as a foaming agent for the formation of 3D bone-like porous structures. Morphological/structural features, crystallization behavior, and in vitro bioactivity in a simulated body fluid (SBF) were investigated. All the tested scaffolds were found to fulfil the minimum requirements that a scaffold for osseous repair should exhibit, including porosity (65&ndash, 83 vol.%) and compressive strength (1.3&ndash, 3.9 MPa) comparable to those of cancellous bone, as well as hydroxyapatite-forming ability (bioactivity). This study proves the suitability of a dolomite-foaming method for the production of potentially suitable bone grafts based on bioactive glass systems.

Bioactive materials should maintain their properties during implantation and for long time in contact with physiological fluids and tissues. In the present research, five different bioactive materials (a bioactive glass and four different chemically treated bioactive titanium surfaces) have been studied and compared in terms of mechanical stability of the surface bioactive layer-substrate interface, their long term bioactivity, the type of hydroxyapatite matured and the stability of the hydroxyapatite-surface bioactive layer interface. Numerous physical and chemical analyses (such as Raman spectroscopy, macro and micro scratch tests, soaking in SBF, Field Emission Scanning Electron Microscopy equipped with Energy Dispersive Spectroscopy (SEM-EDS), zeta potential measurements and Fourier Transformed Infra-Red spectroscopy (FTIR) with chemical imaging) were used. Scratch measurements evidenced differences among the metallic surfaces concerning the mechanical stability of the surface bioactive layer-substrate interface. All the surfaces, despite of different kinetics of bioactivity, are covered by a bone like carbonate-hydroxyapatite with B-type substitution after 28 days of soaking in SBF. However, the stability of the apatite layer is not the same for all the materials: dissolution occurs at pH around 4 (close to inflammation condition) in a more pronounced way for the surfaces with faster bioactivity together with detachment of the surface bioactive layer. A protocol of characterization is here suggested to predict the implant-bone interface stability.

Nowadays, there is a large amount of research aimed at improving the multifunctional behavior of the biomaterials for bone contact, including the concomitant ability to induce apatite formation (bioactivity), fast and effective osteoblasts colonization, and antibacterial activity. The aim of this study is to develop antibacterial and bioactive surfaces (Ti6Al4V alloy and a silica-based bioactive glass) by chemical doping with strontium and/or silver ions. The surfaces were characterized by Scanning Electron Microscopy equipped with Energy Dispersive X ray Spectroscopy (SEM-EDS), X-ray photoelectron spectroscopy (XPS), and Transmission Electron Microscopy (TEM). To better focus on the cells&ndash, bacteria competition for the implant surface, in addition to the standard assays for the evaluation of the bacteria adhesion (ISO22196) and for single-cell cultures or biofilm formation, an innovative set of co-cultures of cells and bacteria is here proposed to simulate a competitive surface colonization. The results suggest that all the bioactive tested materials were cytocompatible toward the bone progenitor cells representative for the self-healing process, and that the doped ones were effective in reducing the surface colonization from a pathogenic drug-resistant strain of Staphylococcus aureus. The co-cultures experiments demonstrated that the doped surfaces were able to protect the adhered osteoblasts from the bacteria colonization as well as prevent the infection prior to the surface colonization by the osteoblasts.

Bioactive glasses (BGs) are routinely being used as potent materials for hard and soft tissue engineering applications; however, improving their biological activities through surface functionalization and modification has been underestimated so far. The surface characteristics of BGs are key factors in determining the success of any implanted BG-based material in vivo since they regulate the affinity and binding of different biological macromolecules and thereby the interactions between cells and the implant. Therefore, a number of strategies using chemical agents (e.g., glutaraldehyde, silanes) and physical methods (e.g., laser treatment) have been evaluated and applied to design properly, tailor, and improve the surface properties of BGs. All these approaches aim at enhancing the biological activities of BGs, including the induction of cell proliferation and subsequent osteogenesis, as well as the inhibition of bacterial growth and adhesion, thereby reducing infection. In this study, we present an overview of the currently used approaches of surface functionalization and modifications of BGs, along with discussing the biological outputs induced by these changes.

