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Mesoporous silica nanoparticles were synthesized using a microemulsion-assisted sol-gel method, and calcium, gallium or a combination of both, were used as dopants. The influence of these metallic ions on the physicochemical properties of the nanoparticles was investigated by scanning and transmission electron microscopy, as well as N 2 adsorption-desorption methods. The presence of calcium had a significant impact on the morphology and textural features of the nanoparticles. The addition of calcium increased the average diameter of the nanoparticles from 80 nm to 150 nm, while decreasing their specific surface area from 972 m 2 /g to 344 m 2 /g. The nanoparticles of all compositions were spheroidal, with a disordered mesoporous structure. An ion release study in cell culture medium demonstrated that gallium was released from the nanoparticles in a sustained manner. In direct contact with concentrations of up to 100 μg/mL of the nanoparticles, gallium-containing nanoparticles did not exhibit cytotoxicity towards pre-osteoblast MC3T3-E1 cells. Moreover, in vitro cell culture tests revealed that the addition of gallium to the nanoparticles enhanced osteogenic activity. Simultaneously, the nanoparticles disrupted the osteoclast differentiation of RAW 264.7 macrophage cells. These findings suggest that gallium-containing nanoparticles possess favorable physicochemical properties and biological characteristics, making them promising candidates for applications in bone tissue regeneration, particularly for unphysiological or pathological conditions such as osteoporosis., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Three-dimensional (3D) printing allows precise manufacturing of bone scaffolds for patient-specific applications and is one of the most recently developed and implemented technologies. In this study, bilayer and multimaterial alginate dialdehyde-gelatin (ADA-GEL) scaffolds incorporating polydopamine (PDA)/SiO 2 -CaO nanoparticle complexes were 3D printed using a pneumatic extrusion-based 3D printing technology and further modified on the surface with bovine serum albumin (BSA) for application in bone regeneration. The morphology, chemistry, and in vitro bioactivity of PDA/SiO 2 -CaO nanoparticle complexes were characterized (n = 3) and compared with those of mesoporous SiO 2 -CaO nanoparticles. Successful deposition of the PDA layer on the surface of the SiO 2 -CaO nanoparticles allowed better dispersion in a liquid medium and showed enhanced bioactivity. Rheological studies (n = 3) of ADA-GEL inks consisting of PDA/SiO 2 -CaO nanoparticle complexes showed results that may indicate better injectability and printability behavior compared to ADA-GEL inks incorporating unmodified nanoparticles. Microscopic observations of 3D printed scaffolds revealed that PDA/SiO 2 -CaO nanoparticle complexes introduced additional topography onto the surface of 3D printed scaffolds. Additionally, the modified scaffolds were mechanically stable and elastic, closely mimicking the properties of natural bone. Furthermore, protein-coated bilayer scaffolds displayed controllable absorption and biodegradation, enhanced bioactivity, MC3T3-E1 cell adhesion, proliferation, and higher alkaline phosphatase (ALP) activity (n = 3) compared to unmodified scaffolds. Consequently, the present results confirm that ADA-GEL scaffolds incorporating PDA/SiO 2 -CaO nanoparticle complexes modified with BSA offer a promising approach for bone regeneration applications., Competing Interests: Declaration of competing interest The authors whose names are listed certify that they have no affiliations with or involvement in any organization or entity with any financial or non-financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The present work focuses on developing 5% w/v oxidized alginate (alginate di aldehyde, ADA)-7.5% w/v gelatin (GEL) hydrogels incorporating 0.25% w/v silk fibroin (SF) and loaded with 0.3% w/v Cu-Ag doped mesoporous bioactive glass nanoparticles (Cu-Ag MBGNs). The microstructural, mechanical, and biological properties of the composite hydrogels were characterized in detail. The porous microstructure of the developed ADA-GEL based hydrogels was confirmed by scanning electron microscopy, while the presence of Cu-Ag MBGNs in the synthesized hydrogels was determined using energy dispersive x-ray spectroscopy. The incorporation of 0.3% w/v Cu-Ag MBGNs reduced the mechanical properties of the synthesized hydrogels, as investigated using micro-tensile testing. The synthesized ADA-GEL loaded with 0.25% w/v SF and 0.3% w/v Cu-Ag MBGNs showed a potent antibacterial effect against Escherichia coli and Staphylococcus aureus . Cellular studies using the NIH3T3-E1 fibroblast cell line confirmed that ADA-GEL films incorporated with 0.3% w/v Cu-Ag MBGNs exhibited promising cellular viability as compared to pure ADA-GEL (determined by WST-8 assay). The addition of SF improved the biocompatibility, degradation rate, moisturizing effects, and stretchability of the developed hydrogels, as determined in vitro . Such multimaterial hydrogels can stimulate angiogenesis and exhibit desirable antibacterial properties. Therefore further ( in vivo ) tests are justified to assess the hydrogels' potential for wound dressing and skin tissue healing applications., (Creative Commons Attribution license.)

Binary SiO 2 -CaO mesoporous bioactive glass nanoparticles (MBGNs) are multifunctional biomaterials able to promote osteogenic, angiogenic, and immunomodulatory activities. MBGNs have been applied in a variety of tissue regeneration strategies. However, MBGNs lack strong antibacterial activity and current strategies (loading of antibacterial ions or antibiotics) toward enhanced antibacterial activity may cause cytotoxicity or antibiotic resistance. Here we engineered MBGNs using bacteriophages (phages) to enhance the antibacterial activity. Salmonella Typhimurium (S. T) phage PFPV25.1 that can infect Salmonella enterica serovar Typhimurium strain LT2 was used as a model phage to engineer MBGNs. MBGNs were first modified with amine groups to enhance the affinity between phages and MBGNs surfaces. Afterward, the physicochemical and antibacterial activity of phage-engineered MBGNs was evaluated. The results showed that S. T phage PFPV25.1 was successfully bound onto MBGNs surfaces without losing their bioactivity. A higher quantity of phages could be bounded onto amine-functionalized MBGNs than onto non-functionalized MBGNs. Phages on amine-functionalized MBGNs exhibited higher antibacterial activity. The stability test showed that phages could remain on amine-functionalized MBGNs for over 28 days. This work provides valuable information on developing phage-modified MBGNs as a new and effective antibacterial system for biomedical applications., 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.)

