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The introduction of additive manufacturing technologies in the field of biomaterials science has opened new horizons for regenerative medicine. In this work, we pushed the potential of vat polymerization to the limit for fabricating ultra-porous bioactive SiO2-CaO-MgO-P2O5-CaF2-Na2O glass scaffolds with bone-like architectural characteristics. The tomographic reconstruction of an open-cell foam was used as input file to the printing system and reliably reproduced in all its exquisite details, as assessed by morphological analyses of sintered scaffolds (thickness of single struts 35 μm, exceptionally high porosity around 94 vol%, most pores with size from 500 to 900 μm). Immersion studies in simulated body fluid (SBF) revealed the apatite-forming ability (i.e., in vitro bioactivity) of the scaffolds, the surface of which started being coated by calcium phosphate after just 3 days from the beginning of the experiments. Taken together, these results show great promise for application of such scaffolds in bone defect repair.

Additive manufacturing technologies collectively refer to a set of layer-wise deposition methods that typically rely on CAD-CAM approaches for obtaining products with a complex shape/geometry and high precision and reliability. If the additive manufacturing of polymers is relatively easy and scalable due to the low temperatures needed to obtain processable inks, using similar technologies to fabricate ceramic products is indeed more challenging and expensive but, on the other hand, allows for obtaining high-quality results that would not be achievable through conventional methods. Furthermore, the implementation of additive manufacturing allows for the addressing of some important concerns related to the environment and sustainability, including the minimization of resource depletion and waste production/disposal. Specifically, additive manufacturing technologies can provide improvements in energy consumption and production costs, besides obtaining less waste material and less CO2 emissions, which are all key points in the context of the circular economy. After providing an overview of the additive manufacturing methods which are specifically applied to ceramics, this review presents the sustainability elements of these processing strategies, with a focus on both current and future benefits. The paucity of specific available studies in the literature—which are included and discussed in this review—suggests that the research on additive manufacturing sustainability in the field of ceramic materials is in the preliminary stage and that more relevant work still deserves to be carried out in the future to explore this fascinating field at the boundary among ceramics science/technology, production engineering and waste management.

Abstract This study focuses on the finite element simulation and micromechanical characterization of bioactive glass-ceramic scaffolds using Computed micro Tomography ( $$\upmu$$ μ CT) imaging. The main purpose of this work is to quantify the effect of sintering temperature on the morphometry and mechanical performance of the scaffolds. In particular, the scaffolds were produced using a novel bioactive glass material (47.5B) through foam replication, applying six different sintering temperatures. Through $$\upmu$$ μ CT imaging, detailed three-dimensional images of the scaffold’s internal structure are obtained, enabling the extraction of important geometric features and how these features change with sintering temperature. A finite element model is then developed based on the $$\upmu$$ μ CT images to simulate the fracture process under uniaxial compression loading. The model incorporates scaffold heterogeneity and material properties—also depending on sintering temperature—to capture the mechanical response, including crack initiation, propagation, and failure. Scaffolds sintered at temperatures equal to or higher than 700 $$^{\circ }$$ ∘ C exhibit two-scale porosity, with micro and macro pores. Finite element analyses revealed that the dual porosity significantly affects fracture mechanisms, as micro-pores attract cracks and weaken strength. Interestingly, scaffolds sintered at high temperatures, the overall strength of which is higher due to greater intrinsic strength, showed lower normalized strength compared to low-temperature scaffolds. By using a combined strategy of finite element simulation and $$\upmu$$ μ CT-based characterization, bioactive glass-ceramic scaffolds can be optimized for bone tissue engineering applications by learning more about their micromechanical characteristics and fracture response.

Bioactive glasses in the CaO–MgO–Na2O–P2O5–SiO2–CaF2 system are highly promising materials for bone and dental restorative applications. Furthermore, if thermally treated, they can crystallize into diopside–fluorapatite–wollastonite glass-ceramics (GCs), which exhibit appealing properties in terms of mechanical behaviour and overall bone-regenerative potential. In this review, we describe and critically discuss the genesis, development, properties and applications of bioactive glass “1d” and its relevant GC derivative products, which can be considered a good example of success cases in this class of SiO2/CaO-based biocompatible materials. Bioactive glass 1d can be produced by melt-quenching in the form of powder or monolithic pieces, and was also used to prepare injectable pastes and three-dimensional porous scaffolds. Over the past 15 years, it was investigated by the authors of this article in a number of in vitro, in vivo (with animals) and clinical studies, proving to be a great option for hard tissue engineering applications.

This review outlines the state of the art, processing techniques, and mechanical testing methods of zirconia (ZrO2)-based composites reinforced by carbon nanotubes (CNTs). The use of CNTs as a secondary phase in a zirconia matrix is motivated by their outstanding crack self-healing ability, the possibility to tailor the desired nano-structural properties, and their exceptional wear behavior. Therefore, a detailed investigation into CNT features has been provided. The debate of using the different Vickers indentation fracture toughness equations to estimate the resistance of crack propagation was critically reviewed according to crack characteristics. Finally, this review particularly highlights the exceptional role of ZrO2-based composites as a promising material owing to their outstanding tribo-mechanical properties.

Tocopherols are fat soluble substances with antioxidant properties. The α-Tocopherol (T) is the major form of Tocopherols and can decrease the risk of cancer. F127-based and Lignin-based oil-in-water microemulsions seem to increase the bioavailability of T and cause better release of this therapeutic agent. Thus, T-loaded microemulsions were designed by means of density functional theory (DFT) and semi-empirical methods. Atoms in molecules (AIM), natural bond orbital (NBO) analyses, localized molecular orbital energy decomposition analysis (LMO-EDA), and density of states plots were employed to explore the effective factors on the strength of the interactions between surfactants and T. Results indicate that F127-T complexes are more stable than Lignin-T ones. Furthermore, the stable release of T in microemulsions is due to the electrostatic interactions between surfactants and T. Formation of hydrogen bond (HB) interactions between surfactants and T stabilizes the microemulsion system. These interplays are suggested to take part in the better function of T in microemulsions compared to free T. The semi-empirical study reveals that the heats of formation (ΔHf values) of the F127-T complexes are less negative than those for the Lignin-T ones.

3D bioprinting techniques have emerged as a flexible tool in tissue engineering and regenerative medicine to fabricate or pattern functional 3D bio-structures with precise geometric designs, bridging the divergence between engineered and natural tissue constructs. A significantly increasing development has been achieved in understanding the relationship between the 3D-printing process and the structures, properties, and applications of the objects created. The ongoing advancement of novel biomaterial inks has enabled manufacturing of models and in vitro implants capable of achieving some level of success in preclinical trials. Remarkable progress in cell biology and biology-inspired computational design has assisted in achieving the latest milestone with planned tissue- or organ-like constructs having specific levels of functionality. However, biofabricated constructs still have a long way to go before reaching clinics. This review presents a picture of 3D bioprinting in the context of tissue engineering and regenerative medicine, with focus on biomaterials-related and design-centred aspects. Biomedical applications are described in detail in relation to major tissues or organs considered in the human body. Current technical limitations, challenges, future prospects and improvements are critically outlined and discussed.