Tumor-targeted drug-loaded nanocarriers represent innovative and attractive tools for cancer therapy. Several magnetic nanoparticles (MNPs) were analyzed as potential tumor-targeted drug-loaded nanocarriers after functionalization with anti-Met oncogene (anti-Met/HGFR) monoclonal antibody (mAb) and doxorubicin (DOXO). Their cytocompatibility, stability, immunocompetence (immunoprecipitation), and their interactions with cancer cells in vitro (Perl&rsquo, s staining, confocal microscopy, cytotoxic assays: MTT, real time toxicity) and with tumors in vivo (Perl&rsquo, s staining) were evaluated. The simplest silica- and calcium-free mAb-loaded MNPs were the most cytocompatible, the most stable, and showed the best immunocompetence and specificity. These mAb-functionalized MNPs specifically interacted with the surface of Met/HGFR-positive cells, and not with Met/HGFR-negative cells, they were not internalized, but they discharged in the targeted cells DOXO, which reached the nucleus, exerting cytotoxicity. The presence of mAbs on DOXO-MNPs significantly increased their cytotoxicity on Met/HGFR-positive cells, while no such effect was detectable on Met/HGFR-negative cells. Bare MNPs were biocompatible in vivo, mAb presence on MNPs induced a better dispersion within the tumor mass when injected in situ in Met/HGFR-positive xenotumors in NOD/SCID-&gamma, null mice. These MNPs may represent a new and promising carrier for in vivo targeted drug delivery, in which applied gradient and alternating magnetic fields can enhance targeting and induce hyperthermia respectively.

In recent years, bioactive glasses gained increasing scientific interest in bone tissue engineering due to their capability to chemically bond with the host tissue and to induce osteogenesis. As a result, several efforts have been addressed to use bioactive glasses in the production of three-dimensional (3D) porous scaffolds for bone regeneration. In this work, we creatively combine typical concepts of porous glass processing with those of waste management and propose, for the first time, the use of bread as a new sacrificial template for the fabrication of bioactive scaffolds. Preliminary SEM investigations performed on stale bread from industrial wastes revealed a suitable morphology characterized by an open-cell 3D architecture, which is potentially able to allow tissue ingrowth and vascularization. Morphological features, mechanical performances and in vitro bioactivity tests were performed in order to evaluate the properties of these new &ldquo, sustainable&rdquo, scaffolds for bone replacement and regeneration. Scaffolds with total porosity ranging from 70 to 85 vol% and mechanical strength comparable to cancellous bone were obtained. Globular hydroxyapatite was observed to form on the surface of the scaffolds after just 48-h immersion in simulated body fluid. The results show great promise and suggest the possibility to use bread as an innovative and inexpensive template for the development of highly-sustainable bone tissue engineering approaches.

Bioactive materials, able to induce hydroxyapatite precipitation in contact with body fluids, are of great interest for their bone bonding capacity. . The aim of this paper is to compare bioactive materials with different surface features to verify the mechanisms of action and the relationship with kinetics and type of precipitated hydroxyapatite over time. Four different surface treatments for Ti/Ti6Al4V alloy and a bioactive glass were selected and a different mechanism of bioactivity is supposed for each of them. Apart from the conventional techniques (FESEM, XPS and EDX), less common characterizations (zeta potential measurements on solid surfaces and FTIR chemical imaging) were applied. The results suggest that the OH groups on the surface have several effects: the total number of the OH groups mainly affects hydrophilicity of surfaces, while the isoelectric points, surface charge and ions attraction mainly depend on OH acidic/basic strength. Kinetics of hydroxyapatite precipitation is faster when it involves a mechanism of ion exchange while it is slower when it is due to electrostatic effects . The electrostatic effect cooperates with ion exchange and it speeds up kinetics of hydroxyapatite precipitation. Different bioactive surfaces are able to differently induce precipitation of type A and B of hydroxyapatite, as well as different degrees of crystallinity and carbonation. STATEMENT OF SIGNIFICANCE: The bone is made of a ceramic phase (a specific type of hydroxyapatite), a network of collagen fibers and the biological tissue. A strong bond of an orthopedic or dental implant with the bone is achieved by bioactive materials where precipitation and growth of hydroxyapatite occurs on the implant surface starting from the ions in the physiological fluids. Several bioactive materials are already known and used, but their mechanism of action is not completely known and the type of precipitated hydroxyapatite not fully investigated. In this work, bioactive titanium and bioglass surfaces are compared through conventional and innovative methodologies. Different mechanisms of bioactivity are identified, with different kinetics and the materials are able to induce precipitation of different types of hydroxyapatite, with different degree of crystallinity and carbonation.