Treating bone infections and ensuring bone repair is one of the greatest global challenges of modern orthopedics, made complex by antimicrobial resistance (AMR) risks due to long-term antibiotic treatment and debilitating large bone defects following infected tissue removal. An ideal multi-faceted solution would will eradicate bacterial infection without long-term antibiotic use, simultaneously stimulating osteogenesis and angiogenesis. Here, a multifunctional collagen-based scaffold that addresses these needs by leveraging the potential of antibiotic-free antimicrobial nanoparticles (copper-doped bioactive glass, CuBG) to combat infection without contributing to AMR in conjunction with microRNA-based gene therapy (utilizing an inhibitor of microRNA-138) to stimulate both osteogenesis and angiogenesis, is developed. CuBG scaffolds reduce the attachment of gram-positive bacteria by over 80%, showcasing antimicrobial functionality. The antagomiR-138 nanoparticles induce osteogenesis of human mesenchymal stem cells in vitro and heal a large load-bearing defect in a rat femur when delivered on the scaffold. Combining both promising technologies results in a multifunctional antagomiR-138-activated CuBG scaffold inducing hMSC-mediated osteogenesis and stimulating vasculogenesis in an in vivo chick chorioallantoic membrane model. Overall, this multifunctional scaffold catalyzes killing mechanisms in bacteria while inducing bone repair through osteogenic and angiogenic coupling, making this platform a promising multi-functional strategy for treating and repairing complex bone infections., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Bioactive glass nanoparticles (BGNs) are well-recognized multifunctional biomaterials for bone tissue regeneration due to their capability to stimulate various cellular processes through released biologically active ions. Understanding the correlation between BGN composition and cellular responses is key to developing clinically usable BGN-based medical devices. This study investigated the influence of CaO content of binary SiO 2 -CaO BGNs (CaO ranging from 0 to 10 mol%) on osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and in vivo bone regeneration in zebrafish osteoporosis model. The results showed that BGNs could promote osteogenic differentiation of rBMSCs by indirectly releasing active ions or directly interacting with rBMSCs by internalization. In both situations, BGNs of a higher CaO content could promote the osteogenic differentiation of rBMSCs to a greater extent. The internalized BGNs could activate the transcription factors RUNX2 and OSX, leading to the expression of osteogenesis-related genes. The results in the zebrafish osteoporosis model indicated that the presence of BGNs of higher CaO contents could enhance bone regeneration and rescue dexamethasone-induced osteoporosis to a greater extent. These findings demonstrate that BGNs can stimulate osteogenic differentiation of rBMSCs by releasing active ions or internalization. A higher CaO content facilitates osteogenesis and bone regeneration of zebrafish as well as relieving dexamethasone-induced osteoporosis. The zebrafish osteoporosis model can be a potent tool for evaluating the in vivo bone regeneration effects of bioactive materials. STATEMENT OF SIGNIFICANCE: Bioactive glass nanoparticles (BGNs) are increasingly used as fillers of nanocomposites or as delivery platforms of active ions to regenerate bone tissue. Various studies have shown that BGNs can enhance osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by releasing active ions. However, the correlation between BGN composition and cellular responses and in vivo bone regeneration effect has still not been well investigated. Establishment of a suitable in vivo animal model for investigating this correlation is also challenging. The present study reports the influence of CaO content in binary SiO 2 -CaO BGNs on osteogenic differentiation of BMSCs extracellularly and intracellularly. This study also demonstrates the suitability of zebrafish osteoporosis model to investigate in vivo bone regeneration effect of BGNs., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest in this work., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

In the present study, we investigated commercial dental floss coated with chitosan or chitosan + mesoporous bioactive glass nanoparticles (MBGNs) in order to determine the antimicrobial and mechanical properties of the newly fabricated flosses. Whereas these coatings showed notable ability to inhibit growth of both Gram (+) and Gram (-) bacteria after 24 h, the impact was negligible at 3 h. Furthermore, the tensile strength of the floss was improved by the addition of these layers, making it more durable and effective for cleaning between teeth. We therefore propose enhanced investigations of these composites since they demonstrate enormous potential in promoting oral health., (© 2023. The Author(s).)

Multifunctional biohybrid nanofibers (NFs) that can simultaneously drive various cellular activities and confer antibacterial properties are considered desirable in producing advanced wound healing materials. In this study, a bionanohybrid formulation was processed as a NF wound dressing to stimulate the adhesion and proliferation of fibroblast and endothelial cells that play a major role in wound healing. Polyacrylonitrile (PAN) electrospun NFs were hydrolyzed using NaOH and biofunctionalized with l-carnosine (CAR), a dipeptide which could later biosynthesize zinc oxide (ZnO) nanoparticles (NPs) on the NFs surface. The morphological study verified that ZnO NPs are uniformly distributed on the surface of CAR/PAN NFs. Through EDX and XRD analysis, it was validated that the NPs are composed of ZnO and/or ZnO/Zn(OH) 2 . The presence of CAR and ZnO NPs brought about a superhydrophilicity effect and notably raised the elastic modulus and tensile strength of Zn-CAR/PAN NFs. While CAR ligands were shown to improve the viability of fibroblast (L929) and endothelial (HUVEC) cells, ZnO NPs lowered the positive impact of CAR, most likely due to their repulsive negative surface charge. A scratch assay verified that CAR/PAN NFs and Zn-CAR/PAN NFs aided HUVEC migration more than PAN NFs. Also, an antibacterial assay implied that CAR/PAN NFs and Zn-CAR/PAN NFs are significantly more effective in inhibiting Staphylococcus aureus ( S. aureus ) than neat PAN NFs are (1000 and 500%, respectively). Taken together, compared to the neat PAN NFs, CAR/PAN NFs with and without the biosynthesized ZnO NPs can support the cellular activities of relevance for wound healing and inactivate bacteria.

Exploring new approaches to realize the possibility of incorporating biologically active elements into mesoporous silicate bioactive glass nanoparticles (MBG NPs) and guaranteeing their meso- structural integrity and dimensional stability has become an attractive and interesting challenge in biomaterials science. We present a postgrafting strategy for introducing different metal elements into MBG NPs. This strategy is mediated by polydopamine (PDA) coating, achieving uniform loading of copper or copper-cobalt on the particles efficiently and ensuring the stability of MBG NPs in terms of particle size, mesoporous structure, and chemical structure. However, the PDA coating reduced the ion-binding free energy of the MBG NPs for calcium and phosphate ions, resulting in the deposition of minimal CaP clusters on the PDA@MBG NP surface when immersed for 7 days in simulated body fluid, indicating the absence of hydroxyapatite mineralization.

Electrospun scaffolds based on poly(l-lactic acid) (PLLA) with bioglass (n-BG) and zinc oxide (n-ZnO), and mixture of both, were developed to design bifunctional biomaterials with enhanced bioactive and biocidal properties. The presence of n-BG increased the fiber diameter of the pure PLA from 1.5 ± 0.3 μm to 3.0 ± 0.8 μm for 20 wt%. ZnO and the mixed nanoparticles did not significantly affect the morphology. The mechanical properties decreased with the presence of nanoparticles. Scaffolds based on PLA/n-BG promoted hydroxyapatite (HA) formation in simulated body fluid (SBF) that was inhibited with the presence of ZnO. Notably, mixed particles produced bioactivity although at longer times. The incorporation of n-ZnO produced a biocidal capacity against S. aureus in the polymeric scaffold, reaching a viability reduction of 60 % after 6 h of exposure. When both types of nanoparticles were combined, the bacterial viability reduction was 30 %. Pure PLA scaffolds and the composites with n-BG showed good ST-2 bone marrow-derived cell line viability, scaffolds with n-BG (pure or mixture) presented lower viability. Results validated the use of both n-BG and n-ZnO fillers for the development of novel bifunctional PLA-based scaffolds with both bioactive and biocidal properties for bone tissue engineering applications., 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 © 2022 Elsevier B.V. All rights reserved.)

A novel biomaterial comprising alginate dialdehyde-gelatine (ADA-GEL) hydrogel augmented by lysozyme loaded mesoporous cerium doped silica-calcia nanoparticles (Lys-Ce-MSNs) is 3D printed to create bioactive scaffolds. Lys-Ce-MSNs raise the mechanical stiffness of the hydrogel composite scaffold and induce surface apatite mineralization, when the scaffold is immersed in simulated body fluid (SBF). Moreover, the scaffolds can co-deliver bone healing (Ca and Si) and antioxidant ions (Ce), and Lys to achieve antibacterial (and potentially anticancer) properties. The nanocomposite hydrogel scaffolds can hold and deliver Lys steadily. Based on the in vitro results, the hydrogel nanocomposite containing Lys assured improved pre-osteoblast cell (MC3T3-E1) proliferation, adhesion, and differentiation, thanks to the biocompatibility of ADA-GEL, bioactivity of Ce-MSNs, and the stabilizing effect of Lys on the scaffold structure. On the other hand, the proliferation level of MG63 osteosarcoma cells decreased, likely due to the effect of Lys. Last but not least, cooperatively, alongside gentamicin (GEN), Lys brought about a proper antibacterial efficiency to the hydrogel nanocomposite scaffold against gram-positive and gram-negative bacteria. Taken together, ADA-GEL/Lys-Ce-MSN nanocomposite holds great promise for 3D printing of multifunctional hydrogel bone tissue engineering (BTE) scaffolds, able to induce bone regeneration, address infection, and potentially inhibit tumor formation and growth., (© 2022 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.)