Glass-ceramics (GCs) are polycrystalline materials produced from parent glasses by the controlled crystallization that results in crystalline phase(s) embedded in a residual amorphous matrix. Typically, GCs are produced by a conventional glass route with subsequent crystallization for which two heat treatments are usually applied, the former to generate nuclei and the latter being a crystal growth stage. Alternatively, another technically viable route for manufacturing GCs involves sintering of glass-powder compacts followed by crystallization (sinter-crystallization).Wollastonite-containing GCs from the CaO–Al2O3–SiO2 and CaO–MgO–SiO2 systems find a wide variety of uses in different technological fields, including construction, architecture, medical and high-tech fields. For example, a special type of wollastonite-containing GC marketed under the name of Neoparies®, which is stronger and lighter than natural stone, features high resistance to weathering/chemical attack and is manufactured on a large scale for construction and architectural applications. In the biomedical field, the well-known Cerabone® products have been used in bone-contact applications for many years.The main goal of this brief review is to provide a critical analysis of the experimental trials focusing on the synthesis of wollastonite-containing GC materials and to discuss the various fields of their application. Constitution of phase diagram of CaO–Al2O3–SiO2 and CaO–MgO–SiO2 systems are comprehensively discussed with connection to melt crystallization path and crystalline phase formation. Furthermore, special emphasis will be given to the production of wollastonite-containing GCs for construction and architectural purposes from natural raw materials and wastes, as well as to the recent advancement in developing wollastonite-containing GC biomaterials for bone repair.

A rapidly developing area of ceramic science and technology involves research on the interaction between implanted biomaterials and the human body. Over the past half century, the use of bioceramics has revolutionized the surgical treatment of various diseases that primarily affect bone, thus contributing to significantly improving the quality of life of rehabilitated patients. Calcium phosphates, bioactive glasses and glass-ceramics are mostly used in tissue engineering applications where bone regeneration is the major goal, while stronger but almost inert biocompatible ceramics such as alumina and alumina/zirconia composites are preferable in joint prostheses. Over the last few years, non-oxide ceramics—primarily silicon nitride, silicon carbide and diamond-like coatings—have been proposed as new options in orthopaedics in order to overcome some tribological and biomechanical limitations of existing commercial products, yielding very promising results. This review is specifically addressed to these relatively less popular, non-oxide biomaterials for bone applications, highlighting their potential advantages and critical aspects deserving further research in the future. Special focus is also given to the use of non-oxide ceramics in the manufacturing of the acetabular cup, which is the most critical component of hip joint prostheses.

As a major global cause of liver disease, non-alcoholic fatty liver disease (NAFLD) is characterized by excessive hepatocellular accumulation of lipids in the liver, elevated levels of hepatic enzymes, and fibrotic evidence. The primary therapies for NAFLD are changing lifestyle or managing comorbid-associated diseases. Lately, nanotechnology has revolutionized the art of nanostructure synthesis for disease imaging, diagnosis, and treatment. Loading drugs into nanocarriers has been established as a promising strategy to extend their circulating time, particularly in treating NAFLD. In addition, considering a master modulator of adipogenesis and lysosomal biogenesis and function, designing novel nanostructures for biomedical applications requires using biodegradable materials. Various nanostructures, including inorganic nanoparticles (NPs), organic-based NPs, metallic nanocarriers, biodegradable polymeric nanocarriers, polymer-hybrid nanocarriers, and lipid-based nanocarriers have been designed for NAFLD treatment, which significantly affected serum glucose/lipid levels and liver function indices. NPs modified with polymers, bimetallic NPs, and superparamagnetic NPs have been used to design sensitive nanosensors to measure NAFLD-related biomarkers. However, certain limitations are associated with their use as diagnostic agents. The purpose of this review article is to shed light on the recent advancements in the field of nanomedicine for the early diagnosis, treatment, and prognosis of this progressive liver disease.

This study explores the feasibility of bioactive glass scaffolds by using a stereolithographic technology (digital light processing-based vat photopolymerization) as fabrication method and the micro-tomographic reconstruction of an open-cell polymeric sponge as input virtual model to the printing system, in the attempt to replicate the trabecular architecture of cancellous bone. Additively-manufactured scaffolds were investigated from morphological (scanning electron microscopy), microstructural (X-ray diffraction), mechanical (compressive tests) and bioactive viewpoints (immersion studies in simulated body fluid (SBF)). Well-densified foam-like glass scaffolds were obtained after sintering, provided with suitable mechanical properties (compressive strength 21.9 ± 6.2 MPa, elastic modulus 4.8 ± 0.1 GPa, Weibull modulus 3.9) for bone-contact applications. The formation of a hydroxyapatite layer on scaffold struts after soaking in SBF also demonstrated the in vitro bioactivity of the printed structures.

Porosity is a key feature in dictating the overall performance of biomedical scaffolds, with special relevance to mechanical properties. Usually, compressive strength and elastic modulus are the main parameters used to determine the potential mechanical suitability of porous scaffolds for bone repair. However, their assessment may not be so easy from an experimental viewpoint and, especially if the porosity is high, so reliable for brittle bioceramic foams. Hence, assessing the relationship between porosity and mechanical properties based only on the constitutive parameters of the solid material is a challenging and important task to predict the scaffold performance for optimization during design. In this work, a set of equations was used to predict the compressive strength and elastic modulus of bone-like hydroxyapatite scaffolds produced by digital light processing-based vat photopolymerization (total porosity about 80 vol.%). The compressive strength was found to depend on total porosity, following a power-law approximation. The relationship between porosity and elastic modulus was well fitted by second-order power law, with relative density and computational models obtained by numerical simulations.

