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The thermal stability and degradation, near-to-surface mechanical properties, and scratch resistance and damage mechanism of poly(etheretherketone) (PEEK)/reduced graphene oxide (RGO) nanocomposite coatings are analyzed and discussed in terms of their nanosheet content and microstructure. Although RGO modified the thermal stability and degradation of the polymeric matrix, for instance, by slightly reducing the onset degradation temperature, its addition was not a limiting factor in the PEEK processing. Respecting the microstructural features induced by the nanosheets, the nanocomposite coatings were found to exhibit (i) a partially exfoliated and large-scale co-continuous morphology related to RGO nanosheets whose basal planes were mainly aligned with the coating surface, (ii) a dendritic morphology of PEEK domains related to transcrystallinity, (iii) and irregular domains associated with the deposition of PEEK particles wrapped by the nanosheets. The changes provoked by RGO in the morphology and PEEK crystalline phase influenced the near-to-surface mechanical properties, scratch resistance, and scratch damage mechanism of the nanocomposite coatings. Within this context, the interlayer strength between the nanosheets in the large-scale co-continuous morphology and PEEK transcrystallinity had an important effect. Furthermore, the random-bumpy surface texture formed by the irregular PEEK domains together with the conformal cracking damage mechanism was decisive in the scratch response of the PEEK/RGO nanocomposite coatings. The comprehensive characterization carried out in this work concludes that PEEK/RGO electrophoretic coatings are suitable for a variety of applications requiring tribo-mechanical resistance.

Introduction: The sol-gel method for production of mesoporous bioactive glass nanoparticles (MBGNs) has been adapted to synthesize tricalcium silicate (TCS) particles which, when formulated with other additives, form the gold standard for dentine-pulp complex regeneration. Comparison of TCS and MBGNs obtained by sol-gel method is critical considering the results of the first ever clinical trials of sol-gel BAG as pulpotomy materials in children. Moreover, although lithium (Li) based glass ceramics have been long used as dental prostheses materials, doping of Li ion into MBGNs for targeted dental applications is yet to be investigated. The fact that lithium chloride benefits pulp regeneration in vitro also makes this a worthwhile undertaking. Therefore, this study aimed to synthesize TCS and MBGNs doped with Li by sol-gel method, and perform comparative characterizations of the obtained particles.Methods: TCS particles and MBGNs containing 0%, 5%, 10% and 20% Li were synthesized and particle morphology and chemical structure determined. Powder concentrations of 15mg/10 mL were incubated in artificial saliva (AS), Hank’s balanced saline solution (HBSS) and simulated body fluid (SBF), at 37°C for 28 days and pH evolution and apatite formation, monitored. Bactericidal effects against S. aureus and E. coli, as well as possible cytotoxicity against MG63 cells were also evaluated through turbidity measurements.Results: MBGNs were confirmed to be mesoporous spheres ranging in size from 123 nm to 194 nm, while TCS formed irregular nano-structured agglomerates whose size was generally larger and variable. From ICP-OES data, extremely low Li ion incorporation into MBGNs was detected. All particles had an alkalinizing effect on all immersion media, but TCS elevated pH the most. SBF resulted in apatite formation for all particle types as early as 3 days, but TCS appears to be the only particle to form apatite in AS at a similar period. Although all particles had an effect on both bacteria, this was pronounced for undoped MBGNs. Whereas all particles are biocompatible, MBGNs showed better antimicrobial properties while TCS particles were associated with greater bioactivity.Conclusion: Synergizing these effects in dental biomaterials may be a worthwhile undertaking and realistic data on bioactive compounds targeting dental application may be obtained by varying the immersion media.

