Search

Cancer, a significant threat to human lives, has been the target of research for several decades. Although conventional therapies have drawbacks, such as side effects, low efficacy, and weak targeting, they have been applied extensively due to a lack of effective alternatives. The emergence of nanotechnology in medicine has opened up new possibilities and offered promising solutions for cancer therapy. In recent years, 2D nanomaterials have attracted enormous attention in nanomedicine due to their large surface-to-volume ratio, photo-responsivity, excellent electrical conductivity, etc. Among them, black phosphorus (BP) is a 2D nanomaterial consisting of multiple layers weakly bonded together through van der Waals forces. Its distinct structure makes BP suitable for biomedical applications, such as drug/gene carriers, PTT/PDT, and imaging agents. BP has demonstrated remarkable potential since its introduction in cancer therapy in 2015, particularly due to its selective anticancer activity even without the aid of near-infrared (NIR) or anticancer drugs. The present review makes efforts to cover and discuss studies published on the anticancer activity of BP. Based on the type of cancer, the subcategories are organized to shed light on the potential of BP nanosheets and BP quantum dots (BPQDs) against breast, brain, skin, prostate, and bone cancers, and a section is devoted to other cancer types. Since extensive attention has been paid to breast cancer cells and in vivo models, various subsections, including mono-, dual, and triple therapeutic approaches are established for this cancer type. Furthermore, the review outlines various synthesis approaches employed to produce BP nanomaterials, providing insights into key synthesis parameters. This review provides an up-to-date platform for the potential reader to understand what has been done about BP cancer therapy based on each disease, and the conclusions and outlook cover the directions in which this approach is going to proceed in the future.

Face masks represent a valuable tool to prevent the spreading of airborne viruses; however, they show poor comfort and scarce antiviral efficacy. Zein-based coatings are herein exploited to enhance antiviral performance. Zein functionalization is done through acidifying agents (lactic acid, LA). Coatings are characterized in terms of morphological, mechanical, breathability, and cytotoxicity analyses. The antiviral efficacy is tested in vitro against four viruses (Human Coronavirus OC43, Herpes Simplex Virus type 1, Human Adenovirus type 5, and MPox Virus) according to a biological assay on cell cultures. Zein/Zein LA antiviral activity seems to be linked to its positive surface charge that enables to form electrostatic interactions with negatively charged-viruses, resulting in the highest activity (reduction >2 Log) on Human Coronavirus OC43 and Herpes Simplex Virus type 1, with efficacy comparable or higher than that of copper/copper oxide-based- coatings. No significant activity is observed against Human Adenovirus type 5 and MPox Virus, due to their high resistance to inactivating treatments. Zein-based systems are not cytotoxic and their water vapor permeability is reduced of 26 % compared to that of not-coated systems. These promising results offer interesting insights into design of antiviral and sustainable coatings for personal protective equipment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Currently, an important ecological problem is environmental pollution and its negative impact on living organisms, the consequences of which are deterioration in general health and the manifestation of various diseases, poisoning, endo- and exotoxicosis. Enterosorption method was proposed as a promising method for removing toxic substances from the living organisms using enterosorbents which can absorb various toxic substances of endogenous and exogenous nature in the lumen of the gastrointestinal tract. It has been proposed to use polymer-containing enterosorbents for eliminating of heavy metals from the organism. The purpose of this research was to synthesize a quaternized derivative of chitosan, specifically N-(2-hydroxybenzyl)-N-ethyl-N-methyl chitosan chloride (Q-CHS). The synthesis of Q-CHS involved the formation of a Schiff base, followed by the quaternization of the amino group of chitosan (CHS). The structures of both pure CHS and quaternized CHS were studied using various physico-chemical methods, including FTIR, NMR, XRD, SEM, DSC and TGA analyses in order to determine the structure and confirm the formation of the final product., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Mixtures containing β-glucans were extracted from barley, under both mild and high alkaline conditions, to prepare biodegradable films (MA and HA, respectively), as natural dressings with intrinsic therapeutic properties. An in-depth characterization was performed to evaluate the impact of mild and high alkaline conditions on chemical, physicochemical, and biological features for potential use in wound treatments. Both MA and HA films exhibited a good ability to absorb water and simulate wound fluid, which helps maintain optimal tissue hydration. Moreover, their oxygen permeability (147.6 and 16.4 cm 3  × μm/m 2  × 24 h × Pa × 10 7 , respectively) appeared adequate for the intended application. Biocompatibility tests showed that the films do not harm human dermal fibroblasts. Impressively, they promote cell attachment and growth, with MA having a stronger effect due to its higher β-glucan content. Furthermore, MA films can modulate macrophage behaviour in an inflamed