Abstract In bone tissue engineering research, bioreactors designed for replicating the main features of the complex native environment represent powerful investigation tools. Moreover, when equipped with automation, their use allows reducing user intervention and dependence, increasing reproducibility and the overall quality of the culture process. In this study, an automated uni-/bi-directional perfusion bioreactor combinable with pulsed electromagnetic field (PEMF) stimulation for culturing 3D bone tissue models is proposed. A user-friendly control unit automates the perfusion, minimizing the user dependency. Computational fluid dynamics simulations supported the culture chamber design and allowed the estimation of the shear stress values within the construct. Electromagnetic field simulations demonstrated that, in case of combination with a PEMF stimulator, the construct can be exposed to uniform magnetic fields. Preliminary biological tests on 3D bone tissue models showed that perfusion promotes the release of the early differentiation marker alkaline phosphatase. The histological analysis confirmed that perfusion favors cells to deposit more extracellular matrix (ECM) with respect to the static culture and revealed that bi-directional perfusion better promotes ECM deposition across the construct with respect to uni-directional perfusion. Lastly, the Real-time PCR results of 3D bone tissue models cultured under bi-directional perfusion without and with PEMF stimulation revealed that the only perfusion induced a ~ 40-fold up-regulation of the expression of the osteogenic gene collagen type I with respect to the static control, while a ~ 80-fold up-regulation was measured when perfusion was combined with PEMF stimulation, indicating a positive synergic pro-osteogenic effect of combined physical stimulations.

Cancer is one of the most life-threatening family of diseases that cause death worldwide. As a highly researched and successful therapeutic agent, methotrexate (MTX) treats many solid tumours, hematologic malignancies, and autoimmune illnesses. Despite many benefits, methotrexate induces drug resistance and limits plasma half-life due to its poor pharmacokinetics. The variable biological availability have prompted researchers to investigate innovative delivery strategies for enhancing its therapeutic qualities. To develop more suitable methotrexate formulations, nanoparticles (NPs) have recently gained a significant interest. A wide range of nanoparticles, including polymer-based nanoparticles, carbon-based nanoparticles, lipid-based nanoparticles, as well as inorganic nanoparticles, can be deliver cancer chemotherapeutics such as methotrexate. Loading methotrexate into NPs can provide a delivery system that has shown great promise to carcinoma therapy. In this review, we will describe the feasibility of NP-based strategies to deliver methotrexate in cancer therapy, outlining the current state of the art and the challenges/promises for the future.

Neoplastic cells have co-opted inflammatory receptors and signaling molecules that potentiate inflammation. Activated inflammatory pathways lead to neo-angiogenesis, lymph-angiogenesis, immunosuppression, tumor growth, proliferation and metastasis. This cancer-sustaining inflammation is a critical target to arrest cancer growth. Multiple drug resistance, high cost, low oral bioavailability and serious side effects have rendered conventional cytotoxic chemotherapeutics less impressive. The aim of this research was to achieve cancer debulking and proliferation prevention by limiting ‘cancer-sustaining’ tumor niche inflammation through non-conventional oral approach employing anti-inflammatory agents and avoiding conventional cytotoxic agents. Synergistic anti-inflammatory agents, i.e. celecoxib as selective COX-2 inhibitor and montelukast as cysteinyl leukotriene receptor antagonist, were selected. Silver nanoparticles (AgNPs) were used as nanocarriers because of their efficient synergistic anti-neoplastic effects and excellent oral drug delivery potential. Specifically, selected drugs were co-conjugated onto AgNPs. Synthesized nanoparticles were then surface-modified with poly(vinyl alcohol) to control particle size, avoid opsonization/preferred cellular uptake and improve dispersion. Surface plasmon resonance analysis, particle size analysis, DSC, TGA, XRD, FTIR and LIBS analysis confirmed the successful conjugation of drugs and efficient polymer coating with high loading efficiency. In-vitro, the nanoparticles manifested best and sustained release in moderately acidic (pH 4.5) milieu enabling passive tumor targeting potential. In-vivo, synthesized nanoparticles exhibited efficient dose-dependent anti-inflammatory activity reducing the dose up to 25-fold. The formulation also manifested hemo-compatibility, potent anti-denaturation activity and dose-dependent in-vitro and in-vivo anti-cancer potential against MCF-7 breast cancer and Hep-G2 liver cancer cell lines in both orthotopic and subcutaneous xenograft cancer models. The anti-inflammatory nanoparticles manifested tumor specific release potential exhibiting selective cytotoxicity at cancerous milieu with slightly acidic environment and activated inflammatory pathways. The formulation displayed impressive oral bioavailability, sustained release, negligible cytotoxicity against THLE-2 normal human hepatocytes, low toxicity (high LD50) and wide therapeutic window. Results suggest promise of developed nanomaterials as hemo-compatible, potent, cheaper, less-toxic oral anti-inflammatory and non-conventional anti-cancer agents.

Biocompatible ceramics, commonly known as “bioceramics”, are an extremely versatile class of materials with a wide range of applications in modern medicine. Given the inorganic nature and physico-mechanical properties of most bioceramics, which are relatively close to the mineral phase of bone, orthopedics and dentistry are the preferred areas of usage for such biomaterials. Another clinical field where bioceramics play an important role is oculo-orbital surgery, a highly cross- and interdisciplinary medical specialty addressing to the management of injured eye orbit, with particular focus on the repair of orbital bone fractures and/or the placement of orbital implants following removal of a diseased eye. In the latter case, orbital implants are not intended for bone repair but, being placed inside the ocular cavity, have to be biointegrated in soft ocular tissues. This article reviews the state of the art of currently-used bioceramics in orbital surgery, highlighting the current limitations and the promises for the future in this field.

Implantation of three-dimensional (3D) bioactive glass-derived porous scaffolds is an effective strategy for promoting bone repair and regeneration in large osseous defect sites. The present study intends to expand the potential of a SiO2–P2O5–CaO–MgO–Na2O–CaF2 glass composition, which has already proven to be successful in regenerating bone in both animals and human patients. Specifically, this research work reports the fabrication of macroporous glass–ceramic scaffolds by the foam replica method, using the abovementioned bioactive glass powders as a parent material. The sinter-crystallization of the glass powder was investigated by hot-stage microscopy, differential thermal analysis, and X-ray diffraction. Scanning electron microscopy was used to investigate the pore–strut architecture of the resultant glass–ceramic scaffolds in which diopside, fluorapatite, and wollastonite crystallized during thermal treatment. Immersion studies in simulated body fluids revealed that the scaffolds have bioactive behavior in vitro; the mechanical properties were also potentially suitable to suggest use in load-bearing bone applications.