In this research work composite coatings made of alginate and 45S5 bioactive glass particles doped with B, Zn or Sr were synthesized by means of electrophoretic deposition and characterized from morphological, compositional, thermogravimetric, mechanical and electrochemical points of view. The developed coatings were also subjected to in vitro test in SBF solution to evaluate their ability to induce hydroxyapatite precipitation and cytocompatibility evaluation using human primary fibroblasts. The obtained results demonstrated a good homogeneity of the coatings, high adhesion and a protective behavior towards the substrate. The thermogravimetric analysis proved that the glass amount was constant before and after the deposition and all the investigated coatings promoted the deposition of hydroxyapatite but with different kinetics. Since the Zn containing coating showed the best bioactive behavior it was subjected to cytocompatibility test, which demonstrated, after an initial reduction of cell viability, a good cell proliferation and the production of collagen from the ECM. These findings suggest that the obtained coatings are promising materials to coat metallic prosthetic devices.

In this work, three commercial PMMA-based bone cements (high, medium and low viscosities) were enriched with a bioactive and Ag-containing glass to contemporaneously impart bioactive and antibacterial properties. For each formulation, the glass distribution in the polymeric matrix, the bioactivity in simulated body fluid, the silver release, the antibacterial effect and cytotoxicity were evaluated. Morphological and compositional characterizations, by means of scanning electron microscopy and energy-dispersive spectrometry, evidenced good glass dispersion in the polymeric matrix and its appreciable exposition on material surface for all composite cements. The different formulations did not entail the composite ability to induce hydroxyapatite precipitation on their surface (bioactivity) and to release silver ions. The silver release profile was comparable with the rate of infection development; moreover, antibacterial test (inhibition halo evaluation and count of colonies forming units) revealed a significant antibacterial effect towards S. aureus strain. Finally, cytotoxicity test, performed using continuous mouse fibroblast L-929, showed none cytotoxic effect of the multifunctional composite cements for all the polymeric matrix formulations.

Magnetite-containing glass-ceramics are promising bio-materials for replacing bone tissue after tumour resection. Thanks to their ferrimagnetic properties, they generate heat when subjected to an alternated magnetic field. In virtue of this they can be employed for the hyperthermic treatment of cancer. Moreover, grafting anti-cancer drugs onto their surface produces specific anti-neoplastic activity in these biomaterials. Gallic acid (GA) exhibits antiproliferative activity which renders it a promising candidate for anticancer applications. In the present paper, the reactivity of ferrimagnetic glass-ceramic SC-45 grafted with GA (SC-45+GA) was studied in terms of ROS release, rupture of the C–H bond of the formate molecule and Fenton reactivity by EPR/spin trapping in acellular systems. The ability of these materials to cause lipid peroxidation was assessed by UV–vis/TBA assay employing linoleic acid as a model of membrane lipid. The results, compared to those obtained with SC-45, showed that GA grafting (i) significantly enhanced the Fenton reactivity and (ii) restored the former reactivity of SC-45 towards both the C–H bond and linoleic acid which had been completely suppressed by prolonged contact with water. Fe 2+ centres at the surface are probably implicated. GA, acting as a pro-oxidant, reduces Fe 3+ to Fe 2+ by maintaining a supply of Fe 2+ at the surface of SC-45+GA.

