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Calcium phosphates (CaPs) are biocompatible and biodegradable materials showing a great promise in bone regeneration as good alternative to the use of auto- and allografts to guide and support tissue regeneration in critically-sized bone defects. This can be certainly attributed to their similarity to the mineral phase of natural bone. Among CaPs, hydroxyapatite (HA) deserves a special attention as it, actually is the main inorganic component of bone tissue. This review offers a comprehensive overview of past and current trends in the use of HA as grafting material, with a focus on manufacturing strategies and their effect on the mechanical properties of the final products. Recent advances in materials processing allowed the production of HA-based grafts in different forms, thus meeting the requirements for a range of clinical applications and achieving enthusiastic results both in vitro and in vivo. Furthermore, the growing interest in the optimization of three-dimensional (3D) porous grafts, mimicking the trabecular architecture of human bone, has opened up new challenges in the development of bone-like scaffolds showing suitable mechanical performances for potential use in load bearing anatomical sites.

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

In vitro and in vivo studies are fundamental steps in the characterization of new implantable materials to preliminarily assess their biological response. The present study reports the in vitro and in vivo characterizations of a novel experimental silicate bioactive glass (BG) (47.5B, 47.5SiO2-10Na2O-10K2O-10MgO-20CaO-2.5P2O5 mol.%). Cytocompatibility tests were performed using human mature osteoblasts (U2OS), human mesenchymal stem cells (hMSCs) and human endothelial cells (EA.hy926). The release of the early osteogenic alkaline phosphatase (ALP) marker suggested strong pro-osteogenic properties, as the amount was comparable between hMSCs cultivated onto BG surface and cells cultivated onto polystyrene control. Similarly, real-time PCR revealed that the osteogenic collagen I gene was overexpressed in cells cultivated onto BG surface without biochemical induction. Acute toxicity tests for the determination of the median lethal dose (LD50) allowed classifying the analyzed material as a slightly toxic substance with LD50 = 4522 ± 248 mg/kg. A statistically significant difference in bone formation was observed in vivo through comparing the control (untreated) group and the experimental one, proving a clear osteogenic effect induced by the implantation at the defect site. Complete resorption of 47.5B powder was observed after only 3 months in favor of newly formed tissue, thus confirming the high osteostimulatory potential of 47.5B glass.

An extract of polyphenols was obtained from organic red grape pomace, chemically analyzed, and used for functionalization of two bioactive glasses and porous hy- droxyapatite. Functionalization is effective on hydroxyapatite and the bioactive glass with higher surface reactivity with a different grafting mechanism. Grafting does not inhibit redox and radical scavenging activity of polyphenols. The grafted polyphenols make a continuous layer with an almost complete surface coverage. Polyphenols are released with different kinetics according to the mechanism of grafting and maintain their redox activity. A homogeneous thin layer of polyphenols is still firmly grafted on both substrates after 28days of soaking and it still maintains radical scavenging activity. The functionalized samples can be sterilized by gamma irradiation.

The invention of bioactive glasses has undoubtedly represented an important watershed in the history of biomedicine, innovatively revolutionizing the key concept of biomaterials. Although 50 years have passed since the first bioactive glass (45S5 Bioglass®), these materials still continue to inspire numerous generations of researchers all over the world, attracted by the promise of numerous possible fields of investigations given by the versatility of glass manufacturing and processing strategies. This allows obtaining final clinical products that are incredibly diverse in terms of chemical characteristics, shape and texture and, therefore, adaptable to different therapeutic needs. The possibility to tune textural properties and degradation rates, perform high-temperature sintering processes without or minimally altering the original properties of the glass, as well as the facile introduction of therapeutically active ions within the composition and the easy surface functionalization led, over year, to the development of multiple pruducts to be used in various clinical fields, including the regeneration of both hard and soft tissues, bacterial/viral infection treatments and development of antitumoral strategies. This chapter opens a wide window on the world of bioactive glasses, starting with the description of their peculiar chemical properties, discussed in relation to the most commonly used manufacturing processes to obtain glass monoliths or particles. Then, an overview on the most common applications of BG-based products will be provided, paying particular attention to porous scaffolds for bone tissue engineering, bioactive coatings, antibacterial glasses and surface functionalization. In conclusion, a comprehensive overview on clinical applications updated to the state of the art will be provided.

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.

Advanced bone tissue engineering approaches rely on implanting synthetic grafts for the management of mid to large bone defects in order to overcome the common limitations associated with the use of transplant materials. Bioceramics are especially effective due to their versatile functional properties and processing methods. This chapter provides a picture of ceramic scaffolds for bone tissue engineering, focusing on additive manufacturing technologies and, specifically, the emerging method of digital light processing. The functional and structural complexity of natural bone makes the design of scaffolds a complex challenge as their chemical, structural and functional properties have to meet very specific requirements, e.g. adequate support properties, bone-bonding capability and a macro- and microporous structure to promote cell colonization and vascularization. Many fabrication techniques are currently available for the production of porous artificial biomaterials. Among them, the class of additive manufacturing technologies is one of the most promising methods for the development of mechanically competent and structurally highly defined scaffolds with tailored properties for bone tissue engineering applications.