Abstract In this study, paclitaxel (PTX)-loaded pH-responsive niosomes modified with ergosterol were developed. This new formulation was characterized in terms of size, morphology, encapsulation efficiency (EE), and in vitro release at pH 5.2 and 7.4. The in vitro efficacy of free PTX and niosome/PTX was assessed using MCF7, Hela, and HUVEC cell lines. In order to evaluate the in vivo efficacy of niosomal PTX in rats as compared to free PTX, the animals were intraperitoneally administered with 2.5 mg/kg and 5 mg/kg niosomal PTX for two weeks. Results showed that the pH-responsive niosomes had a nanometric size, spherical morphology, 77% EE, and pH-responsive release in pH 5.2 and 7.4. Compared with free PTX, we found markedly lower IC50s when cancer cells were treated for 48 h with niosomal PTX, which also showed high efficacy against human cancers derived from cervix and breast tumors. Moreover, niosomal PTX induced evident morphological changes in these cell lines. In vivo administration of free PTX at the dose of 2.5 mg/kg significantly increased serum biochemical parameters and liver lipid peroxidation in rats compared to the control rats. The situation was different when niosomal PTX was administered to the rats: the 5 mg/kg dosage of niosomal PTX significantly increased serum biochemical parameters, but the group treated with the 2.5 mg/kg dose of niosomal PTX showed fewer toxic effects than the group treated with free PTX at the same dosage. Overall, our results provide proof of concept for encapsulating PTX in niosomal formulation to enhance its therapeutic efficacy.

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.

Direct-Ink-Writing (or robocasting) is a subset of extrusion-based additive manufacturing techniques that has grown significantly in recent years to design simple to complex ceramic structures. Robocasting, relies on the use of high-concentration powder pastes, also known as inks. A successful optimization of ink rheology and formulation constitutes the major key factor to ensure printability for the fabrication of self-supporting ceramic structures with a very precise dimensional resolution. However, to date achieving a real balance between a comprehensive optimization of ink rheology and the determination of a relevant protocol to predict the printing parameters for a given ink is still relatively scarce and has been not yet standardized in the literature.The current review reports, in its first part, a detailed survey of recent studies on how ink constituents and composition affect the direct-ink-writing of ceramic parts, taking into account innovative ceramic-based-inks formulations and processing techniques. Precisely, the review elaborates the major factors influencing on ink rheology and printability, specifically binder type, particle physical features (size, morphology and density) and ceramic feedstock content.In the second part, this review suggests a standardized guideline to effectively adapt a suitable setting of the printing parameters, such as printing speed and pressure, printing substrate, strut spacing, layer height, nozzle diameter in function of ink intrinsic rheology.

The utilization of bioactive glasses (BGs) in cancer therapy has recently become quite promising; herein, a series of Fe-doped mesoporous 45S5-based BGs (MBGs) were synthesized via the sol-gel method in the presence of Pluronic P123 as a soft template. The physico-chemical and biological properties of the prepared glasses were well-characterized through structural assessments, thermal analyses, and electron microscopic studies. Electrochemical analyses, including cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), were also performed to investigate the actual potential of the Fe2O3-containing MBGs in modulating the Fenton's reaction. The XRD results confirmed the glassy state of the Fe-doped samples before immersion in simulated body fluid (SBF). The prepared Fe-doped MBGs exhibited a particle size in the range of 11–86 nm, surface charge of 27–30 mV, SBET of 95–306 m2/g, and Ms of 0.08 to 0.2 emu/g. The incorporation of Fe2O3 led to a negligible decrease in the bioactivity of the glasses. The CV analysis indicated that the Fe-doped MBGs could generate H2O2 in a cathodic potential higher than -0.2 V (vs. Ag/AgCl) in the O2-saturated Na2SO4 solution. Additionally, the data of the EIS test revealed that the Fe2O3-doped MBGs could increase the standard rate constant of Electro-Fenton's (EF) reaction up to 38.44 times as compared with the Fe-free glasses. In conclusion, Fe-doped 45S5-derived glasses may be useful in cancer therapy strategies due to their capability of activating Fenton's reaction and subsequent production of reactive oxygen species (ROS) such as •OH free radicals.

Promoting bone healing is a key challenge in our society that can be tackled by developing new implantable biomaterials provided with regenerative properties. In this work, the coating of three-dimensional porous glass-derived scaffolds with hyaluronic acid (HA)-fatty acids was investigated for the first time. The starting scaffolds, based on bioactive silicate glass, were produced by foam replication followed by sintering; then, HA-palmitate and HA-oleate conjugate coatings were deposited on the scaffold struts through a dipping procedure. FT-IR analysis confirmed the successful deposition of the coatings on the surface and struts of the scaffolds, the foam-like architecture of which was maintained as assessed by SEM investigations. The in vitro bioactivity of the HA–fatty-acid-coated scaffolds was studied by immersion tests in simulated body fluid and the subsequent evaluation of hydroxyapatite formation. The deposition of the polymeric coating did not inhibit the apatite-forming ability of scaffolds, as revealed by the formation of nanostructured hydroxyapatite agglomerates 48 h from immersion. These promising results motivate further investigation of these novel bioactive systems, which are expected to combine the bone-bonding properties of the glass with the wound-healing promotion carried out by the polymeric conjugates.

Electrospun nanofibrous constructs based on nanoparticles and biopolymers have recently been used in tissue engineering because of their similarity to the extracellular matrix in nature. In this study, electrospun chitosan-carbon quantum dot-titanium dioxide-graphene oxide (CS-CQD-TiO2-GO) nanofibrous mats were synthesized for use as wound dressings by the electrospinning method. To increase the biodegradation rate and water resistance, the fabricated nanofibrous mats were cross-linked. SEM images showed a uniform and coherent structure of CS-CQD-TiO2-GO nanocomposites and CS-CQD-TiO2-GO electrospun nanofibers mats. FTIR analysis, XRD pattern, SEM mapping, and EDS spectrum demonstrate the accuracy of the synthesis as well as the elemental and chemical structure of the nanofibrous mat. The water contact angle indicated that the nanofibrous mat had a hydrophilic property, which is essential for controlling wound exudates. The tensile strength and elongation tests showed that the nanofibrous mat has suitable mechanical properties for wound dressing, including significant flexibility and strength. Interestingly, antimicrobial testing illustrated that the fabricated nanofibrous mat had antibacterial activity against Gram-negative and Gram-positive bacteria. Appropriate cell viability and cytocompatibility of treated mouse fibroblast NIH3T3 cells with the nanofibrous mat were determined using an MTT assay. The animal study results confirmed the proper potential of the nanofibrous mat in wound dressing applications.