Increasing research has incorporated bioactive glass nanoparticles (BGN) and electric field (EF) stimulation for bone tissue engineering and regeneration applications. However, their interplay and the effects of different EF stimulation regimes on osteogenic differentiation of human mesenchymal stem cells (hMSC) are less investigated. In this study, we introduced EF with negligible magnetic field strength through a well-characterized transformer-like coupling (TLC) system, and applied EF disrupted (4/4) or consecutive (12/12) regime on type I collagen (Col) coatings with/without BGN over 28 days. Additionally, dexamethasone was excluded to enable an accurate interpretation of BGN and EF in supporting osteogenic differentiation. Here, we demonstrated the influences of BGN and EF on collagen topography and maintaining coating stability. Coupled with the release profile of Si ions from the BGN, cell proliferation and calcium deposition were enhanced in the Col-BGN samples after 28 days. Further, osteogenic differentiation was initiated as early as d 7, and each EF regime was shown to activate distinct pathways. The disrupted (4/4) regime was associated with the BMP/Smad4 pathways that up-regulate Runx2/OCN gene expression on d 7, with a lesser effect on ALP activity. In contrast, the canonical Wnt/β-Catenin signaling pathway activated through mechanotransduction cues is associated with the consecutive (12/12) regime, with significantly elevated ALP activity and Sp7 gene expression reported on d 7. In summary, our results illustrated the synergistic effects of BGN and EF in different stimulation regimes on osteogenic differentiation that can be further exploited to enhance current bone tissue engineering and regeneration approaches. STATEMENT OF SIGNIFICANCE: The unique release mechanisms of silica from bioactive glass nanoparticles (BGN) were coupled with pulsatile electric field (EF) stimulation to support hMSC osteogenic differentiation, in the absence of dexamethasone. Furthermore, the interplay with consecutive (12/12) and disrupted (4/4) stimulation regimes was investigated. The reported physical, mechanical and topographical effects of BGN and EF on the collagen coating, hMSC and the distinct progression of osteogenic differentiation (canonical Wnt/β-Catenin and BMP/Smad) triggered by respective stimulation regime were not explicitly reported previously. These results provide the fundamentals for further exploitations on BGN composites with metal ions and rotation of EF regimes to enhance osteogenic differentiation. The goal is sustaining continual osteogenic differentiation and achieving a more physiologically-relevant state and bone constructs in vitro., Competing Interests: Declaration of Competing Interest The authors have no competing financial interests to be declared., (Copyright © 2022. Published by Elsevier Ltd.)

Electrospun fibers of poly (lactic acid) (PLA) containing 10 and 20 wt% of bioactive glass (n-BG) and magnesium oxide (n-MgO) nanoparticles of ca. 27 and 23 nm respectively, were prepared toward to application in bone tissue engineering. The addition of both nanoparticles into the PLA will produce a synergic effect increasing its bioactivity and antimicrobial behavior. Neat PLA scaffold and the composites with MgO showed an average fiber diameter of 1.7 ± 0.6 μm, PLA/n-BG and PLA/n-BG/n-MgO fibers presented a significant diameter increase reaching values of ca. 3.1 ± 0.8 μm. Young's modulus of the electrospun scaffolds was affected by the direct presence of the particle and scaffold morphologies. All the composites having n-BG presented bioactivity through the precipitation of hydroxyapatite structures on the surface. Although n-MgO did not add bioactivity to the PLA fibers, they were able to render antimicrobial characteristics reducing the S. aureus viability around 30%, although an effect on E. coli strain was not observed. PLA/n-BG nanocomposites did not display any significant antimicrobial behavior. The different composites increased the alkaline phosphatase (ALP) expression as compared with pure PLA barely affecting the cell viability, meaning a good osteoblastic phenotype expression capacity, with PLA/n-BG presenting the highest osteoblastic expression., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Multidrug-resistant bacterial strains represent an emerging global health threat and a great obstacle for bone tissue engineering. One of the major components of the extracellular matrix of the bone is a collagen protein, while selenium is an element that has antimicrobial potential, and is also important for bone metabolism and bone health. Here we represent the incorporation of selenium nanoparticles (SeNPs) synthesized by the green chemical reduction method into collagen gels to produce a composite material, collagen/SeNPs, with antimicrobial properties. The samples were comprehensively characterized by zeta potential measurements, dynamic light scattering inductively coupled plasma-mass spectrometry (ICP-MS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), optical microscopy, field-emission scanning electron microscopy (FE-SEM), and differential scanning calorimetry The cytotoxicity of the SeNPS, as well as collagen/SeNPs, was tested on the MRC-5 cells. It was revealed that collagen/SeNPS expressed a lower cytotoxic effect. Collagen/SeNPs showed significant antibacterial activity against all tested Gram-positive strains, the major causative agents of orthopedic infections as well as Candida albicans . Furthermore, three-dimensional β-tricalcium phosphate (3D-TCP) scaffolds were fabricated by a well-established 3D printing (lithography) method, and afterward preliminary coated by newly-synthesized SeNPs or collagen/SeNPs. In addition, uncoated 3D-TCP scaffolds as well as coated by collagen/SeNPs were subjected to biofilm formation. The production of Staphylococcus aureus biofilm on coated scaffolds by collagen/SeNPs was significantly reduced compared to the uncoated ones.

Bioprinting has seen significant progress in recent years for the fabrication of bionic tissues with high complexity. However, it remains challenging to develop cell-laden bioinks exhibiting superior physiochemical properties and bio-functionality. In this study, a multifunctional nanocomposite bioink is developed based on amine-functionalized copper (Cu)-doped mesoporous bioactive glass nanoparticles (ACuMBGNs) and a hydrogel formulation relying on dynamic covalent chemistry composed of alginate dialdehyde (oxidized alginate) and gelatin, with favorable rheological properties, improved shape fidelity, and structural stability for extrusion-based bioprinting. The reversible dynamic microenvironment in combination with the impact of cell-adhesive ligands introduced by aminated particles enables the rapid spreading (within 3 days) and high survival (>90%) of embedded human osteosarcoma cells and immortalized mouse bone marrow-derived stroma cells. Osteogenic differentiation of primary mouse bone marrow stromal stem cells (BMSCs) and angiogenesis are promoted in the bioprinted alginate dialdehyde-gelatin (ADA-GEL or AG)-ACuMBGN scaffolds without additional growth factors in vitro, which is likely due to ion stimulation from the incorporated nanoparticles and possibly due to cell mechanosensing in the dynamic matrix. In conclusion, it is envisioned that these nanocomposite bioinks can serve as promising platforms for bioprinting complex 3D matrix environments providing superior physiochemical and biological performance for bone tissue engineering., (© 2022 Wiley-VCH GmbH.)