microenvironment, reducing oxidative stress and pro-inflammatory cytokines, while simultaneously increasing levels of anti-inflammatory cytokines. In a scratch test, HA films allowed for faster fibroblast migration within the first 16 h compared to MA. Overall, this study demonstrates that developing β-glucan based films from barley, through a sustainable and cost-effective process, holds great promise for skin applications. These films exhibit significant potential to promote wound healing and modulate inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In recent decades, ionic liquids (ILs) have garnered research interest for their noteworthy properties, such as thermal stability, low or no flammability, and negligible vapour pressure. Moreover, their tunability offers limitless opportunities to design ILs with properties suitable for applications in many industrial fields. This study aims to synthetise two series of methylimidazolium ILs bearing long alkyl chain in their cations (C9, C10, C12, C14, C16, C18, C20) and with tetrafluoroborate (BF 4 ) and the 1,3-dimethyl-5-sulfoisophthalate (DMSIP) as counter ions. The ILs were characterised using 1 H-NMR and MALDI-TOF, and their thermal behaviour was investigated through DSC and TGA. Additionally, the antimicrobial, anticancer, and cytotoxic activities of the ILs were analysed. Moreover, the most promising ILs were incorporated at different concentrations (0.5, 1, 5 wt%) into polyvinyl chloride (PVC) by solvent casting to obtain antimicrobial blend films. The thermal properties and stability of the resulting PVC/IL films, along with their hydrophobicity/hydrophilicity, IL surface distribution, and release, were studied using DSC and TGA, contact angle (CA), SEM, and UV-vis spectrometry, respectively. Furthermore, the antimicrobial and cytotoxic properties of blends were analysed. The in vitro results demonstrated that the antimicrobial and antitumor activities of pure ILs against t Listeria monocytogenes , Escherichia coli , Pseudomonas fluorescens strains, and the breast cancer cell line (MCF7), respectively, were mainly dependent on their structure. These activities were higher in the series containing the BF 4 anion and increased with the increase in the methylimidazolium cation alkyl chain length. However, the elongation of the alkyl chain beyond C16 induced a decrease in antimicrobial activity, indicating a cut-off effect. A similar trend was also observed in terms of in vitro biocompatibility. The loading of both the series of ILs into the PVC matrix did not affect the thermal stability of PVC blend films. However, their T onset decreased with increased IL concentration and alkyl chain length. Similarly, both the series of PVC/IL films became more hydrophilic with increasing IL concentration and alkyl chain. The loading of ILs at 5% concentration led to considerable IL accumulation on the blend film surfaces (as observed in SEM images) and, subsequently, their higher release. The biocompatibility assessment with healthy human dermal fibroblast (HDF) cells and the investigation of antitumoral properties unveiled promising pharmacological characteristics. These findings provide strong support for the potential utilisation of ILs in biomedical applications, especially in the context of cancer therapy and as antibacterial agents to address the challenge of antibiotic resistance. Furthermore, the unique properties of the PVC/IL films make them versatile materials for advancing healthcare technologies, from drug delivery to tissue engineering and antimicrobial coatings to diagnostic devices.

Injectable bone substitutes (IBSs) represent a compelling choice for bone tissue regeneration, as they can be exploited to optimally fill complex bone defects in a minimally invasive manner. In this context, in situ gelling methylcellulose (MC) hydrogels may be engineered to be free-flowing injectable solutions at room temperature and gels upon exposure to body temperature. Moreover, incorporating a suitable inorganic phase can further enhance the mechanical properties of MC hydrogels and promote mineralization, thus assisting early cell adhesion to the hydrogel and effectively guiding bone tissue regeneration. In this work, thermo-responsive IBSs were designed selecting MC as the organic matrix and calcium phosphate (CaP) or CaP modified with graphene oxide (CaPGO) as the inorganic component. The resulting biocomposites displayed a transition temperature around body temperature, preserved injectability even after loading with the inorganic components, and exhibited adequate retention on an ex vivo calf femoral bone defect model. The addition of CaP and CaPGO promoted the in vitro mineralization process already 14 days after immersion in simulated body fluid. Interestingly, combined X-ray diffraction and solid state nuclear magnetic resonance characterizations revealed that the formed biomimetic phase was constituted by crystalline hydroxyapatite and amorphous calcium phosphate. In vitro biological characterization revealed the beneficial impact of CaP and CaPGO, indicating their potential in promoting cell adhesion, proliferation and osteogenic differentiation. Remarkably, the addition of GO, which is very attractive for its bioactive properties, did not negatively affect the injectability of the hydrogel nor the mineralization process, but had a positive impact on cell growth and osteogenic differentiation on both pre-differentiated and undifferentiated cells. Overall, the proposed formulations represent potential candidates for use as IBSs for application in bone regeneration both under physiological and pathological conditions.