Polyphenols are actually achieving an increasing interest due to their potential health benefits, such as antioxidant, anticancer, antibacterial and bone stimulation abilities. However their poor bioavailability and stability hamper an effective clinical application as therapeutic principles. The opportunity to couple these biomolecules with synthetic biomaterials, in order to obtain local delivery at the site of interest, improve their bioavailability and stability and combine their properties with the ones of the substrate, is a challenging opportunity for the biomedical research. A silica based bioactive glass, CEL2, has been successfully coupled with gallic acid and natural polyphenols extracted from red grape skins and green tea leaves. The effectiveness of grafting has been verified by means of XPS analyses and the Folin&Ciocalteu tests. In vitro bioactivity has been investigated by soaking in simulated body fluid (SBF). Surface modification after functionalization and early stage reactivity in SBF have been studied by means of zeta potential electrokinetic measurements in KCl and SBF. Finally the antioxidant properties of bare and modified bioactive glasses has been investigated by means of the evaluation of free radical scavenging activity by Electron Paramagnetic Resonance (EPR)/spin trapping technique after UV photolysis of H2O2 highlighting scavenging activity of the bioactive glass.

Discouraging bacterial colonization of ocular biomaterials and implants is a significant challenge in ophthalmology as infections often lead to the need for secondary surgery, with associated risks and additional stress to patients. In this work we demonstrate for the first time the feasibility of an innovative antibacterial ocular prosthesis produced by depositing a silver nanocluster/silica composite layer on the poly(methyl methacrylate) implant surface via radio-frequency sputtering. Tape test performed according to relevant ASTM standard provided a preliminary evidence of the mechanical stability and good adhesion of the coating to the substrate (absence of macroscopic damage after tape removal). Coating integrity was maintained after prolonged soaking in aqueous medium (1 month). The antibacterial effect of the coating, associated to silver ion release upon contact with aqueous fluid, was confirmed by the in vitro formation of a 5-mm inhibition halo test against Staphylococcus aureus that is one of the most common bacteria involved in ocular infections. The approach proposed in the present study for facing implant-related ocular infections can have a significant impact in the field of ophthalmic biomaterials, suggesting a valuable alternative to the administration of antibiotics that may become ineffective due to bacterial resistance.

The fight against cancer is an old challenge for mankind. Apart from surgery and chemotherapy, which are the most common treatments, use of radiation represents a promising, less invasive strategy that can be performed both from the outside or inside the body. The latter approach, also known as brachytherapy, relies on the use of implantable beta-emitting seeds or microspheres for killing cancer cells. A set of radioactive glasses have been developed for this purpose but their clinical use is still mainly limited to liver cancer. This review paper provides a picture of the biomedical glasses developed and experimented for brachytherapy so far, focusing the discussion on the production methods and current limitations of the available options to their diffusion in clinical practice. Highly-durable neutron-activatable glasses in the yttria-alumina-silica oxide system are typically preferred in order to avoid the potentially-dangerous release of radioisotopes, while the compositional design of degradable glass systems suitable for use in radiotherapy still remains a challenge and would deserve further investigation in the near future.

Bioactive glasses (BGs) are traditionally known to be able to bond to living bone and stimulate bone regeneration. The production of such materials in a mesoporous form allowed scientists to dramatically expand the versatility of oxide-based glass systems as well as their applications in biomedicine. These nanostructured materials, called mesoporous bioactive glasses (MBGs), not only exhibit an ultrafast mineralization rate but can be used as vehicles for the sustained delivery of drugs, which are hosted inside the mesopores, and therapeutic ions, which are released during material dissolution in contact with biological fluids. This review paper summarizes the main strategies for the preparation of MBGs, as well as their properties and applications in the biomedical field, with an emphasis on the methodological aspects and the promise of hierarchical systems with multiscale porosity.

Background:: Peri-prosthetic infections are characterized by high resistance to systemic antibiotic therapy. In this work, commercial PMMA-based bone cement has been loaded with a bioactive glass doped with silver ions, with the purpose to prepare composite bone cement containing a single inorganic phase with both bioactive and antibacterial properties, able to prevent bacterial contamination. Methods:: The glass distribution in the polymeric matrix, the composites radio-opacity, the bending strength and modulus, the morphology of the fracture surfaces, the bioactivity in Simulated Body Fluid (SBF) and the antibacterial effect were evaluated. The glass particles dispersion in the polymeric matrix and their exposition on the polymer surface have been assessed by morphological and compositional characterizations via Scanning Electron Microscopy (SEM) and Energy Dispersion Spectroscopy (EDS). Results:: The introduction of the silver-doped bioactive glass allowed imparting an intrinsic radio-opacity to the cement. The bending strength and modulus were influenced by the glass preparation, amount and grain-size. The polymeric matrix did not affect the composite ability to induce hydroxyapatite precipitation on its surface (bioactivity). Moreover, antibacterial test (inhibition halo evaluation) revealed a significant antibacterial effect toward S. aureus, Bacillus, E. coli and C. albicans strains. Conclusion:: The obtained results motivate further investigations and future in vivo tests.