3D printing enables a better control over the microstructure of bone restoring constructs, addresses the challenges seen in the preparation of patient-specific bone scaffolds, and overcomes the bottlenecks that can appear in delivering drugs/growth factors promoting bone regeneration. Here, 3D printing is employed for the fabrication of an osteogenic construct made of hydrogel nanocomposites. Alginate dialdehyde-gelatin (ADA-GEL) hydrogel is reinforced by the incorporation of bioactive glass nanoparticles, i.e. mesoporous silica-calcia nanoparticles (MSNs), in two types of drug (icariin) loading. The composites hydrogel is printed as superhydrated composite constructs in a grid structure. The MSNs not only improve the mechanical stiffness of the constructs but also induce formation of an apatite layer when the construct is immersed in simulated body fluid (SBF), thereby promoting cell adhesion and proliferation. The nanocomposite constructs can hold and deliver icariin efficiently, regardless of its incorporation mode, either as loaded into the MSNs or freely distributed within the hydrogel. Biocompatibility tests showed that the hydrogel nanocomposites assure enhanced osteoblast proliferation, adhesion, and differentiation. Such optimum biological properties stem from the superior biocompatibility of ADA-GEL, the bioactivity of the MSNs, and the supportive effect of icariin in relation to cell proliferation and differentiation. Taken together, given the achieved structural and biological properties and effective drug delivery capability, the hydrogel nanocomposites show promising potential for bone tissue engineering., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The present study analyzes the capacity of collagen (coll)/sulfated glycosaminoglycan (sGAG)-based surface coatings containing bioactive glass nanoparticles (BGN) in promoting the osteogenic differentiation of human mesenchymal stroma cells (hMSC). Physicochemical characteristics of these coatings and their effects on proliferation and osteogenic differentiation of hMSC were investigated. BGN were stably incorporated into the artificial extracellular matrices (aECM). Oscillatory rheology showed predominantly elastic, gel-like properties of the coatings. The complex viscosity increased depending on the GAG component and was further elevated by adding BGN. BGN-containing aECM showed a release of silicon ions as well as an uptake of calcium ions. hMSC were able to proliferate on coll and coll/sGAG coatings, while cellular growth was delayed on aECM containing BGN. However, a stimulating effect of BGN on ALP activity and calcium deposition was shown. Furthermore, a synergistic effect of sGAG and BGN was found for some donors. Our findings demonstrated the promising potential of aECM and BGN combinations in promoting bone regeneration. Still, future work is required to further optimize the BGN/aECM combination for increasing its combined osteogenic effect.

Mesoporous bioactive glass nanoparticles (MBGNs) have demonstrated promising properties for the local delivery of therapeutically active ions with the aim to improve their osteogenic properties. Manganese (Mn), zinc (Zn), and copper (Cu) ions have already shown promising pro-osteogenic properties. Therefore, the concentration-dependent impact of MBGNs (composition in mol%: 70 SiO 2 , 30 CaO) and MBGNs containing 5 mol% of either Mn, Zn, or Cu (composition in mol%: 70 SiO 2 , 25 CaO, 5 MnO/ZnO/CuO) on the viability and osteogenic differentiation of human marrow-derived mesenchymal stromal cells (BMSCs) was assessed in this study. Mn-doped MBGNs (5Mn-MBGNs) showed a small "therapeutic window" with a dose-dependent negative impact on cell viability but increasing pro-osteogenic features alongside increasing Mn concentrations. Due to a constant release of Zn, 5Zn-MBGNs showed good cytocompatibility and upregulated the expression of genes encoding for relevant members of the osseous extracellular matrix during the later stages of cultivation. In contrast to all other groups, BMSC viability increased with increasing concentration of Cu-doped MBGNs (5Cu-MBGNs). Furthermore, 5Cu-MBGNs induced an increase in alkaline phosphatase activity. In conclusion, doping with Mn, Zn, or Cu can enhance the biological properties of MBGNs in different ways for their potential use in bone regeneration approaches., (© 2020 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Bioactive glasses (BGs) are being increasingly considered for biomedical applications. One convenient approach to utilize BGs in tissue engineering and drug delivery involves their combination with organic biomaterials in order to form composites with enhanced biocompatibility and biodegradability. In this work, mesoporous bioactive glass nanoparticles (MBGN) have been merged with polyhydroxyalkanoate microspheres with the purpose to develop drug carriers. The composite carriers (microspheres) were loaded with curcumin as a model drug. The toxicity and delivery rate of composite microspheres were tested in vitro, reaching a curcumin loading efficiency of over 90% and an improving of biocompatibility of different concentrations of MBGN due to its administrations through the composite. The composite microspheres were tested in terms of controlled release, biocompatibility and bioactivity. Our results demonstrate that the composite microspheres can be potentially used in biomedicine due to their dual effects: bioactivity (due to the presence of MBGN) and curcumin release capability.

In recent years, mesoporous bioactive glass nanoparticles (MBGNPs) have generated great attention in biomedical applications. In this study, cerium and gallium doped MBGNPs were prepared by microemulsion assisted sol-gel method in the binary SiO 2 -CaO system. MBGNPs with spheroidal and pineal shaped morphology were obtained. Nitrogen sorption analysis elucidated the mesoporous structure of synthesized nanoparticles with high specific surface area. X-ray diffraction analysis confirmed the amorphous nature of the nanoparticles. The chemical compositions of all samples were determined by inductively coupled plasma-optical emission spectrometry (ICP-OES), which revealed that the contents of cerium and gallium could be tailored by adjusting the concentrations of the precursors used for the synthesis. All MBGNPs exhibited in vitro bioactivity when immersed in simulated body fluid, except the particles doped with higher amounts than 1 mol% of cerium. MBGNPs showed antibacterial activity against S. aureus and E. coli without exhibiting cytotoxicity towards MG-63 osteoblast-like cells. Mentioned features of the obtained Ce and Ga-doped MBGNPs make them useful for multifunctional applications such as drug delivery carriers or bioactive fillers for bone tissue engineering applications., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Mesoporous silica-based nanoparticles (MSNs) are considered promising drug carriers because of their ordered pore structure, which permits high drug loading and release capacity. The dissolution of Si and Ca from MSNs can trigger osteogenic differentiation of stem cells towards extracellular matrix calcification, while Mg and Sr constitute key elements of bone biology and metabolism. The aim of this study was the synthesis and characterization of sol-gel-derived MSNs co-doped with Ca, Mg and Sr. Their physico-chemical properties were investigated by X-ray diffraction (XRD), scanning electron microscopy with energy dispersive X-ray analysis (SEM/EDX), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence spectroscopy (XRF), Brunauer Emmett Teller and Brunauer Joyner Halenda (BET/BJH), dynamic light scattering (DLS) and ζ-potential measurements. Moxifloxacin loading and release profiles were assessed with high performance liquid chromatography (HPLC) cell viability on human periodontal ligament fibroblasts and their hemolytic activity in contact with human red blood cells (RBCs) at various concentrations were also investigated. Doped MSNs generally retained their textural characteristics, while different compositions affected particle size, hemolytic activity and moxifloxacin loading/release profiles. All co-doped MSNs revealed the formation of hydroxycarbonate apatite on their surface after immersion in simulated body fluid (SBF) and promoted mitochondrial activity and cell proliferation.