Recently, the term theragenerative has been proposed for biomaterials capable of inducing therapeutic approaches followed by repairing/regenerating the tissue/organ. This study is focused on the design of a new theragenerative nanocomposite composed of an amphiphilic non-ionic surfactant (Pluronic F127), bioactive glass (BG), and black phosphorus (BP). The nanocomposite was prepared through a two-step synthetic strategy, including a microwave treatment that turned BP nanosheets (BPNS) into quantum dots (BPQDs) with 5 ± 2 nm dimensions in situ . The effects of surfactant and microwave treatment were assessed in vitro : the surfactant distributes the ions homogenously throughout the composite and the microwave treatment chemically stabilizes the composite. The presence of BP enhanced bioactivity and promoted calcium phosphate formation in simulated body fluid. The inherent anticancer activity of BP-containing nanocomposites was tested against osteosarcoma cells in vitro , finding that 150 μg mL -1 was the lowest concentration which prevented the proliferation of SAOS-2 cells, while the counterpart without BP did not affect the cell growth rate. Moreover, the apoptosis pathways were evaluated and a mechanism of action was proposed. NIR irradiation was applied to induce further proliferation suppression on SAOS-2 cells through hyperthermia. The inhibitory effects of bare BP nanomaterials and nanocomposites on the migration and invasion of bone cancer, breast cancer, and prostate cancer cells were assessed in vitro to determine the anticancer potential of nanomaterials against primary and secondary bone cancers. The regenerative behavior of the nanocomposites was tested with healthy osteoblasts and human mesenchymal stem cells; the BPQDs-incorporated nanocomposite significantly promoted the proliferation of osteoblast cells and induced the osteogenic differentiation of stem cells. This study introduces a new multifunctional theragenerative platform with promising potential for simultaneous bone cancer therapy and regeneration., Competing Interests: The authors have declared that there is no conflict of interest., (© 2024 The Authors.)

The journey of ceramics in medicine has been synchronized with an evolution from the first generation-alumina, zirconia, etc.-to the third -3D scaffolds. There is an up-and-coming member called oxygen-deficient or colored bioceramics, which have recently found their way through biomedical applications. The oxygen vacancy steers the light absorption toward visible and near infrared regions, making the colored bioceramics multifunctional-therapeutic, diagnostic, and regenerative. Oxygen-deficient bioceramics are capable of turning light into heat and reactive oxygen species for photothermal and photodynamic therapies, respectively, and concomitantly yield infrared and photoacoustic images. Different types of oxygen-deficient bioceramics have been recently developed through various synthesis routes. Some of them like TiO 2- x , MoO 3- x , and WO x have been more investigated for biomedical applications, whereas the rest have yet to be scrutinized. The most prominent advantage of these bioceramics over the other biomaterials is their multifunctionality endowed with a change in the microstructure. There are some challenges ahead of this category discussed at the end of the present review. By shedding light on this recently born bioceramics subcategory, it is believed that the field will undergo a big step further as these platforms are naturally multifunctional., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Redox-active nano-biointerfaces are gaining weight in the field of regenerative medicine since they can act as enzymes in regulating physiological processes and enabling cell homeostasis, as well as the defense against pathogen aggression. In particular, cerium oxide nanoparticles (CeO 2 NPs) stand as intriguing enzyme-mimicking nanoplatforms, owing to the reversible Ce +3 /Ce +4 surface oxidation state. Moreover, surface functionalization leads to higher catalytic activity and selectivity, as well as more tunable enzyme-mimicking performances. Conjugation with melanin is an adequate strategy to boost and enrich CeO 2 NPs biological features, because of melanin redox properties accounting for intrinsic antioxidant, antimicrobial and anti-inflammatory power. Herein, hybrid Melanin/CeO 2 nanostructures were designed by simply coating the metal-oxide nanoparticles with melanin chains, obtained in-situ through ligand-to-metal charge transfer mechanism, according to a bioinspired approach. Obtained hybrid nanostructures underwent detailed physico-chemical characterization. Morphological and textural features were investigated through TEM, XRD and N 2 physisorption. The nature of nanoparticle-melanin