Multifunctional scaffolds were prepared by foaming Fe-containing sols according to a composition-optimized approach. These foams exhibited high specific surface area (16–80 m2/g) and hierarchical porosity from the macro- (50–600 µm) to the meso-scale (4–20 nm). The effects of iron content on the textural properties and in vitro bioactivity were investigated. It was observed that the increase of iron content involved a decrease of specific surface and mesopore size. Interestingly, an excellent apatite-forming ability was observed regardless of the material composition. The potential osteoconductivity of these bioactive foams, coupled with their ferrimagnetic properties, open new perspectives as regards the hyperthermia-assisted treatment and regeneration of osseous defects caused by bone cancer.

In recent decades the applications of nanotechnology in the biomedical field have attracted a lot of attention. Magnetic and gold nanoparticles (MNPs and GNPs) are now of interest as selective tools for tumour treatment, due to their unique properties and biocompatibility. In this paper, superparamagnetic iron oxide nanoparticles (MNPs) decorated with gold nanoparticles (GNPs) have been prepared by means of an innovative synthesis process using tannic acid as the reducing agent. The as-obtained nanoplatforms were characterized in terms of size, morphology, structure, composition, magnetic response and plasmonic properties. The results revealed that hybrid nanoplatforms (magnetoplasmonic nanoparticles, MPNPs) composed of a magnetic core and an external GNP decoration, acting in synergy, have been developed. Biological tests were also performed on both healthy cells and cancer cells exposed to different nanoparticle concentrations, upon laser irradiation. GNPs grafted onto the surface of MNPs revealed the ability to convert the received light into thermal energy, which was selective in its detrimental effect on cancer cells.

Magnetite-based nanoparticles (NPs) were synthesized by co-precipitation process and coated with a thin layer of silica, eventually doped with calcium, by a modified Stober method. The potential bioactive behavior of NPs was investigated by dipping samples in simulated body fluid (SBF) and analyzing them with Field-Emission Scanning Electron Microscope (FESEM) equipped with Energy Dispersive Spectroscopy (EDS). Silica-coated NPs displayed evidence of HAp grown on their surface and were then used as a filler for polymethyl methacrylate (PMMA)-based bone cement to impart bioactive and magnetic properties. The influence of the amount of magnetic NPs and the cement mixing method (manual or mechanical) were estimated in terms of NPs dispersion, compressive strength and bioactive behavior. The obtained data evidenced that both the NPs amount and the mixing method influenced the strength of the composites. A delay in the bioactivity was observed for manual mixed cement; moreover, mechanically mixed composites containing a low amount of NPs showed superparamagnetic behavior. These results suggest that the investigated composite bone cements are promising materials for the treatment of bone tumors and associated complications.

Polymethyl methacrylate (PMMA)-based bone cement is a biomaterial that has been used over the last 50 years to stabilize hip and knee implants or as a bone filler. Although PMMA-based bone cement is widely used and allows a fast-primary fixation to the bone, it does not guarantee a mechanically and biologically stable interface with bone, and most of all it is prone to bacteria adhesion and infection development. In the 1970s, antibiotic-loaded bone cements were introduced to reduce the infection rate in arthroplasty; however, the efficiency of antibiotic-containing bone cement is still a debated issue. For these reasons, in recent years, the scientific community has investigated new approaches to impart antibacterial properties to PMMA bone cement. The aim of this review is to summarize the current status regarding antibiotic-loaded PMMA-based bone cements, fill the gap regarding the lack of data on antibacterial bone cement, and explore the progress of antibacterial bone cement formulations, focusing attention on the new perspectives. In particular, this review highlights the innovative study of composite bone cements containing inorganic antibacterial and bioactive phases, which are a fascinating alternative that can impart both osteointegration and antibacterial properties to PMMA-based bone cement.