Fragestellung: Das initial von Hench entwickelte 45S5-bioaktive Glas (BG) weist trotz seiner herausragenden bioaktiven Eigenschaften einige Limitationen auf. Daher wird nach alternativen Glaskompositionen für die Gewährleistung einer optimalen Regeneration von knöchernen Defekten gesucht. [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Fragestellung: Das 45S5-bioaktive Glas (BG; Zusammensetzung in wt%: 45 SiO2, 24,5 CaO, 24,5 Na2O, 6 P2O5) wird als synthetisches osteoproduktives Biomaterial zur Regeneration von Knochendefekten eingesetzt. Durch Freisetzung seiner Bestandteile in ionisierter Form nimmt BG Einfluss auf die umgebenden [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Electrospun fibers of shape memory triethoxysilane-terminated poly(epsilon-caprolactone) (PCL-TES) loaded with bioactive glasses (BG) are here presented. Unloaded PCL-TES, as well as PCL/BG nanocomposite fibers, are also considered for comparison. It is proposed that hydrolysis and condensation reactions take place between triethoxysilane groups of the polymer and the silanol groups at the BG particle surface, thus generating additional crosslinking points with respect to those present in the PCL-TES system. The as-spun PCL-TES/BG fibers display excellent shape memory properties, in terms of shape fixity and shape recovery ratios, without the need of a thermal crosslinking treatment. BG particles confer in vitro bioactivity to PCL-based nanocomposite fibers and favor the precipitation of hydroxycarbonate apatite on the fiber surface. Preliminary cytocompatibility tests demonstrate that the addition of BG particles to PCL-based polymer does not inhibit ST-2 cell viability. This novel approach of using bioactive glasses not only for their biological properties, but also for the enhancement of shape memory properties of PCL-based polymers, widens the versatility and suitability of the obtained composite fibers for a huge portfolio of biomedical applications., Graphical abstract Image 1, Highlights • Investigation of the shape memory behavior of a hybrid PCL-based/bioactive glass material. • Use of benign solvents for the electrospinning to obtain bioactive composite fibers with shape memory properties. • Fibers have excellent shape memory properties and show bioactivity upon immersion in simulated body fluid solution.

This study utilized extrusion-based 3D printing technology to fabricate calcium-cross-linked alginate dialdehyde-gelatin scaffolds for bone regeneration. The surface of polymeric constructs was modified with mussel-derived polydopamine (PDA) in order to induce biomineralization, increase hydrophilicity, and enhance cell interactions. Microscopic observations revealed that the PDA layer homogeneously coated the surface and did not appear to induce any distinct change in the microstructure of the scaffolds. The PDA-functionalized scaffolds were more mechanically stable (compression strength of 0.69 ± 0.02 MPa) and hydrophilic (contact angle of 26) than non-modified scaffolds. PDA-decorated ADA-GEL scaffolds demonstrated greater durability. As result of the 18-days immersion in simulated body fluid solution, the PDA-coated scaffolds showed satisfactory biomineralization. Based on theoretical energy analysis, it was shown that the scaffolds coated with PDA interact spontaneously with osteocalcin and osteomodulin (binding energy values of −35.95 kJ mol−1 and −46.39 kJ mol−1, respectively), resulting in the formation of a protein layer on the surface, suggesting applications in bone repair. PDA-coated ADA-GEL scaffolds are capable of supporting osteosarcoma MG-63 cell adhesion, viability (140.18% after 7 days), and proliferation. In addition to increased alkaline phosphatase secretion, osteoimage intensity also increased, indicating that the scaffolds could potentially induce bone regeneration. As a consequence, the present results confirm that 3D printed PDA-coated scaffolds constitute an intriguing novel approach for bone tissue engineering.