interaction was analyzed through FTIR, UV-vis and EPR spectroscopy. Melanin-coated hybrid nanostructures exhibited a relevant antioxidant activity, confirmed by a powerful quenching effect for DPPH radical, reaching 81 % inhibition at 33 μg/mL. A promising anti-inflammatory efficacy of the melanin-coated hybrid nanostructures was validated through a significant inhibition of BSA denaturation after 3 h. Meanwhile, the enzyme-mimicking activity was corroborated by a prolonged peroxidase activity after 8 h at 100 μg/mL and a relevant catalase-like action, by halving the H 2 O 2 level in 30 min at 50 μg/mL. Antimicrobial assays attested that conjugation with melanin dramatically boosted CeO 2 biocide activity against both Gram (-) and Gram (+) strains. Cytocompatibility tests demonstrated that the melanin coating not only enhanced the CeO 2 nanostructures biomimicry, resulting in improved cell viability for human dermal fibroblast cells (HDFs), but mostly they proved that Melanin-CeO 2 NPs were able to control the oxidative stress, modulating the production of nitrite and reactive oxygen species (ROS) levels in HDFs, under physiological conditions. Such remarkable outcomes make hybrid melanin-CeO 2 nanozymes, promising redox-active interfaces for regenerative medicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The species of Candida present good capability to form fungal biofilms on polymeric surfaces and are related to several human diseases since many of the employed medical devices are designed using polymers, especially high-density polyethylene (HDPE). Herein, HDPE films containing 0; 0.125; 0.250 or 0.500 wt% of 1-hexadecyl-3-methylimidazolium chloride (C 16 MImCl) or its analog 1-hexadecyl-3-methylimidazolium methanesulfonate (C 16 MImMeS) were obtained by melt blending and posteriorly mechanically pressurized into films. This approach resulted in more flexible and less brittle films, which impeded the Candida albicans, C. parapsilosis , and C. tropicalis biofilm formation on their surfaces. The employed imidazolium salt (IS) concentrations did not present any significant cytotoxic effect, and the good cell adhesion/proliferation of human mesenchymal stem cells on the HDPE-IS films indicated good biocompatibility. These outcomes combined with the absence of microscopic lesions in pig skin after contact with HDPE-IS films demonstrated their potential as biomaterials for the development of effective medical device tools that reduce the risk of fungal infections.

Spinal cord injury (SCI) is characterized by neuroinflammatory processes that are marked by an uncontrolled activation of microglia, which directly damages neurons. Natural and synthetic melanins represent an effective tool to treat neuroinflammation because they possess immunomodulatory properties. Here, the main objective was to evaluate the effect of eumelanin-coated poly(lactic acid) (EU@PLA) aligned microfibers on in vitro model of neuroinflammation related to spinal cord injury in terms of inflammatory mediators' modulation. Aligned fibers were chosen to provide physical cues to guide axonal growth in a specific direction thus restoring the synaptic connection. Eumelanin decorated PLA electrospun substrates were produced combining electrospinning, spin coating and solid-state polymerization processes (oxidative coupling under oxygen atmosphere). Biological response in terms of antioxidant and anti-inflammatory activity was analyzed on an in vitro model of neuroinflammation [microglial cells stimulated with lipopolysaccharide (LPS)]. Cell morphology and EU@PLA mechanism of action, in terms of toll-like receptor-4 (TLR-4) involvement were assessed. The results show that EU@PLA fibers were able to decrease reactive oxygen species, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-кB) expression >50 % compared to PLA + LPS and interleukin 6 (IL-6) secretion about 20 %. Finally, the mechanism of action of EU@PLA in microglia was found to be dependent on the TLR-4 signaling. Protein expression analysis revealed a decreased in TLR-4 production induced by LPS stimulation in presence of EU@PLA. Overall, our results show that EU@PLA represents an innovative and effective strategy for the control of inflammatory response in central nervous system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Gellan gum (GG) was chemically modified with methacrylic moieties to produce a photocrosslinkable biomaterial ink, hereinafter called methacrylated GG (GGMA), with improved physico-chemical properties, mechanical behavior and stability under physiological conditions. Afterwards, GGMA was functionalized by incorporating two different bioactive compounds, a naturally derived eumelanin extracted from the black soldier fly (BSF-Eumel), or hydroxyapatite nanoparticles (HAp), synthesized