Bioactive glasses (BG) are versatile materials for various biomedical applications, including bone regeneration and wound healing, due to their bone bonding, antibacterial, osteogenic, and angiogenic properties. In this study, we aimed to enhance the antibacterial activity of SiO 2 -CaO mesoporous bioactive glass nanoparticles (MBGN) by incorporating silver (Ag) through a surface modification approach. The modified Ag-containing nanoparticles (Ag-MBGN) maintained spherical shape, mesoporous structure, high dispersity, and apatite-forming ability after the surface functionalization. The antibacterial activity of Ag-MBGN was assessed firstly using a planktonic bacteria model. Moreover, a 3D tissue-engineered infected skin model was used for the first time to evaluate the antibacterial activity of Ag-MBGN at the usage dose of 1 mg/mL. In the planktonic bacteria model, Ag-MBGN exhibited a significant antibacterial effect against both Pseudomonas aeruginosa and Staphylococcus aureus in comparison to non-engineered (Ag-free) MBGN and the blank control. Moreover, Ag-MBGN did not show cytotoxicity towards fibroblasts at the usage dose. However, in the 3D infected skin model, Ag-MBGN only demonstrated antibacterial activity against S. aureus whereas their antibacterial action against P. aeruginosa was inhibited. In conclusion, surface modification by Ag incorporation is a feasible approach to enhance the antibacterial activity of MBGN without significantly impacting their morphology, polydispersity, and apatite-forming ability. The prepared Ag-MBGN are attractive building blocks for the development of 3D antibacterial scaffolds for tissue engineering., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Copper-containing bioactive glass nanoparticles (Cu-BG NPs) with designed compositions and sizes were synthesized and incorporated into chitosan (CH)/silk fibroin (SF)/glycerophosphate (GP) composites to prepare injectable hydrogels for cell-free bone repair. The resulting Cu-BG/CH/SF/GP gels were found to exhibit well-defined injectability and to undergo rapid gelation at physiological temperature and pH. They were highly porous and showed the ability to administer Si, Ca and Cu ions at their respective safe doses in a sustained and controlled manner. In vitro studies revealed that the gels supported the growth of seeded MC3T3-E1 and human umbilical vein endothelial cells, and effectively induced them toward osteogenesis and angiogenesis, respectively. In vivo bone repair based on a critical-size rat calvarial bone defect model demonstrated that the optimal Cu-BG/CH/SF/GP gel was able to fully restore the bone defect with formation of vascularized bone tissue and mineralized collagen deposition during a treatment period of 8 weeks without utilization of any cells and/or growth factors. The results suggest that the presently developed Cu-BG/CH/SF/GP composite hydrogels have great potential and translation ability for bone regeneration owing to their thermo-sensitive properties, cell-free bioactivity, and cost-effectiveness. STATEMENT OF SIGNIFICANCE: Hydrogels loaded with cells and/or growth factors exhibit potential in bone repair. However, they have been facing obstacles related to the clinic translation. Here, a novel type of hydrogel system consisting of copper-containing bioactive glass nanoparticles and chitosan/silk fibroin composite was developed. These gels showed injectability and thermally triggered in situ gelation properties and were able to administer the release of ions at safe but effective doses in a controlled manner while inducing the seeded cells toward osteogenesis and angiogenesis. The optimal gel showed the ability to fully repair critical-size rat calvarial bone defects without involving time consuming cell processing and/or the use of expensive growth factors, confirming that this novel hydrogel system has great potential for translation to the clinic., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Mesoporous bioactive glass (BG) nanoparticles based in the system: SiO 2 -P 2 O 5 -CaO-MnO were synthesized via a modified Stöber process at various concentrations of Mn (0-7 mol %). The synthesized manganese-doped BG nanoparticles were characterized in terms of morphology, composition, in vitro bioactivity and antibacterial activity. Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Brunauer-Emmett-Teller (BET) analysis confirmed that the particles had spherical morphology (mean particle size: 110 nm) with disordered mesoporous structure. Energy dispersive X-ray spectroscopy (EDX) confirmed the presence of Mn, Ca, Si and P in the synthesized Mn-doped BG particles. Moreover, X-ray diffraction (XRD) analysis showed that Mn has been incorporated in the amorphous silica network (bioactive glass). Moreover, it was found that manganese-doped BG particles form apatite crystals upon immersion in simulated body fluid (SBF). Inductively coupled plasma atomic emission spectroscopy (ICP-OES) measurements confirmed that Mn is released in a sustained manner, which provided antibacterial effect against Bacillus subtilis, Pseudomonas aeruginosa and Staphylococcus aureus. The results indicate that the incorporation of Mn in the bioactive glass network is an effective strategy to develop novel multifunctional BG nanoparticles for bone tissue engineering.

Background: Rising criticism of currently available contrast agents for magnetic resonance imaging, either due to their side effects or limited possibilities in terms of functional imaging, evoked the need for safer and more versatile agents. We previously demonstrated the suitability of novel dextran-coated superparamagnetic iron oxide nanoparticles (SPION Dex ) for biomedical applications in terms of safety and biocompatibility., Methods: In the present study, we investigated the size-dependent cross-linking process of these particles as well as the size dependency of their imaging properties. For the latter purpose, we adopted a simple and easy-to-perform experiment to estimate the relaxivity of the particles. Furthermore, we performed an extensive analysis of the particles' storage stability under different temperature conditions, showing their superb stability and the lack of any signs of agglomeration or sedimentation during a 12 week period., Results: Independent of their size, SPION Dex displayed no irritation potential in a chick chorioallantoic membrane assay. Cell uptake studies of ultra-small (30 nm) SPION Dex confirmed their internalization by macrophages, but not by non-phagocytic cells. Additionally, complement activation-related pseudoallergy (CARPA) experiments in pigs treated with ultra-small SPION Dex indicated the absence of hypersensitivity reactions., Conclusion: These results emphasize the exceptional safety of SPION Dex , setting them apart from the existing SPION-based contrast agents and making them a very promising candidate for further clinical development., Competing Interests: Disclosure László Dézsi and János Szebeni are employed by SeroScience Ltd., Budapest, Hungary. The authors report no other conflicts of interest in this work.

Silicate-based bioactive glass nanoparticles (BGN) are gaining increasing attention in various biomedical applications due to their unique properties. Controlled synthesis of BGN is critical to their effective use in biomedical applications since BGN characteristics, such as morphology and composition, determining the properties of BGN, are highly related to the synthesis process. In the last decade, numerous investigations focusing on BGN synthesis have been reported. BGN can mainly be produced through the conventional melt-quench approach or by sol-gel methods. The latter approaches are drawing widespread attention, considering the convenience and versatility they offer to tune the properties of BGN. In this paper, we review the strategies of sol-gel processing of BGN, including those adopting different catalysts for initiating the hydrolysis and condensation of silicate precursors as well as those combining sol-gel chemistry with other techniques. The processes and mechanism of different synthesis approaches are introduced and discussed in detail. Considering the importance of the BGN morphology and composition to their biomedical applications, strategies put forward to control the size, shape, pore structure and composition of BGN are discussed. BGN are particularly interesting biomaterials for bone-related applications, however, they also have potential for other biomedical applications, e.g. in soft tissue regeneration/repair. Therefore, in the last part of this review, recently reported applications of BGN in soft tissue repair and wound healing are presented., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Copper (Cu)-containing bioactive glasses (BGs) are attracting attention for bone regeneration and wound healing since they have bone-bonding capability and potential osteogenesis and angiogenesis properties. In this study, highly dispersed and spherical Cu-containing bioactive glass nanoparticles (Cu-BGNs) were successfully synthesized via a modified Stöber method. The content of incorporated Cu in the particles could be tailored by adjusting the amount of the added Cu precursor, a procedure that had no significant effects on the morphological and structural characteristics of the nanoparticles. Cu-BGNs exhibited satisfactory apatite-forming ability, as a large quantity of apatite could form on Cu-BGNs pellets after immersion in simulated body fluid for just 3days. The incorporation of Cu exhibited positive effects on the apatite formation. In addition, both Si and Cu ions were released from the Cu-BGN in a sustained manner for at least 14days in cell culture medium, indicating the potential of the BGN as promising carriers for delivering therapeutic Cu ions. Moreover, Cu-BGNs showed no significant cytotoxicity towards human mesenchymal stem cells and fibroblast cells at concentrations of 100, 10 and 1μg/mL. Taken together, the results suggest that Cu-BGNs are promising nanoparticulate fillers to develop nanocomposites for biomedical applications especially in bone regeneration and wound healing., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Alginate dialdehyde-gelatin (ADA-GEL) constructs incorporating bioactive glass nanoparticles (BGNPs) were produced by biofabrication to obtain a grid-like highly-hydrated composite. The material could induce the deposition of an apatite layer upon immersion in a biological-like environment to sustain cell attachment and proliferation. Composites were formulated with different concentrations of BGNPs synthetized from a sol-gel route, namely 0.1% and 0.5% (w/v). Strontium doped BGNPs were also used. EDS analysis suggested that the BGNPs loading promoted the growth of bone-like apatite layer on the surface when the constructs were immersed in a simulated body fluid. Moreover, the composite constructs could incorporate with high efficiency ibuprofen as a drug model. Furthermore, the biofabrication process allowed the successful incorporation of MG-63 cells into the composite material. Cells were distributed homogeneously within the hydrogel composite, and no differences were found in cell viability between ADA-GEL and the composite constructs, proving that the addition of BGNPs did not influence cell fate. Overall, the composite material showed potential for future applications in bone tissue engineering.