Elevated levels of oxidative stress are usually observed following injuries, leading to impaired tissue repair due to oxidation-related chronic inflammation. Several attempts have been made to manage this unfavorable situation, and the use of biomaterials with antioxidant activity is showing great promise in tissue engineering and regenerative medicine approaches. Bioactive glasses (BGs) are a versatile group of inorganic substances that exhibit an outstanding regenerative capacity for both hard and soft damaged tissues. The chemical composition of BGs provides a great opportunity for imparting specific biological activities to them. On this point, BGs may easily become antioxidant substances through simple physicochemical modifications. For example, particular antioxidant elements (mostly cerium (Ce)) can be added to the basic composition of the glasses. On the other hand, grafting natural antioxidant substances (e.g., polyphenols) on the BG surface is feasible for making antioxidant substitutes with promising results in vitro. Mesoporous BGs (MBGs) were demonstrated to have unique merits compared with melt-derived BGs since they make it possible to load antioxidants and deliver them to the desired locations. However, there are actually limited in vivo experimental studies on the capability of modified BGs for scavenging free radicals (e.g., reactive oxygen species (ROS)). Therefore, more research is required to determine the actual potential of BGs in decreasing oxidative stress and subsequently improving tissue repair and regeneration. The present work aims to highlight the potential of different types of BGs in modulating oxidative stress and subsequently improving tissue healing.

Site-specific drug delivery and carrying repairing agents for wound healing purposes can be achieved using the intertwined three-dimensional structure of nanofibers. This study aimed to optimize and fabricate poly (vinyl alcohol) (PVA)-graphene oxide (GO)-silver (Ag) nanofibers containing curcumin (CUR) using the electrospinning method for potential wound healing applications. Fourier Transform Infrared (FTIR) spectrophotometry, X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS), and zeta potential were used to characterize the nanostructures. The mechanical properties of the nanostructures were subsequently examined by tensile strength and elongation test. As shown by MIC analysis of E. coli and S. aureus bacteria, the fabricated nanofibers had superior inhibitory effects on the bacteria growth. Ag nanoparticles incorporation into the nanofibers resulted in increased loading and encapsulation efficiencies from 21% to 56% and from 61% to 86%, respectively. CUR release from PVA/GO-Ag-CUR nanofiber at pH 7.4 was prevented, while the acidic microenvironment (pH 5.4) increased the release of CUR from PVA/GO-Ag-CUR nanofiber, corroborating the pH-sensitivity of the nanofibers. Using the in vitro wound healing test on NIH 3T3 fibroblast cells, we observed accelerated growth and proliferation of cells cultured on PVA/GO-Ag-CUR nanofibers.

Bacillus bacteria are a group of plant growth stimulants that increase plant growth and resistance to plant pathogens by producing various metabolites. With their large surface area and small size, nanoparticles can be used in controlled-release formulations and increase the efficiency of the desired product. Encapsulation of biological agents in combination with nanoparticles can be an essential step in increasing the performance of these agents in adverse environmental conditions. In this study, which is the result of a collaboration between scientists from Italy and Iran, Bacillus velezensis was encapsulated in alginate combined with whey protein and zedo, mastic, and tragacanth gums in the presence of silica and titania nanoparticles to obtain two-layer and multilayer assemblies acting as novel, smart micro-encapsulation systems. The results of laboratory studies showed that the B. velezensis could produce protease, lipase, siderophore, auxin, and a dissolution of mineral phosphate. Scanning electron microscopy images (SEM) showed that the studied microcapsules were almost spherical. Moisture affinity, swelling, and efficiency of each microcapsule were examined. The results showed that the highest encapsulation efficiency (94.3%) was related to the multilayer formulation of alginate-whey protein-zedo. XRD and FTIR spectroscopy showed that the alginate, whey protein, and zedo were mixed properly and no incompatible composition occurred in the reaction. This study aimed to provide a suitable formulation of biofertilizers based on biodegradable compounds as an alternative to chemical fertilizers, which is low cost and very effective without harming humans and the environment.

Beyond their well-known applications in bone tissue engineering, hydroxyapatite nanoparticles (HAp NPs) have also been showing great promise for improved cancer therapy. The chemical structure of HAp NPs offers excellent possibilities for loading and delivering a broad range of anticancer drugs in a sustained, prolonged, and targeted manner and thus eliciting lower complications than conventional chemotherapeutic strategies. The incorporation of specific therapeutic elements into the basic composition of HAp NPs is another approach, alone or synergistically with drug release, to provide advanced anticancer effects such as the capability to inhibit the growth and metastasis of cancer cells through activating specific cell signaling pathways. HAp NPs can be easily converted to smart anticancer agents by applying different surface modification treatments to facilitate the targeting and killing of cancer cells without significant adverse effects on normal healthy cells. The applications in cancer diagnosis for magnetic and nuclear in vivo imaging are also promising as the detection of solid tumor cells is now achievable by utilizing superparamagnetic HAp NPs. The ongoing research emphasizes the use of HAp NPs in fabricating three-dimensional scaffolds for the treatment of cancerous tissues or organs, promoting the regeneration of healthy tissue after cancer detection and removal. This review provides a summary of HAp NP applications in cancer theranostics, highlighting the current limitations and the challenges ahead for this field to open new avenues for research.

Bioactive glasses are often designed as porous implantable templates in which newly-formed bone can grow in three dimensions (3D). This research work aims to investigate the bone regenerative capability of silicate bioactive glass scaffolds produced by robocasting in comparison with powder and granule-like materials (oxide system: 47.5SiO2-10Na2O-10K2O-10MgO-20CaO-2.5P2O5, mol.%). Morphological and compositional analyses performed by scanning electron microscopy (SEM), combined with energy dispersive spectroscopy (EDS) after the bioactivity studies in a simulated body fluid (SBF) confirmed the apatite-forming ability of the scaffolds, which is key to allowing bone-bonding in vivo. The scaffolds exhibited a clear osteogenic effect upon implantation in rabbit femur and underwent gradual resorption followed by ossification. Full resorption in favor of new bone growth was achieved within 6 months. Osseous defect healing was accompanied by the formation of mature bone with abundant osteocytes and bone marrow cells. These in vivo results support the scaffold’s suitability for application in bone tissue engineering and show promise for potential translation to clinical assessment.

A copper oxide/cerium oxide nanocomposite (CuO/CeO2, NC) was synthesized via a novel method using a metal–organic framework as a precursor. This nanomaterial was characterized by Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), dynamic light scattering size analysis (DLS), and zeta potential. The PXRD showed the successful synthesis of the CuO/CeO2 NC, in which the 2theta values of 35.55° (d = 2.52 Å, 100%) and 38.73° (d = 2.32 Å, 96%) revealed the existence of copper (II) oxide. FTIR analysis showed the CeO2, hydroxyl groups, absorbed water, and some residual peaks. The solid phase analysis by FESEM and TEM images showed mean particle sizes of 49.18 ± 24.50 nm and 30.58 ± 26.40 nm, respectively, which were comparable with crystallite size (38.4 nm) obtained from PXRD, but it appears the CuO/CeO2 NC was not evenly distributed and in some areas, showed it was highly agglomerated. The hydrodynamic size (750.5 nm) also showed the agglomeration of the CuO/CeO2 NCs in the solution, which had a negatively charged surface. The CuO/CeO2 NCs showed anti-proliferative activity against human breast cancer cell line (MCF-7) in a dose- and time-dependence way, while affecting normal cells less significantly.