by the sol-gel method. Different ink formulations based on GGMA (2 and 4% ( w / v )), BSF-Eumel, at a selected concentration (0.3125 mg/mL), or HAp (10 and 30% w HAp /w GGMA ) were developed and processed by three-dimensional (3D) printing. All the functionalized GGMA-based ink formulations allowed obtaining 3D-printed GGMA-based scaffolds with a well-organized structure. For both bioactive signals, the scaffolds with the highest GGMA concentration (4% ( w / v )) and the highest percentage of infill (45%) showed the best performances in terms of morphological and mechanical properties. Indeed, these scaffolds showed a good structural integrity over 28 days. Given the presence of negatively charged groups along the eumelanin backbone, scaffolds consisting of GGMA/BSF-Eumel demonstrated a higher stability. From a mechanical point of view, GGMA/BSF-Eumel scaffolds exhibited values of storage modulus similar to those of GGMA ones, while the inclusion of HAp at 30% (w HAp /w GGMA ) led to a storage modulus of 32.5 kPa, 3.5-fold greater than neat GGMA. In vitro studies proved the capability of the bioactivated 3D-printed scaffolds to support 7F2 osteoblast cell growth and differentiation. BSF-Eumel and HAp triggered a different time-dependent physiological response in the osteoblasts. Specifically, while the ink with BSF-Eumel acted as a stimulus towards cell proliferation, reaching the highest value at 14 days, a higher expression of alkaline phosphatase activity was detected for scaffolds consisting of GGMA and HAp. The overall findings demonstrated the possible use of these biomaterial inks for 3D-printed bone tissue-engineered scaffolds.

Graphene oxide (GO) and its reduced form (rGO) have recently attracted a fascinating interest due to their physico-chemical properties, which have opened up new and interesting opportunities in a wide range of biomedical applications, such as wound healing. It is worth noting that GO and rGO may offer a convenient access to its ready dispersion within various polymeric matrices (such as cellulose and its derivative forms), owing to their large surface area, based on a carbon skeleton with many functional groups (i.e., hydroxyl, carboxyl, epoxy bridge, and carbonyl moieties). This results in new synergic properties due to the presence of both components (GO or rGO and polymers), acting at different length-scales. Furthermore, they have shown efficient antimicrobial and angiogenic properties, mostly related to the intracellular formation of reactive oxygen species (ROS), which are advantageous in wound care management. For this reason, GO or rGO integration in cellulose-based matrixes have allowed for designing highly advanced multifunctional hybrid nanocomposites with tailored properties. The current review aims to discuss a potential relationship between structural and physico-chemical properties (i.e., size, edge density, surface chemistry, hydrophilicity) of the nanocomposites with antimicrobials and angiogenic mechanisms that synergically influence the wound healing phenomenon, by paying particular attention to recent findings of GO or rGO/cellulose nanocomposites. Accordingly, after providing a general overview of cellulose and its derivatives, the production methods used for GO and rGO synthesis, the mechanisms that guide antimicrobial and angiogenic processes of tissue repair, as well as the most recent and remarkable outcomes on GO/cellulose scaffolds in wound healing applications, will be presented.

Materials that are able to produce free radicals have gained increasing attention for environmental and biomedical purposes. Free radicals, such as the superoxide anion (O 2 •- ), act as secondary messengers in many physiological pathways, such as cell survival. Therefore, the production of free radicals over physiological levels has been exploited in the treatment of different types of cancer, including osteosarcoma (OS). In most cases, the production of reactive oxygen species (ROS) by materials is light-induced and requires the use of chemical photosensitisers, making it difficult and expensive. Here, for the first time, we propose photoluminescent hybrid ZrO 2 -acetylacetonate nanoparticles (ZrO 2 -acac NPs) that are capable of generating O 2 •- without light activation as an adjuvant for the treatment of OS. To increase the uptake and ROS generation in cancer cells, we modify the surface of ZrO 2 -acac NPs with hyaluronic acid (HA), which recognizes and binds to the surface antigen CD44 overexpressed on OS cells. Since these nanoparticles emit in the visible range, their uptake into cancer cells can be followed by a label-free approach. Overall, we show that the generation of O 2 •- is toxic to OS cells and can be used as an adjuvant treatment to increase the efficacy of conventional drugs.