Borosilicate bioactive glasses are attracting an increasing interest due to their good hot forming ability, low crystallization tendency and high bioactivity. Surface functionalization of bioactive glasses is a versatile tool for modulation of their properties and consequently of their biological response and it is still an unexplored topic in the case of borosilicate glasses. The possibility to graft 3-aminopropyltriethoxysilane (APTES) to various borosilicate bioactive glasses have been investigated in the present research work. Glasses were produced by melting and completely characterized (SEM-EDS, density, FTIR-ATR, Raman, NMR, zeta potential and reactivity in SBF and TRIS/HCl). Then, APTES was grafted to the surface of the glasses and its presence was verified by means of XPS, contact angle and zeta potential measurements. This study has shown the possibility to silanize borosilicate bioactive glasses for the first time, however, this silanization protocol does not induce the formation of a continuous coating on the glass surface.

Bacterial contamination and bone tissue overgrowth are currently the main issues for temporary fixation devices. The aim of this research is the development of innovative inorganic coatings able to reduce bacterial adhesion and bone tissue overgrowth without hampering cytocompatibility. 316L stainless-steel, Titanium grade4 and Titanium grade5 were selected as substrates, as currently used in temporary fixation devices. Starting from previous results on silica, alumina and zirconia were selected as coating matrices, according to their higher chemical stability, reduced bacterial adhesion and possible reduction of tissue overgrowth. Coatings were produced by co-sputtering. Coating adhesion was evaluated by tape test. Samples were immersed in ultrapure water up to 28 days to investigate silver release and chemical stability in fluids. Surface roughness was measured by contact profilometry. Surface wettability was determined by contact angle measurements and antibacterial activity was studied against antibiotic resistant S aureus. The research demonstrates the possibility to obtain coatings with roughness lower than the critical threshold for the increase of bacterial adhesion (0.2 µm) and optimal mechanical adhesion to metallic substrates. Coating chemical stability in water is strongly affected by the coating matrix composition. Silver release can be tailored to obtain antibacterial and biocompatible surfaces.

Nowadays, bioactive glasses (BGs) are mainly used to improve and support the healing process of osseous defects deriving from traumatic events, tumor removal, congenital pathologies, implant revisions, or infections. In the past, several approaches have been proposed in the replacement of extensive bone defects, each one with its own advantages and drawbacks. As a result, the need for synthetic bone grafts is still a remarkable clinical challenge since more than 1 million bone-graft surgical operations are annually performed worldwide. Moreover, recent studies show the effectiveness of BGs in the regeneration of soft tissues, too. Often, surgical criteria do not match the engineering ones and, thus, a compromise is required for getting closer to an ideal outcome in terms of good regeneration, mechanical support, and biocompatibility in contact with living tissues. The aim of the present review is providing a general overview of BGs, with particular reference to their use in clinics over the last decades and the latest synthesis/processing methods. Recent advances in the use of BGs in tissue engineering are outlined, where the use of porous scaffolds is gaining growing importance thanks to the new possibilities given by technological progress extended to both manufacturing processes and functionalization techniques.

A chemically-treated titanium alloy (Ti6Al4V) surface, able to induce hydroxyapatite precipitation from body fluids (inorganic mineralization activity), was functionalized with a polyphenolic extract from green tea (tea polyphenols, TPH). Considering that green tea polyphenols have stimulating effects on bone forming cells (biological mineralization), the aim was to test their osteoinductive behavior due to co-operation of inorganic and biological mineralization on mesenchymal stem cells KUSA A1. The functionalized surfaces were characterized by using the Folin&ndash, Ciocalteu method and X-ray photoelectron spectroscopy to confirm the successful outcome of the functionalization process. Two cell cultures of mesenchymal stem cells, KUSA A1 were performed, with or without osteoinductive factors. The cells and surfaces were characterized for monitoring cell viability and hydroxyapatite production: Fourier Transform Infrared Spectroscopy and Raman spectroscopy analyses showed deposition of hydroxyapatite and collagen due to the cell activity, highlighting differentiation of KUSA A1 into osteoblasts. A higher production of extracellular matrix was highlighted on the functionalized samples by laser microscope and the fluorescence images showed higher viability of cells and greater presence of osteocalcin in these samples. These results highlight the ability of polyphenols to improve cell differentiation and to stimulate biological mineralization, showing that surface functionalization of metal implants could be a promising way to improve osteointegrability.