The combination of biocompatible polymers and ceramics shows great promise in the development of composites with suitable mechanical properties for dental applications. In an attempt to further expand this research line, Al2O3 commercial powders (Vitro-ceram, Alglass, In-ceram) were sintered at 1400 °C for 2 h and infiltrated with poly(methyl methacrylate) for potential use in dental prostheses. The infiltration was performed using a homemade apparatus under a pressure of 7 bar for 6 and 12 h. The microstructure (studied using a scanning electron microscope), Archimedes density, 3-point bending flexural strength and Vickers hardness of the prepared composites were assessed and quantitatively compared. In general, microstructural analyses showed ceramic- and polymer-based interpenetrating network in all materials. The preforms infiltrated for 12 h showed superior properties; among them, the Vitro-ceram-based composite also demonstrated a near-zero open porosity and optimum mechanical characteristics. Specifically, its density, strength and hardness were 2.6 ± 0.07 g/cm3, 119.3 ± 5.0 MPa and 1055.1 ± 111.0 HV, respectively, passing the acceptance criteria of ISO 6872 and making it suitable for consideration as a metal-free structure for dental crowns and fixed partial prostheses until three anterior units.

Hydroxyapatite (HAp) has been considered for decades an ideal biomaterial for bone repair due to its compositional and crystallographic similarity to bioapatites in hard tissues. However, fabrication of porous HAp acting as a template (scaffold) for supporting bone regeneration and growth has been a challenge to biomaterials scientists. The introduction of additive manufacturing technologies, which provide the advantages of a relatively fast, precise, controllable, and potentially scalable fabrication process, has opened new horizons in the field of bioceramic scaffolds. This review focuses on three-dimensional-printed HAp scaffolds and related composite systems, where the calcium phosphate phase is combined with other ceramics or polymers improving the mechanical properties and/or imparting special extra-functionalities. The main applications of three-dimensional-printed HAp scaffolds in bone tissue engineering are presented and discussed; furthermore, this review also emphasizes the most recent achievements toward the development and testing of multifunctional HAp-based systems combining multiple properties for advanced therapy (e.g., bone regeneration, antibacterial effect, angiogenesis, and cancer treatment).

Improving and accelerating bone repair still are partially unmet needs in bone regenerative therapies. In this regard, strontium (Sr)-containing bioactive glasses (BGs) are highly-promising materials to tackle this challenge. The positive impacts of Sr on the osteogenesis makes it routinely used in the form of strontium ranelate (SR) in the clinical setting, especially for patients suffering from osteoporosis. Therefore, a large number of silicate-, borate-, and phosphate-based BGs doped with Sr and produced in different shapes have been developed and characterized, in order to be used in the most advanced therapeutic strategies designed for the management of bone defects and injuries. Although the influence of Sr incorporation in the glass is debated regarding the obtained physicochemical and mechanical properties, the biological improvements have been found to be substantial both in vitro and in vivo. In the present study, we provide a comprehensive overview of Sr-containing glasses along with the current state of their clinical use. For this purpose, different types of Sr-doped BG systems are described, including composites, coatings and porous scaffolds, and their applications are discussed in the light of existing experimental data along with the significant challenges ahead.

The management of burn injuries is considered an unmet clinical need and, to date, no fully satisfactory solution exists to this problem. This mini-review aims to explore the potential of bioactive glasses (BGs) for burn care due to the therapeutic effects of their ionic dissolution products. BGs have been studied for more than 40 years and boast a long successful history in the substitution of damaged tissues, especially bone. Considering their exceptional versatility and attractive characteristics, these synthetic materials have also recently been proposed in the treatment of soft tissue-related disorders such as skin wounds. Specifically, improving fibroblast proliferation, inducing angiogenesis, and eliciting antibacterial activity (with the additional advantage of avoiding administration of antibiotics) are all considered as key added values carried by BGs in the treatment of burn injuries. However, some issues deserve careful consideration while proceeding with the research, including the selection of suitable BG compositions, appropriate forms of application (e.g., BG fibers, ointments or composite patches), as well as the procedures for reliable in vivo testing.

The polyol method has been used to synthesize CoNiFe and CoNiZn alloy nanoparticles (NPs). The magnetic characteristics of the products have been measured by vibration sample magnetometry (VSM) analysis. At the same time, the microstructure and morphology were inspected by X-ray diffraction (XRD) and scanning electron microscopy (SEM), respectively. Magnetic measurement of samples by the VSM indicated that samples have soft ferromagnetic behavior. Spherical-shaped grains for samples were confirmed by the SEM. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and lactate dehydrogenase (LDH) assays were used to determine the cytotoxic effects of the synthesized NPs. Cytotoxic evaluations showed that treatment with 25 to 400 µg/mL of CoNiZn and CoNiFe NPs exerted a significant time- and concentration-dependent toxicity in MCF7 and HUVEC cells and markedly enhanced the LDH leakage after 48 h of exposure (p < 0.05 compared with untreated cells). Furthermore, NPs with concentrations higher than 12.5 µg/mL induced evident morphological changes in the studied cell lines. Treatment with 12.5 µg/mL of CoNiZn and CoNiFe NPs was safe and did not affect normal human cell survival. The results of in vitro cytotoxicity assessments show promise in supporting the suitability of the synthesized NPs to build high-performance theranostic nanoplatforms for simultaneous cancer imaging and therapy without affecting normal human cells.

In this study, the biosynthesis of zinc oxide nanoparticles using Aspergillus niger (A/ZnO-NPs) is described. These particles have been characterized by UV–Vis spectrum analysis, X-ray powder diffraction, field emission scanning electron microscopy, and transmission electron microscopy. To use this biosynthesized nanoparticle as an antiproliferative and antimicrobial agent, the IC50 value against the breast cancer cell line and inhibition zone against Escherichia coli were used to optimize the effect of two processing factors including dose of filtrate fungi cell and temperature. The biosynthesized A/ZnO-NPs had an absorbance band at 320 nm and spherical shapes. The mean particles size was 35 nm. RSM (response surface methodology) was utilized to investigate the outcome responses. The Model F-value of 12.21 and 7.29 implies that the model was significant for both responses. The contour plot against inhibition zone for temperature and dose showed that if the dose increases from 3.8 to 17.2 µg/mL, the inhibition zone increases up to 35 mm. As an alternative to chemical and/or physical methods, biosynthesizing zinc oxide NPs through fungi extracts can serve as a more facile and eco-friendly strategy. Additionally, for optimization of the processes, the outcome responses in the biomedical available test can be used in the synthesis of ZnO-NPs that are utilized for large-scale production in various medical applications.