In this study, highly monodispersed spherical bioactive glass nanoparticles (BGS) with a particle size of 408  ±  36 nm were synthesized using a modified Stöber method. The BGS was then functionalized with lysozyme (LY) via a simple electrostatic interaction routine under selected conditions. The LY-functionalized BGS (LY-BGS) exhibited monodispersity, spherical morphology and homogeneity in size. The incorporated content of LY could be tailored conveniently by adjusting the initial concentration of the LY precursor for functionalization. Hydroxyapatite (HA) formed on the LY-BGS after soaking in simulated body fluid (SBF) for 7 d, but the formation was retarded compared to the non-functionalized BGS. The LY-BGS showed antibacterial activity towards Gram-positive B. subtilis and  >90% of the bacteria was killed within 24 h after culture with the LY-BGS at a concentration of 1 mg ml(-1). The LY-BGS also showed cytotoxicity towards the human hepatocellular carcinoma (HepG2) cell line. In addition, the relative cytotoxicity increased with an increase in the concentration of the LY-BGS in contact with the cells. As a comparison, the LY-BGS exhibited reduced or no cytotoxicity towards human umbilical vein endothelial cells (HUVECs) at the same concentration with respect to the HepG2 groups. Notably, the relative cell viability of HepG2 was 45.9% after exposure to the LY-BGS at a concentration of 10 μg ml(-1) for 24 h, while no decrease in relative viability for the HUVECs was observed under the same conditions. This cytotoxicity window between cancerous cells and healthy cells could be expected for cancer treatment. Furthermore, the antibacterial properties and the bioactivity of LY-BGS make it a promising material for biomedical applications, particularly in the treatment of bone defects caused by tumors.

Surface functionalization of orthopedic implants is being intensively investigated to strengthen bone-to-implant contact and accelerate bone healing process. A hybrid coating, consisting of 45S5 bioactive glass (BG) individually wrapped and interconnected with fibrous cellulose nanocrystals (CNCs), is deposited on 316L stainless steel from aqueous suspension by a one-step electrophoretic deposition (EPD) process. Apart from the codeposition mechanism elucidated by means of zeta-potential and scanning electron microscopy measurements, in vitro characterization of the deposited CNCs-BG coating in simulated body fluid reveals an extremely rapid mineralization of BG particles on the coating (e.g., the formation of hydroxyapatite crystals layer after 0.5 day). A series of comparative trials and characterization methods were carried out to comprehensively understand the mineralization process of BG interacting with CNCs. Furthermore, key factors for satisfying the applicability of an implant coating such as coating composition, surface topography, and adhesion strength were quantitatively investigated as a function of mineralization time. Cell culture studies (using MC3T3-E1) indicate that the presence of CNCs-BG coating substantially accelerated cell attachment, spreading, proliferation, differentiation, and mineralization of extracellular matrix. This study has confirmed the capability of CNCs to enhance and regulate the bioactivity of BG particles, leading to mineralized CNCs-BG hybrids for improved bone implant coatings.

The bond between methacrylic polymer adhesives and dental restoratives is not perfect and may fail either in the short or in the long term. This study aims to evaluate the effects of particle incorporation in a self-etch model adhesive on mechanical and physical properties that are relevant during application and service. Filled adhesives containing 5, 10, 15 or 25wt% glass fillers were compared to their unfilled counterpart in terms of water sorption and solubility; viscosity and dynamic viscosity during polymerization were recorded using rheological measurements and compared to FTIR analysis of the real-time degree of cure. Elastic modulus and ultimate tensile strength measurements were performed in uniaxial tension; the energy to fracture was used to calculate the fracture toughness of the adhesives. Finally, the experimental adhesives were applied on dentin substrate to test the bond strength using the microtensile test. Results showed that the incorporation of 5-10wt% nanofiller to self-etching dental adhesives is efficient in accelerating the polymerization reaction and increasing the degree of cure without compromising the film viscosity for good wettability or water sorption and solubility. Fillers increased the elastic modulus, tensile strength and fracture toughness to a plateau between 5 and 15wt% filler concentration, and despite the tendency to form agglomerations, active crack pinning/deflection toughening mechanisms have been observed. The bond strength between resin composite and dentin was also improved when adhesives with up to 10wt% fillers were used, with no additional improvements with further packing. The use of fillers to reinforce dental adhesives may therefore be of great practical benefit by improving curing and mechanical properties., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

This study presents the electrophoretic deposition (EPD) of cellulose nanocrystals (CNs) and CNs-based alginate composite coatings for biomedical applications. The mechanism of anodic deposition of CNs and co-deposition of CNs/alginate composites was analyzed based on the results of zeta-potential, Fourier transform infrared spectroscopy and scanning electron microscopy (SEM) analyses. The capability of the EPD technique for manipulating the orientation of CNs and for the preparation of multilayer CNs coatings was demonstrated. The nanotopographic surface roughness and hydrophilicity of the deposited coatings were measured and discussed. Electrochemical testing demonstrated that a significant degree of corrosion protection of stainless steel could be achieved when CNs-containing coatings were present. Additionally, the one-step EPD-based processing of free-standing CNs/alginate membranes was demonstrated confirming the versatility of EPD to fabricate free-standing membrane structures compared to a layer-by-layer deposition technique. CNs and CNs/alginate nanocomposite coatings produced by EPD are potential candidates for biomedical, cell technology and drug delivery applications., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A new family of biodegradable polymer/bioactive glass (BG) composite materials has emerged based on the availability of nano-sized bioactive particles. Such novel biocomposites can have enhanced performance, in terms of mechanical properties and bioactivity, and they can be designed to be used in bone regeneration approaches. In this work, membranes of chitosan (CTS) and chitosan with bioactive glass (BG) both micron and nano sized particles (CTS/μBG, CTS/nBG, respectively) were prepared by solvent casting. Microstructural and mechanical properties were evaluated in order to compare the effects of the incorporation of micro (μBG) and nano (nBG) particles in the chitosan matrix. In vitro bioactivity tests were performed to characterize the apatite layer that is formed on the surface of the material after being immersed in simulated body fluid (SBF). The biomineralization process on the biomaterials was also followed using non-conventional dynamic mechanical analysis (DMA), both online and offline. In such DMA experiments, the change in the storage modulus, E', and the loss factor, tan δ, were measured as a function of the immersion time in SBF. The results demonstrated that CTS/nBG membranes possess enhanced mechanical properties and higher bioactivity in comparison with the CTS/μBG membranes. Such results suggest the potential of nBG for the development of bioactive composites for bone regeneration applications., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