To promote osteointegration and simultaneously limit bacterial contamination without using antibiotics, we designed innovative composite cements containing copper (Cu)-doped bioactive glass powders. Cu-doped glass powders were produced by a melt and quenching process, followed by an ion-exchange process in a Cu salt aqueous solution. Cu-doped glass was incorporated into commercial polymethyl methacrylate (PMMA)-based cements with different viscosities. The realized composites were characterized in terms of morphology, composition, leaching ability, bioactivity, mechanical, and antibacterial properties. Glass powders appeared well distributed and exposed on the PMMA surface. Composite cements showed good bioactivity, evidencing hydroxyapatite precipitation on the sample surfaces after seven days of immersion in simulated body fluid. The leaching test demonstrated that composite cements released a significant amount of copper, with a noticeable antibacterial effect toward Staphylococcus epidermidis strain. Thus, the proposed materials represent an innovative and multifunctional tool for orthopedic prostheses fixation, temporary prostheses, and spinal surgery.

This work deals with the synthesis and characterization of novel Fe-containing sol-gel materials obtained by modifying the composition of a binary SiO2-CaO parent glass with the addition of Fe2O3. The effect of different processing conditions (calcination in air vs. argon flowing) on the formation of magnetic crystalline phases was investigated. The produced materials were analyzed from thermal (hot-stage microscopy, differential thermal analysis, and differential thermal calorimetry) and microstructural (X-ray diffraction) viewpoints to assess both the behavior upon heating and the development of crystalline phases. N2 adsorption–desorption measurements allowed determining that these materials have high surface area (40–120 m2/g) and mesoporous texture with mesopore size in the range of 18 to 30 nm. It was assessed that the magnetic properties can actually be tailored by controlling the Fe content and the environmental conditions (oxidant vs. inert atmosphere) during calcination. The glasses and glass-ceramics developed in this work show promise for applications in bone tissue healing which require the use of biocompatible magnetic implants able to elicit therapeutic actions, such as hyperthermia for bone cancer treatment.

Multicomponent silicate glasses and their corresponding glass-ceramic derivatives were prepared and tested for potential applications in dentistry. The glasses were produced via a melting-quenching process, ground and sieved to obtain fine-grained powders that were pressed in the form of small cylinders and thermally treated to obtain sintered glass-ceramic samples. X-ray diffraction investigations were carried out on the materials before and after sintering to detect the presence of crystalline phases. Thermal analyses, mechanical characterizations (assessment of bending strength, Young’s modulus, Vickers hardness, fracture toughness), and in vitro bioactivity tests in simulated body fluid were performed. On the basis of the acquired results, different potential applications in the dental field were discussed for the proposed glass-ceramics. The use of such materials can be suggested for either restorative dentistry or dental implantology, mainly depending on their peculiar bioactive and mechanical properties. At the end of the work, the feasibility of a novel full-ceramic bilayered implant was explored and discussed. This implant, comprising a highly bioactive layer expected to promote osteointegration and another one mimicking the features of tooth enamel, can have an interesting potential for whole tooth substitution.