The use of naturally occurring materials in biomedicine has been increasingly attracting the researchers’ interest and, in this regard, gum tragacanth (GT) is recently showing great promise as a therapeutic substance in tissue engineering and regenerative medicine. As a polysaccharide, GT can be easily extracted from the stems and branches of various species of Astragalus. This anionic polymer is known to be a biodegradable, non-allergenic, non-toxic, and non-carcinogenic material. The stability against microbial, heat and acid degradation has made GT an attractive material not only in industrial settings (e.g., food packaging) but also in biomedical approaches (e.g., drug delivery). Over time, GT has been shown to be a useful reagent in the formation and stabilization of metal nanoparticles in the context of green chemistry. With the advent of tissue engineering, GT has also been utilized for the fabrication of three-dimensional (3D) scaffolds applied for both hard and soft tissue healing strategies. However, more research is needed for defining GT applicability in the future of biomedical engineering. On this object, the present review aims to provide a state-of-the-art overview of GT in biomedicine and tries to open new horizons in the field based on its inherent characteristics.

Curcumin is known to exhibit antioxidant and tissue-healing properties and has recently attracted the attention of the biomedical community for potential use in advanced therapies. This work reports the formulation and characterization of oil-in-water F127 microemulsions to enhance the bioavailability of curcumin Microemulsions showed a high encapsulation efficiency and prolonged release. To investigate the interactions of curcumin with one unit of the polymeric chain of surfactant F127, ethyl butyrate, and sodium octanoate, as well as the interaction between ethyl butyrate and one unit of the F127 polymer chain, the Density Functional Theory (DFT) calculations at the M06-2X level of theory, were performed in water solution. The MTT assay was used to assess the cytotoxicity of free and encapsulated curcumin on non-malignant and malignant cell lines. Combination effects were calculated according to Chou-Talalay’s principles. Results of in vitro studies indicated that MCF7 and HepG2 cells were more sensitive to curcumin microemulsions. Moreover, a synergistic relationship was observed between curcumin microemulsions and cisplatin in all affected fractions of MCF7 and HepG2 cells (CI < 0.9). For in vivo investigation, thioacetamide-intoxicated rats received thioacetamide (100 mg/kg Sc) followed by curcumin microemulsions (30 mg/kg Ip). Thioacetamide-intoxicated rats showed elevated serum liver enzymes, blood urea nitrogen (BUN), and creatinine levels, and a significant reduction in liver superoxide dismutase (SOD) and catalase (CAT) activities (p < 0.05). Curcumin microemulsions reduced liver enzymes and serum creatinine and increased the activity of antioxidant enzymes in thioacetamide-treated rats in comparison to the untreated thioacetamide-intoxicated group. Histopathological investigations confirmed the biochemical findings. Overall, the current results showed the desirable hepatoprotective, nephroprotective, and anti-cancer effects of curcumin microemulsions.

The development of effective strategies for local administration of chemotherapeutic drugs, thus minimizing the adverse side effects to patients, is one of the key challenges in biomedicine and cancer research. This work reports the formulation and characterization of PluronicF127 microemulsions to enhance the bioavailability of Cisplatin (Cis). The size of Cis microemulsion was about 12.0 nm, as assessed by dynamic light scattering analysis. In vitro cytotoxic activity of free Cis and F127/Cis microemulsions were studied on malignant (C152 and MCF7) and normal (HUVEC) cells via tetrazolium (MTT) colorimetric assay. Cell morphology was also monitored. In vitro assessments revealed thatF127/Cis microemulsions induced cytotoxicity/morphological changes to a lesser extent than free Cis. Regarding in vivo experiments, F127/Cis microemulsions were injected intraperitoneally at 7 and 14 mg/kg doses into adult male Wistar rats to assess histologic and biochemical changes. In this case, the bulk Cis group caused severe histopathological changes and significant increases in serum liver enzymes and serum kidney function markers. The group treated with the 14 mg/kg dose of F127/Cis microemulsions also showed severe fatty changes and significant increases in serum liver enzymes, blood urea nitrogen, and creatinine levels. The group treated with the low dose of nano-Cis showed a significant increase in serum liver enzymes levels accompanied by mild fatty changes of the liver. Theoretical surveys were performed to get an understanding of the interplay between F127 and Cis. Results reveal that hydrogen bonding (HB) interactions with F127have an influence on the molecular properties of Cis and may playa role in the lower toxicity of F127/Cis in comparison to free Cis.

Developing new therapeutic drugs to prevent ischemia/reperfusion (I/R)-induced renal injuries is highly pursued. Liposomal encapsulation of spironolactone (SP) as a mineralocorticoid antagonist increases dissolution rate, bioavailability and prevents the drug from degradation. In this context, this work develops a new formulation of oil-in-water type microemulsions to enhance the bioavailability of SP. The size of the SP-loaded microemulsion was about 6.0 nm by dynamic light scattering analysis. Briefly, we investigated the effects of nano-encapsulated SP (NESP) on renal oxidative stress, biochemical markers and histopathological changes in a rat model of renal I/R injury. Forty eight male Wistar rats were divided into six groups. Two groups served as control and injury model (I/R). Two groups received “conventional” SP administration (20 mg/kg) and NESP (20 mg/kg), respectively, for two days. The remaining two groups received SP (20 mg/kg) and NESP (20 mg/kg) two days before induction of I/R. At the end of the experiments, serum and kidneys of rats underwent biochemical, molecular and histological examinations. Our results showed that I/R induces renal oxidative stress, abnormal histological features and altered levels of renal biomarkers. Administration of SP in healthy animals did not cause any significant changes in the measured biochemical and histological parameters compared to the control group. However, SP administration in the I/R group caused some corrections in renal injury, although it could not completely restore I/R-induced renal oxidative stress and kidney damage. On the contrary, NESP administration restored kidney oxidative injury via decreasing renal lipid peroxidation and enhancing glutathione, superoxide dismutase and catalase in kidneys of the I/R group. The deviated serum levels of urea, creatinine, total proteins and uric acid were also normalized by NESP administration. Furthermore, NESP protected against renal abnormal histology features induced by I/R. Therefore, NESP has beneficial effects in preventing kidney damage and renal oxidative stress in a rat model of I/R, which deserves further evaluations in the 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.

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–MgO–Na2O–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 600–850 °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.