This work investigated the effect of adding nanoparticulate (29 nm) bioactive glass particles on the bioactivity, degradation and in vitro cytocompatibility of poly(3-hydroxybutyrate) (P(3HB)) composites/nano-sized bioactive glass (n-BG). Two different concentrations (10 and 20 wt %) of nanoscale bioactive glass particles of 45S5 Bioglass composition were used to prepare composite films. Several techniques (Raman spectroscopy, scanning electron microscopy, atomic force microscopy, energy dispersive X-ray) were used to monitor their surface and bioreactivity over a 45-day period of immersion in simulated body fluid (SBF). All results suggested the P(3HB)/n-BG composites to be highly bioactive, confirmed by the formation of hydroxyapatite on material surfaces upon immersion in SBF. The weight loss and water uptake were found to increase on increasing bioactive glass content. Cytocompatibility study (cell proliferation, cell attachment, alkaline phosphatase activity and osteocalcin production) using human MG-63 osteoblast-like cells in osteogenic and non-osteogenic medium showed that the composite substrates are suitable for cell attachment, proliferation and differentiation.

In recent years, composite biomaterials have attracted attention for drug delivery applications due to the possibility of combining desired properties of their components. However, some functional characteristics, such as their drug release efficiency and likely side effects, are still unexplored. In this regard, controlled tuning of the drug release kinetic via the precise design of a composite particle system is still of high importance for many biomedical applications. This objective can be properly fulfilled through the combination of different biomaterials with unequal release rates, such as mesoporous bioactive glass nanoparticles (MBGN) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) microspheres. In this work, MBGNs and PHBV-MBGN microspheres, both loaded with Astaxanthin (ASX), were synthesised and compared in terms of ASX release kinetic, ASX entrapment efficiency, and cell viability. Moreover, the correlation of the release kinetic to phytotherapeutic efficiency and side effects was established. Interestingly, there were significant differences between the ASX release kinetic of the developed systems, and cell viability differed accordingly after 72 h. Both particle carriers effectively delivered ASX, though the composite microspheres exhibited a more prolonged release profile with sustained cytocompatibility. The release behaviour could be fine-tuned by adjusting the MBGN content in the composite particles. Comparatively, the composite particles induced a different release effect, implying their potential for sustained drug delivery applications. [ABSTRACT FROM AUTHOR]

Composite fibrous membranes based on poly(ɛ‐caprolactone) (PCL) and mesoporous bioactive glass nanoparticles (MBGNs) were fabricated by electrospinning. MBGNs and Zn‐doped MBGNs prepared by microemulsion sol–gel method were successfully incorporated inside the polymeric fibers of 240 and 385 nm in diameter for undoped and Zn‐doped PCL_MBGNs fibers, respectively. Thermal analysis showed that the concentration of MBGNs reached a maximum of around 21 wt% for Zn‐doped MBGNs. Both PCL_MBGNs and PCL_MBGNs_Zn composite membrane exhibited bioactivity after immersion in simulated body fluid (SBF). X‐ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) showed the evolution of composite membranes, confirming the formation of hydroxyapatite (HAp). However, the degradation products of membranes did not affect the viability and proliferation of murine stromal cells (ST‐2) and thus the new fiber structures represent a suitable environment for cell adhesion. Therefore, the incorporation of mesoporous glass nanoparticles doped with therapeutically active Zn2+ ions inside the PCL fibers offers the possibility to create a multifunctional biomaterial suitable for drug delivery and tissue engineering. [ABSTRACT FROM AUTHOR]

The concept of adding inorganic fillers into hydrogels to form hydrogel nanocomposites often provides advantageous properties which can be exploited for successful 3D biofabrication. In this study, a new composite hydrogel combining oxidized alginate–gelatin (ADA‐GEL) hydrogel and Laponite® nanoclay as inorganic nanofiller was successfully developed and characterized. The results showed that the addition of 0.5% (wt/vol) Laponite® nanoplatelets improved the printability of ADA‐GEL hydrogels enabling the fabrication of detailed structures since a low effect of material spreading and reduced tendency to pore closure appeared. Furthermore, a comparison of different needle types (cylindrical and conical; same inner diameter of 250 μm) in filament fusion test showed that the pattern dispensed by cylindrical tip has enhanced printing accuracy and pattern fidelity when compared with the pattern from conical tip. A glass flip test determined a processing window of 1–2 h after composite ink preparation. Overall, Laponite® /ADA‐GEL hydrogel composites are confirmed as promising inks for 3D bioprinting. [ABSTRACT FROM AUTHOR]

Nanocomposite coatings were successfully prepared by electrophoretic deposition of poly(etheretherketone) (PEEK)/graphene oxide (GO) suspensions. The GO flakes developed a large-scale co-continuous morphology with the basal plane mainly aligned with the coating surface. However, the PEEK particles were also found to be wrapped by GO nanosheets when deposited on the stainless steel substrate. Both phenomena, the co-continuous morphology and the wrapping effect, were dependent on the initial GO content in the suspension and influenced the final morphological characteristics of the thermally treated coatings. The PEEK matrix developed a dendritic morphology during its cooling from the molten state because of transcrystallinity that was induced by the incorporation of GO. The preparation of suspensions involved tip ultrasonication (TS) to deagglomerate, disperse, and mill the PEEK particles. A detailed study of the microstructure revealed that TS tended not only to reduce PEEK particle size, but also to promote an elongated shape, favourable for the nanocomposite coatings. [ABSTRACT FROM AUTHOR]

Bioactive glass is considered an ideal material for haemostasis as it releases Ca2+ ions upon hydration, which is required to support thrombosis. In this study the effects of the presence of nanoscaled bioactive glass (n- BG) in poly(3-hydroxybutyrate) (P( 3HB)) microsphere films on the structural properties, thermal properties and biocompatibility of the films were studied. The n- BG with a high surface area was also tested for its in vitro haemostatic efficacy and was found to be able to successfully reduce clot detection time. In an effort to study the effect of the roughness induced by the formation of hydroxyapatite on cellular functions such as cell adhesion, cell mobility and cell differentiation, the composite films were immersed in simulated body fluid for periods of 1, 3 and 7 days. From scanning electron microscopy images, the surface of the P( 3HB)/n- BG composite microsphere films appeared fairly uniform and smooth on day 1; however on day 3 and day 7 a rough and uneven surface was observed. The presence of hydroxyapatite on the composite microsphere films on day 3 and day 7 influenced the surface roughness of the films. However, when the P( 3HB)/n- BG composite microsphere films with enhanced surface roughness were tested for biocompatibility, reduced amounts of protein adsorption and cell adhesion were observed. This study thus revealed that there is an optimal surface roughness for the P( 3HB) microsphere films for increased cell adhesion, beyond which it could be deleterious for cell adhesion and differentiation. © 2016 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Monodispersed spherical Ag-doped bioactive glass nanoparticles (Ag-BGNs) were synthesized by a modified Stöber method combined with surface modification. The surface modification was carried out at 25, 60, and 80 °C, respectively, to investigate the influence of processing temperature on particle properties. Energy-dispersive X-ray spectroscopy (EDS) results indicated that higher temperatures facilitate the incorporation of Ag. Hydroxyapatite (HA) formation on Ag-BGNs was detected upon immersion of the particles in simulated body fluid for 7 days, which indicated that Ag-BGNs maintained high bioactivity after surface modification. The conducted antibacterial assay confirmed that Ag-BGNs had an antibacterial effect on E. coli. The above results thereby suggest that surface modification is an effective way to incorporate Ag into BGNs and that the modified BGNs can remain monodispersed as well as exhibit bioactivity and antibacterial capability for biomedical applications. [ABSTRACT FROM AUTHOR]