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.

Copper-containing ferrimagnetic glass-ceramic with the following composition: 24.7% SiO2-8.5% CaO-13.5% Na2O-3.3% P2O5-31% Fe2O3-14% FeO–5CuO (wt%) was synthesized by means melt and quenching process both in powder and bulk form. The obtained samples were characterized and compared by means morphological, compositional and structural analyses. The magnetic properties and the ability to release heat were also investigated together with the antimicrobial properties towards S. aureus strain. The obtained results showed that copper introduction and the annealing process influenced the nucleation of crystalline phases; in particular the samples produced in powder form evidenced a low amount of magnetite and thus a reduced hysteresis area and ability to produce heat when exposed to an alternating magnetic field. While Cu-containing samples in the bulk form maintained the magnetic and calorimetric properties of pristine glass-ceramic. Preliminary evaluation of antibacterial properties demonstrated Cu-doped samples were not able to reduce the bacterial proliferation and thus the need to optimize the copper introduction process.

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.

Since the discovery of 45S5 Bioglass® by Larry Hench, bioactive glasses have been widely studied as bone substitute materials and, in more recent years, have also shown great promise for producing three-dimensional scaffolds. The development of additive manufacturing techniques and their application in bone tissue engineering allows the design and fabrication of complex structures with controlled porosity. However, achieving strong and mechanically-reliable bioactive glass scaffolds is still a great challenge. Furthermore, there is a relative paucity of studies reporting an exhaustive assessment of other mechanical properties than compressive strength of glass-derived scaffolds. This research work aimed at determining key mechanical properties of silicate SiO2-Na2O-K2OMgO-CaO-P2O5 glass scaffolds fabricated by robocasting and exhibiting a porosity gradient. When tested in compression, these scaffolds had a strength of 6 MPa, a Young’s modulus around 340 MPa, a fracture energy of 93 kJ/m3 and a Weibull modulus of 3, which provides a quantification of the scaffold reliability and reproducibility. Robocasting was a suitable manufacturing method to obtain structures with favorable porosity and mechanical properties comparable to those of the human cancellous bone, which is fundamental regarding osteointegration of bone implants.

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.

Biomolecules and extracts from natural products are gaining increasing interest due to their beneficial properties for human health, low toxicity, environmental compatibility and sustainability. In this work, keratin, chitosan and peppermint essential oil have been used for the preparation of coatings on titanium substrates for biomedical implants or devices. All these coatings were obtained from local natural products or byproducts: keratin from discarded wool, chitosan from shrimps shells and peppermint essential oils from a local production. This approach supports a sustainable use of the resources and the sustainment of local economies with transformation of byproducts in high added values products. Keratin was chosen for its ability to stimulate soft tissue adhesion and to be easily doped with metal ions in order to confer even antibacterial activity. Keratin coatings were realized as electrospun oriented/random submicrometric fibres or continuous films. Chitosan was selected for its anti-inflammatory and antibacterial properties. Continuous coatings were obtained with different grafting strategies (direct grafting, tresyl chloride activation or polydopamine addition). Peppermint essential oil was chosen for its antibacterial activity and used for the obtainment of continuous coatings based on the self polymerizing ability of terpenes. The coatings were characterized by means of SEM-EDS, FTIR, zeta potential, wettability, tape and scratch tests, cell and bacteria cultures. Coatings were successfully obtained for all the considered natural substances. Good adhesion to titanium substrates was reached through the optimization of the surface preparation and grafting process. All the coatings were chemically stable in water and the continuous coating were mechanically resistant and protective for the metallic substrate. The keratin coatings were hydrophilic while mint oil and chitosan coatings were hydrophobic. At physiological pH, keratin and mint oil coatings were negatively charged while chitosan ones were positively charged. The oriented keratin fibres were able to drive fibroblast alignment. Ag-doped keratin fibres and mint coating showed antibacterial properties.

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.

The crystallization process of a bioactive silicate glass with 47.5SiO2-10Na2O-10K2O-10MgO-20CaO-2.5P2O5 molar composition was investigated by using nonisothermal differential t hermal a nalysis (DTA). T he DTA plots recorded at different heating rates exhibited a single crystallization peak. The activation energy for crystallization was estimated by applying the equations proposed by Kissinger and Matusita-Sakka. The Johnson-Mehl-Avrami exponent (n) was assessed by using the Ozawa and Augis-Bennett methods. The analyses suggest that a surface crystallization mechanism with one-dimensional crystal growth is predominant. The activation energy for viscous flow was also assessed (176 kJ/mol) and was found lower than the activation energy for crystallization (271 kJ/mol). This confirms the stability of 47.5B against crystallization and its good sinterability, which is a highly attractive feature for producing glass products of biomedical interest, such as bioactive porous scaffolds for bone repair.