Several biocompatible materials have been applied for managing soft tissue lesions; cerium oxide nanoparticles (CNPs, or nanoceria) are among the most promising candidates due to their outstanding properties, including antioxidant, anti-inflammatory, antibacterial, and angiogenic activities. Much attention should be paid to the physical properties of nanoceria, since most of its biological characteristics are directly determined by some of these relevant parameters, including the particle size and shape. Nanoceria, either in bare or functionalized forms, showed the excellent capability of accelerating the healing process of both acute and chronic wounds. The skin, heart, nervous system, and ophthalmic tissues are the main targets of nanoceria-based therapies, and the other soft tissues may also be evaluated in upcoming experimental studies. For the repair and regeneration of soft tissue damage and defects, nanoceria-incorporated film, hydrogel, and nanofibrous scaffolds have been proven to be highly suitable replacements with satisfactory outcomes. Still, some concerns have remained regarding the long-term effects of nanoceria administration for human tissues and organs, such as its clearance from the vital organs. Moreover, looking at the future, it seems necessary to design and develop three-dimensional (3D) printed scaffolds containing nanoceria for possible use in the concepts of personalized medicine.

Some special implantable materials are defined as “bioactive” if they can bond to living bone, forming a tight and chemically-stable interface. This property, which is inherent to some glass compositions, or can be induced by applying appropriate surface treatments on otherwise bio-inert metals, can be evaluated in vitro by immersion studies in simulated body fluid (SBF), mimicking the composition of human plasma. As a result, apatite coating may form on the material surface, and the presence of this bone-like “biomimetic skin” is considered predictive of bone-bonding ability in vivo. This review article summarizes the story and evolution of in vitro bioactivity testing methods using SBF, highlighting the influence of testing parameters (e.g., formulation and circulation of the solution) and material-related parameters (e.g., composition, geometry, texture). Suggestions for future methodological refinements are also provided at the end of the paper.

Angiogenesis (or the development of new blood vessels) is a key event in tissue engineering and regenerative medicine; thus, a number of biomaterials have been developed and combined with stem cells and/or bioactive molecules to produce three-dimensional (3D) pro-angiogenic constructs. Among the various biomaterials, electrospun nanofibrous scaffolds offer great opportunities for pro-angiogenic approaches in tissue repair and regeneration. Nanofibers made of natural and synthetic polymers are often used to incorporate bioactive components (e.g., bioactive glasses (BGs)) and load biomolecules (e.g., vascular endothelial growth factor (VEGF)) that exert pro-angiogenic activity. Furthermore, seeding of specific types of stem cells (e.g., endothelial progenitor cells) onto nanofibrous scaffolds is considered as a valuable alternative for inducing angiogenesis. The effectiveness of these strategies has been extensively examined both in vitro and in vivo and the outcomes have shown promise in the reconstruction of hard and soft tissues (mainly bone and skin, respectively). However, the translational of electrospun scaffolds with pro-angiogenic molecules or cells is only at its beginning, requiring more research to prove their usefulness in the repair and regeneration of other highly-vascularized vital tissues and organs. This review will cover the latest progress in designing and developing pro-angiogenic electrospun nanofibers and evaluate their usefulness in a tissue engineering and regenerative medicine setting.

Therapeutic advancements in the treatment of various ocular diseases is often linked to the development of efficient drug delivery systems (DDSs), which would allow a sustained release while maintaining therapeutic drug levels in the target tissues. In this way, ocular tissue/cell response can be properly modulated and designed in order to produce a therapeutic effect. An ideal ocular DDS should encapsulate and release the appropriate drug concentration to the target tissue (therapeutic but non-toxic level) while preserving drug functionality. Furthermore, a constant release is usually preferred, keeping the initial burst to a minimum. Different materials are used, modified, and combined in order to achieve a sustained drug release in both the anterior and posterior segments of the eye. After giving a picture of the different strategies adopted for ocular drug release, this review article provides an overview of the biomaterials that are used as drug carriers in the eye, including micro- and nanospheres, liposomes, hydrogels, and multi-material implants; the advantages and limitations of these DDSs are discussed in reference to the major ocular applications.

Bioactive glasses (BGs) have been identified as highly versatile materials in tissue engineering applications; apart from being used for bone repair for many years, they have recently shown promise for the regeneration of peripheral nerves as well. They can be formulated in different shapes and forms (micro-/nanoparticles, micro-/nanofibers, and tubes), thus potentially meeting the diverse requirements for neuroregeneration. Mechanical and biological improvements in three-dimensional (3D) polymeric scaffolds could be easily provided by adding BGs to their composition. Various types of silicate, borate, and phosphate BGs have been examined for use in neuroregeneration. In general, BGs show good compatibility with the nervous system compartments both in vitro and in vivo. Functionalization and surface modification plus doping with therapeutic ions make BGs even more effective in peripheral nerve regeneration. Moreover, the combination of BGs with conductive polymers is suggested to improve neural cell functions at injured sites. Taking advantage of BGs combined with novel technologies in tissue engineering, like 3D printing, can open new horizons in reconstructive approaches for the nervous system. Although there are great potential opportunities in BG-based therapies for peripheral nerve regeneration, more research should still be performed to carefully assess the pros and cons of BGs in neuroregeneration strategies.

The design and development of biomaterials with multifunctional properties is highly attractive in the context of bone tissue engineering due to the potential of providing multiple therapies and, thus, better treatment of diseases. In order to tackle this challenge, copper-doped silicate mesoporous bioactive glasses (MBGs) were synthesized via a sol-gel route coupled with an evaporation-induced self-assembly process by using a non-ionic block co-polymer as a structure directing agent. The structure and textural properties of calcined materials were investigated by X-ray powder diffraction, scanning-transmission electron microscopy and nitrogen adsorption-desorption measurements. In vitro bioactivity was assessed by immersion tests in simulated body fluid (SBF). Preliminary antibacterial tests using Staphylococcus aureus were also carried out. Copper-doped glasses revealed an ordered arrangement of mesopores (diameter around 5 nm) and exhibited apatite-forming ability in SBF along with promising antibacterial properties. These results suggest the potential suitability of copper-doped MBG powder for use as a multifunctional biomaterial to promote bone regeneration (bioactivity) and prevent/combat microbial infection at the implantation site, thereby promoting tissue healing.

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 “sustainable” 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.

The use of proper cells for bone tissue engineering remains a major challenge worldwide. Cells play a pivotal role in the repair and regeneration of the bone tissue in vitro and in vivo. Currently, a large number of differentiated (somatic) and undifferentiated (stem) cells have been used for bone reconstruction alone or in combination with different biomaterials and constructs (e.g., scaffolds). Although the results of the cell transplantation without any supporting or adjuvant material have been very effective with regard to bone healing. Recent advances in bone scaffolding are now becoming new players affecting the osteogenic potential of cells. In the present study, we have critically reviewed all the currently used cell sources for bone reconstruction and discussed the new horizons that are opening up in the context of cell-based bone tissue engineering strategies.