In this work silica-based bioactive glass powders were doped with Cu++ ions by means of ion-exchange process and subsequently they were exposed to different chemical (tannic acid, ascorbic acid and NaOH) and physical processes (UV irradiation, thermal treatment in air or argon atmosphere) to promote the in situ reduction of Cu++ ions to Cu+ or Cu0. The obtained glasses were investigated by means of structural (X-Ray diffraction – XRD), morphological and compositional analyses (scanning-transmission electron microscopy equipped with energy dispersive spectroscopy (FESEM/STEM-EDS); moreover, glasses were subjected to in vitro bioactivity test in simulated body fluid up to 14 days to investigate the influence of the performed chemical and physical treatments on glass bioactivity. At the end of incubation time glasses were analyzed by means of FESEM-EDS and Fourier transformation infrared spectroscopy (FT-IR). The obtained results evidenced that, in general, the chemical treatments are useful to induce the formation of Cu0, while thermal treatment induce the nucleation of CuO (in air) or Cu2O (in argon). All samples maintained a bioactive behavior. At least, preliminary antibacterial effect evaluation by inhibition halo test evidenced that samples containing free Cu++ ions or Cu0 nanoparticles possess the best antibacterial effect.

Additive manufacturing of bioactive glasses has recently attracted high interest in the field of regenerative medicine as a versatile class of fabrication methods to process bone substitute materials. In this study, melt-derived glass particles from the SiO2-P2O5-CaO-MgO-Na2O-K2O system were used to fabricate bioactive scaffolds with graded porosity by robocasting. A printable ink made of glass powder and Pluronic F-127 (binder) was extruded into a grid-like three-dimensional structure with bimodal porosity, i.e., the inner part of the scaffold had macropores with smaller size compared to the periphery. The crystallization behavior of the glass powder was studied by hot-stage microscopy, differential thermal analysis, and X-ray diffraction, the scaffolds were sintered at a temperature below the onset of crystallization so that amorphous structures could be obtained. Scaffold architecture was investigated by scanning electron microscopy and microtomographic analysis that allowed quantifying the microstructural parameters. In vitro tests in Kokubo&rsquo, s simulated body fluid (SBF) confirmed the apatite-forming ability (i.e., bioactivity) of the scaffolds. The compressive strength was found to slightly decrease during immersion in SBF up to 4 weeks but still remained comparable to that of human cancellous bone. The pH and concentration of released ions in SBF were also measured at each time point. Taken together, these results (favorable porosity, mechanical strength, and in vitro bioactivity) show great promise for the potential application of these robocast scaffolds in bone defect repair.

Nanomaterials conjugated or complexed with biological moieties such as antibodies, polymers or peptides appear to be suitable not only for drug delivery but also for specific cancer treatment. Here, biocompatible iron oxide magnetic nanoparticles (MNPs) with or without a silica shell coupled with lentiviral vectors (LVs) are proposed as a combined therapeutic approach to specifically target gene expression in a cancer mouse model. Initially, four different MNPs were synthesized and their physical properties were characterized to establish and discriminate their behaviors. MNPs and LVs strictly interacted and transduced cells in vitro as well as in vivo , with no toxicity or inflammatory responses. By injecting LV-MNPs complexes intravenously, green fluorescent protein (GFP) resulted in a sustained long-term expression. Furthermore, by applying a magnetic field on the abdomen of intravenous injected mice, GFP positive cells increased in livers and spleens. In liver, LV-MNPs were able to target both hepatocytes and non-parenchymal cells, while in a mouse model with a grafted tumor, intra-tumor LV-MNPs injection and magnetic plaque application next to the tumor demonstrated the efficient uptake of LV-MNPs complexes with high number of transduced cells and iron accumulation in the tumor site. More important, LV-MNPs with the application of the magnetic plaque spread in all the tumor parenchyma and dissemination through the body was prevented confirming the efficient uptake of LV-MNPs complexes in the tumor. Thus, these LV-MNPs complexes could be used as multifunctional and efficient tools to selectively induce transgene expression in solid tumor for therapeutic purposes. Statement of Significance Our study describes a novel approach of combining magnetic properties of nanomaterials with gene therapy. Magnetic nanoparticles (MNPs) coated with or without a silica shell coupled with lentiviral vectors (LVs) were used as vehicle to target biological active molecules in a mouse cancer model. After in situ injection, the presence of MNP under the magnetic field improve the vector distribution in the tumor mass and after systemic administration, the application of the magnetic field favor targeting of specific organs for LV transduction and specifically can direct LV in specific cells (or avoiding them). Thus, our findings suggest that LV-MNPs complexes could be used as multifunctional and efficient tools to selectively induce transgene expression in solid tumor for therapeutic purposes.