Hybrid bone substitute made up of a 3D printed polyetheretherketone (PEEK) scaffold coated with methacrylated hyaluronic acid (MeHA)-hydroxyapatite (HAp) hydrogel is the objective of the present work. Development and characterization of the scaffold and of the MeHA-HAp after its infiltration and UV photocrosslinking have been followed by analyses of its biological properties using human mesenchymal stem cells (MSCs). Interconnected porous PEEK matrices were produced by fused deposition modeling (FDM) characterized by a reticular pattern with 0°/90° raster orientation and square pores. In parallel, a MeHA-HAp slurry has been synthesized and infiltrated in the PEEK scaffolds. The mechanical properties of the coated and pure PEEK scaffold have been evaluated, showing that the inclusion of MeHA-HAp into the lattice geometry did not significantly change the strength of the PEEK structure with Young's modulus of 1034.9 ± 126.1 MPa and 1020.0 ± 63.7 MPa for PEEK and PEEK-MeHA-HAp scaffolds, respectively. Human MSCs were seeded on bare and coated scaffolds and cultured for up to 28 days to determine the adhesion, proliferation, migration and osteogenic differentiation. In vitro results showed that the MeHA-HAp coating promotes MSCs adhesion and proliferation and contributes to osteogenic differentiation and extracellular matrix mineralization. This study provides an efficient solution for the development of a scaffold combining the great mechanical performances of PEEK with the bioactive properties of MeHA and HAp, having high potential for translational clinical applications.

An optimized extraction protocol for eumelanins from black soldier flies (BSF-Eumel) allows an in-depth study of natural eumelanin pigments, which are a valuable tool for the design and fabrication of sustainable scaffolds. Here, water-soluble BSF-Eumel sub-micrometer colloidal particles were used as bioactive signals for developing a composite biomaterial ink for scaffold preparation. For this purpose, BSF-Eumel was characterized both chemically and morphologically; moreover, biological studies were carried out to investigate the dose-dependent cell viability and its influence on human mesenchymal stem cells (hMSCs), with the aim of validating suitable protocols and to find an optimal working concentration for eumelanin-based scaffold preparation. As proof of concept, 3D printed scaffolds based on methacrylated hyaluronic acid (MEHA) and BSF-Eumel were successfully produced. The scaffolds with and without BSF-Eumel were characterized in terms of their physico-chemical, mechanical and biological behaviours. The results showed that MEHA/BSF-Eumel scaffolds had similar storage modulus values to MEHA scaffolds. In terms of swelling ratio and stability, these scaffolds were able to retain their structure without significant changes over 21 days. Biological investigations demonstrated the ability of the bioactivated scaffolds to support the adhesion, proliferation and osteogenic differentiation of human mesenchymal stem cells.

Black phosphorus nanosheets (2D BP) are emerging as very promising, highly selective chemotherapeutic agents due to their fast degradation in the intracellular matrix of cancer cells. Here, optical diffraction tomography (ODT) and Raman spectroscopy were exploited as a powerful label-free approach to achieve integrated insights into the processes accompanying the administration of exfoliated 2D BP flakes in human prostatic adenocarcinoma and normal human prostate epithelial cells. Our ODT experiments provided unambiguous visualization of the 2D BP internalization in cancer cells and the morphological modifications of those cells in the apoptotic phase. The cellular internalization and damaging occurred, respectively, 18 h and 36-48 h after the 2D BP administration. Changes in the chemical properties of the internalized 2D BP flakes were monitored by Raman spectroscopy. Interestingly, a fast oxidation process of the 2D BP flakes was activated in the intracellular matrix of the cancer cells after 24 h of incubation. This was in sharp contrast to the low 2D BP uptake and minimal chemical changes observed in the normal cells. Along with the understanding of the 2D BP fate in the cancer cells, the proposed label-free morpho-molecular approach offers a powerful, rapid tool to study the pharmacokinetic properties of engineered nanomaterials in preclinical research.