The importance of titania (TiO 2 ) as the main component of photocatalytic and photovoltaic devices or its employment in sensors, biomedical coatings and as anticorrosion or antioxidation agent, is highlighted by the increasing number of systems in which titania is being widely used. Many of the attractive applications of TiO 2 require the manufacture of thin (and thick) films and layered structures . In this regard, electrophoretic deposition (EPD) has gained increasing attention over the last years to process TiO 2 nanoparticles ( n -TiO 2 ) for production of a variety of TiO 2 layers, films and coatings. This review compiles the different aspects involved in the fabrication of TiO 2 coatings by EPD of n -TiO 2 , first focusing on the general aspects of the deposition process and the parameters involved, and considering further the specific requirements for given applications. The recent advances achieved are discussed and avenues for future research and innovations on the EPD of n -TiO 2 are highlighted. [ABSTRACT FROM AUTHOR]

The lymphatic system is crucial for the regeneration of many tissues due to its fundamental role in immune cell trafficking, protein transport, and tissue homeostasis maintenance. Strategies stimulating lymphangiogenesis can provide new therapeutic approaches for tissue repair and regeneration (e.g., chronic wound healing). Here, we explored the effects of cerium-containing mesoporous bioactive glass nanoparticles (Ce-MBGNs) on lymphangiogenesis. The results showed that the extracts of Ce-MBGNs (1, 5, or 10 wt/v%) were non-cytotoxic toward lymphatic endothelial cells (LECs), while they enhanced the proliferation of LECs. Moreover, as evidenced by the scratch wound healing and Transwell migration assays, conditioned media containing the extract of Ce-MBGNs (1 wt/v%) could enhance the migration of LECs in comparison to the blank control and the media containing vascular endothelial growth factor-C (VEGF-C, 50 ng/mL). Additionally, a tube-formation assay using LECs showed that the extract of Ce-MBGNs (1 wt/v%) promoted lymphatic vascular network formation. Western blot results suggested that Ce-MBGNs could induce lymphangiogenesis probably through the HIF-1α/VEGFR-3 pathway. Our study for the first time showed the effects of Ce-MBGNs on stimulating lymphangiogenesis in vitro, highlighting the potential of Ce-MBGNs for wound healing. [ABSTRACT FROM AUTHOR]

Because of the increased use of titanium dioxide (TiO2) nanoparticles (NPs) in tissue engineering (TE), and in new constructs for cardiac TE, their effect was studied on three relevant cell types: Adult rat ventricular cardiomyocytes, human embryonic stem cell-derived cardiomyocytes (hESC-CM) and fibroblasts. For adult rat myocytes, 10 μg/mL TiO2 NPs showed no significant effect on myocyte survival over 24 h or acute myocyte contractility. Increasing the concentration to 100 μg/mL was seen to reduce contraction amplitude ( p < 0.05). For hESC-CM, 10 μg/mL TiO2 reduced the beating rate significantly by 24 h. No arrhythmias or cessation of beating were observed in either cell type. Culturing fibroblasts in 5-150 μg/mL TiO2 significantly reduced cell proliferation at day 4 and increased cell death. We conclude that there may be modest but potentially adverse effects of TiO2 NPs if used in fast degrading polymers for myocardial tissue engineering (MTE) applications. [ABSTRACT FROM AUTHOR]

The article discusses a study on the production of poly(lactide- co-glycolide) (PLGA)- amorphous tricalcium phosphate (ATCP) nanocomposite components with defined shape for orthopedic surgery based on observed improved bioactivity and controlled degradation of solvent-cast films of PLGA and spherical ATCP nanoparticles. ATCP nanoparticles were prepared through flame spray synthesis. It concludes that suitably nanosized and shaped reactive inorganic fillers can be incorporated into biodegradable polymers through optimal processing conditions.

Abstract: Poly(3-hydroxybutyrate) (P(3HB)) composites with bioactive glass particles and multiwall carbon nanotubes (MWCNTs) were prepared and used to identify whether the electrical properties of MWCNTs can be used to detect the bioactivity of P(3HB)/bioactive glass composites. The presence of MWCNTs (2–7wt.%) increased the surface roughness of the composites. The presence of MWCNTs in low quantity enhanced MG-63 osteoblast-like cell attachment and proliferation compared to composites with higher concentration of MWCNTs. Current–voltage measurements demonstrated that the electrical resistance of the composites containing bioactive glass particles decreased over a 45-day immersion period in SBF, whereas composites without bioactive glass showed no significant change over the same period. [Copyright &y& Elsevier]

Carbon nanotubes (CNTs)/La0.6Sr0.4Co0.8Fe0.2O3−δ (LSCF) composite films have been fabricated by electrophoretic codeposition on Ce0.9Gd0.1O1.95 (CGO) substrates. CNTs are used as a sacrificial phase to produce ordered porous LSCF cathodes for intermediate temperature solid oxide fuel cells. The synthesis of LSCF powder by a modified sol–gel route is presented. The possible mechanism of formation of CNT/LSCF composite nanoparticles in suspension is discussed. Moreover the optimal suspension composition and the conditions for achieving successful electrophoretic deposition (EPD) of CNTs/LSCF composite nanoparticles were evaluated. Experimental results showed that the CNTs were homogeneously distributed and mixed with LSCF nanoparticles forming a mesh-like structure, which resulted in a highly porous LSCF film when the CNTs were burned out during heat treatment in air at 800°C for 2 h. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD) techniques were employed to characterize the microstructure of the precursors and of the composite films. [ABSTRACT FROM AUTHOR]

Nanotechnology has the potential to revolutionise our futures, but has also prompted concerns about the possibility that nanomaterials may harm humans or the biosphere. The unique properties of nanoparticles, that give them novel size dependent functionalities, may also have the potential to cause harm. Discrepancies in existing human health and environmental studies have shown the importance of good quality, well-characterized reference nanomaterials for toxicological studies. Here we make a case for the importance of the detailed characterization of nanoparticles, using several methods, particularly to allow the recognition of impurities and the presence of chemically identical but structurally distinct phases. Methods to characterise fully, commercially available multi-wall carbon nanotubes at different scales, are presented. [ABSTRACT FROM AUTHOR]

Abstract: Electrophoretic deposition (EPD) has been gaining increasing interest as an economical and versatile processing technique for the production of novel coatings or films of carbon nanotubes (CNTs) on conductive substrates. The purpose of the paper is to present an up-to-date comprehensive overview of current research progress in the field of EPD of CNTs. The paper specifically reviews the preparation and characterisation of stable CNT suspensions, and the mechanism of the EPD process; it includes discussion of pure CNT coatings and CNT/nanoparticle composite films. A complete discussion of the EPD parameters is presented, including electrode materials, deposition time, electrode separation, deposition voltage and resultant electric field. The paper highlights potential applications of the resulting CNT and CNT/composite structures, in areas such as field emission devices, fuel cells, and supercapacitors. [Copyright &y& Elsevier]