Considerable attention has been given to the use of chitosan (CS)-based materials reinforced with inorganic bioactive signals such as hydroxyapatite (HA) to treat bone defects and tissue loss. It is well known that CS/HA based materials possess minimal foreign body reactions, good biocompatibility, controlled biodegradability and antibacterial property. Herein, the bioactivity of these composite systems was analyzed on in vitro bone cell models for their applications in the field of bone tissue engineering (BTE). The combination of sol-gel approach and freeze-drying technology was used to obtain CS/HA scaffolds with three-dimensional (3D) porous structure suitable for cell in-growth. Specifically, our aim was to investigate the influence of bioactive composite scaffolds on cellular behavior in terms of osteoinductivity and anti-inflammatory effects for treating bone defects. The results obtained have demonstrated that by increasing inorganic component concentration, CS/HA (60 and 70% v/v) scaffolds induced a good biological response in terms of osteogenic differentiation of human mesenchymal stem cells (hMSC) towards osteoblast phenotype. Furthermore, the scaffolds with higher concentration of inorganic fillers are able to modulate the production of pro-inflammatory (TGF-β) and anti-inflammatory (IL-4, IL-10) cytokines. Our results highlight the possibility of achieving smart CS/HA based composites able to promote a great osteogenic differentiation of hMSC by increasing the amount of HA nanoparticles used as bioactive inorganic signal. Contemporarily, these materials allow avoiding the induction of a pro-inflammatory response in bone implant site., (© 2021 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Cancer is one of the top life-threatening dangers to the human survival, accounting for over 10 million deaths per year. Bioactive glasses have developed dramatically since their discovery 50 years ago, with applications that include therapeutics as well as diagnostics. A new system within the bioactive glass family, mesoporous bioactive glasses (MBGs), has evolved into a multifunctional platform, thanks to MBGs easy-to-functionalize nature and tailorable textural properties-surface area, pore size, and pore volume. Although MBGs have yet to meet their potential in tumor treatment and imaging in practice, recently research has shed light on the distinguished MBGs capabilities as promising theranostic systems for cancer imaging and therapy. This review presents research progress in the field of MBG applications in cancer diagnosis and therapy, including synthesis of MBGs, mechanistic overview of MBGs application in tumor diagnosis and drug monitoring, applications of MBGs in cancer therapy ( particularly, targeted delivery and stimuli-responsive nanoplatforms), and immunological profile of MBG-based nanodevices in reference to the development of novel cancer therapeutics., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Magnesium (Mg)- and silicon (Si)-substituted hydroxyapatite (HA) scaffolds were synthesized using the sponge replica method. The influence of Mg 2+ and SiO 4 ion substitution on the microstructural, mechanical and biological properties of HA scaffolds was evaluated. All synthesized scaffolds exhibited porosity >92%, with interconnected pores and pore sizes ranging between 200 and 800 μm. X-ray diffraction analysis showed that β-TCP was formed in the case of Mg substitution. X-ray fluorescence mapping showed a homogeneous distribution of Mg and Si ions in the respective scaffolds. Compared to the pure HA scaffold, a reduced grain size was observed in the Mg- and Si-substituted scaffolds, which greatly influenced the mechanical properties of the scaffolds. Mechanical tests revealed better performance in HA-Mg (0.44 ± 0.05 MPa), HA-Si (0.64 ± 0.02 MPa) and HA-MgSi (0.53 ± 0.01 MPa) samples compared to pure HA (0.2 ± 0.01 MPa). During biodegradability tests in Tris-HCl, slight weight loss and a substantial reduction in mechanical performances of the scaffolds were observed. Cell proliferation determined by the MTT assay using hBMSC showed that all scaffolds were biocompatible, and the HA-MgSi scaffold seemed the most effective for cell adhesion and proliferation. Furthermore, ALP activity and osteogenic marker expression analysis revealed the ability of HA-Si and HA-MgSi scaffolds to promote osteoblast differentiation.4- ion substitution on the microstructural, mechanical and biological properties of HA scaffolds was evaluated. All synthesized scaffolds exhibited porosity >92%, with interconnected pores and pore sizes ranging between 200 and 800 μm. X-ray diffraction analysis showed that β-TCP was formed in the case of Mg substitution. X-ray fluorescence mapping showed a homogeneous distribution of Mg and Si ions in the respective scaffolds. Compared to the pure HA scaffold, a reduced grain size was observed in the Mg- and Si-substituted scaffolds, which greatly influenced the mechanical properties of the scaffolds. Mechanical tests revealed better performance in HA-Mg (0.44 ± 0.05 MPa), HA-Si (0.64 ± 0.02 MPa) and HA-MgSi (0.53 ± 0.01 MPa) samples compared to pure HA (0.2 ± 0.01 MPa). During biodegradability tests in Tris-HCl, slight weight loss and a substantial reduction in mechanical performances of the scaffolds were observed. Cell proliferation determined by the MTT assay using hBMSC showed that all scaffolds were biocompatible, and the HA-MgSi scaffold seemed the most effective for cell adhesion and proliferation. Furthermore, ALP activity and osteogenic marker expression analysis revealed the ability of HA-Si and HA-MgSi scaffolds to promote osteoblast differentiation.

Cellulose represents a low cost, abundant, and renewable polysaccharide with great versatility; it has a hierarchical structure composed of nanofibers with high aspect ratio (3-4 nm wide, hundreds of μm long). TEMPO-mediated oxidation represents one of the most diffused methods to obtain cellulose nanofibers (CNFs): It is possible to obtain physically crosslinked hydrogels by means of divalent cation addition. The presence of inorganic components, such as calcium phosphates (CaP), can improve not only their mechanical properties but also the bioactivity of the gels. The aim of this work is to design and characterize a TEMPO-oxidized cellulose nanofibers (TOCNFs) injectable hydrogel embedded with inorganic particles, CaP and CaP-GO, for bone tissue regeneration. Inorganic particles act as physical crosslinkers, as proven by rheological characterization, which reported an increase in mechanical properties. The average load value registered in injection tests was in the range of 1.5-4.4 N, far below 30 N, considered a reasonable injection force upper limit. Samples were stable for up to 28 days and both CaP and CaP-GO accelerate mineralization as suggested by SEM and XRD analysis. No cytotoxic effects were shown on SAOS-2 cells cultured with eluates. This work demonstrated that the physicochemical properties of TOCNFs-based dispersions could be enhanced and modulated through the addition of the inorganic phases, maintaining the injectability and bioactivity of the hydrogels.

Electrospun porous bone scaffolds are known to imitate the extracellular matrix very well and provide an environment through which the tissue formation is enhanced. Although polymeric scaffolds have a great potential in bone tissue regeneration, their weak bioactivity (bone bonding ability) and mechanical properties have left room for improvement. Therefore, the present study focused on the developing a ternary multifunctional platform composed of polycaprolactone (PCL)/silk fibroin (SF)/Zn-substituted Mg 2 SiO 4 nanoparticles for bone tissue regeneration. This study is composed of two connected sections including synthesis and characterization of Mg (2-x) Zn x SiO 4 , x = 0, 0.5, 1, 1.5, 2 through surfactant-assisted sol-gel technique followed by incorporation of the nanoparticles into PCL/SF hybrid scaffold via electrospinning technique. The weight ratios of polymers and ceramic nanoparticles were optimized to reach desirable textural-porosity, pore size, and fiber diameter-and mechanical properties. Having optimized the ternary scaffold, it was then undergone different physical, chemical, and biological tests in vitro. A precise comparison study between the ternary (PCL/SF/ceramic nanoparticles), binary (PCL/SF), and pure PCL was made to shed light on the effect of each composition on the applicability of ternary scaffold. The overall results confirmed that the Mg 1 Zn 1 SiO 4 nanoparticles-incorporated PCL/SF scaffold with fluorescence property was the one yielding the highest Young's modulus and desirable textural properties. The ternary scaffold showed improved biological properties making it a promising candidate for further studies towards bone tissue regeneration., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Bone cancer is a demanding challenge for contemporary medicine due to its high frequency of presentation and significant heterogeneity of malignant lesions developing within the bone. To date, available treatments are rarely curative and are primarily aimed at prolonging patients' survival and ameliorating their quality of life. Furthermore, both pharmacological and surgical therapies are aggravated by a consistent burden of adverse events and subsequent disability due to the loss of healthy bone structural and functional properties. Therefore, great research efforts are being made to develop innovative biomaterials able to selectively inhibit bone cancer progression while reducing the loss of bone structural properties secondary to local tissue invasion. In this review, we describe the state of the art of innovative biomaterials for the treatment of bone cancer. Along with physiological bone remodeling, the development of bone metastasis and osteosarcoma will be depicted. Subsequently, recent advances on nanocarrier-based drug delivery systems, as well as the application of novel, multifunctional biomaterials for the treatment of bone cancer will be discussed. Eventually, actual limitations and promising future perspectives regarding the employment of such approaches in the clinical scenario will be debated.