This research has addressed a complete study of the bioactivity of bioactive glass coatings obtained by atmospheric plasma spraying. The coatings have been characterized in terms of microstructure, adhesion, crystalline phases and bioactivity. Hydroxycarbonate apatite formation was also monitored following a standard protocol and the in vitro cell response was evaluated by human osteoblast-like cells (MG-63 cells) incubation. The obtained coatings shown a microstructure typical of glass coatings. A simulated body fluid test proved that coatings are capable of developing a surface layer of hydroxycarbonate apatite whereas the appearance of this phase takes place at a longer time than that observed for the powder feedstock. Cell-culture test showed multidirectional growth of MG-63 cells which promoted good contact between cells and the surface of the coating. This study has confirmed a positive effect of the coatings in terms of surface bioactivity and, more interestingly, it has proven an adequate cell-material interaction on the coating surface. Este trabajo ha abordado un estudio completo de la bioactividad de recubrimientos de vidrio bioactivo depositados mediante proyección térmica por plasma atmosférico. Se han caracterizado la microestructura, la adherencia, las fases cristalinas y la bioactividad de los recubrimientos obtenidos. También se ha estudiado la formación de hidroxiapatita carbonatada siguiendo un protocolo estándar y se ha evaluado la respuesta in vitro de los recubrimientos mediante su incubación con osteoblastos humanos (células MG-63). Los recubrimientos obtenidos han mostrado una microestructura típica de recubrimientos de vidrio. Tras la inmersión en fluido biológico simulado, se ha comprobado que el recubrimiento es capaz de desarrollar una capa superficial de hidroxiapatita carbonatada, aunque la velocidad de aparición de esta capa es menor que la observada para el polvo de vidrio de partida. El ensayo de cultivo celular ha mostrado un crecimiento multidireccional de las células MG-63, dando lugar a un buen contacto entre las células y la superficie del recubrimiento. Este estudio ha confirmado un efecto positivo de los recubrimientos en términos de bioactividad de la superficie y, lo que es más interesante, ha demostrado una adecuada interacción célula-material sobre la superficie del recubrimiento.

Bioactive glasses (BGs) have been a focus of research for over five decades for several biomedical applications. Although their use in bone substitution and bone tissue regeneration has gained important attention, recent developments have also seen the expansion of BG applications to the field of soft tissue engineering. Hard and soft tissue repair therapies can benefit from the biological activity of metallic ions released from BGs. These metallic ions are incorporated in the BG network not only for their biological therapeutic effects but also in many cases for influencing the structure and processability of the glass and to impart extra functional properties. The “classical” elements in silicate BG compositions are silicon (Si), phosphorous (P), calcium (Ca), sodium (Na), and potassium (K). In addition, other well-recognized biologically active ions have been incorporated in BGs to provide osteogenic, angiogenic, anti-inflammatory, and antibacterial effects such as zinc (Zn), magnesium (Mg), silver (Ag), strontium (Sr), gallium (Ga), fluorine (F), iron (Fe), cobalt (Co), boron (B), lithium (Li), titanium (Ti), and copper (Cu). More recently, rare earth and other elements considered less common or, some of them, even “exotic” for biomedical applications, have found room as doping elements in BGs to enhance their biological and physical properties. For example, barium (Ba), bismuth (Bi), chlorine (Cl), chromium (Cr), dysprosium (Dy), europium (Eu), gadolinium (Gd), ytterbium (Yb), thulium (Tm), germanium (Ge), gold (Au), holmium (Ho), iodine (I), lanthanum (La), manganese (Mn), molybdenum (Mo), nickel (Ni), niobium (Nb), nitrogen (N), palladium (Pd), rubidium (Rb), samarium (Sm), selenium (Se), tantalum (Ta), tellurium (Te), terbium (Tb), erbium (Er), tin (Sn), tungsten (W), vanadium (V), yttrium (Y) as well as zirconium (Zr) have been included in BGs. These ions have been found to be particularly interesting for enhancing the biological performance of doped BGs in novel compositions for tissue repair (both hard and soft tissue) and for providing, in some cases, extra functionalities to the BG, for example fluorescence, luminescence, radiation shielding, anti-inflammatory, and antibacterial properties. This review summarizes the influence of incorporating such less-common elements in BGs with focus on tissue engineering applications, usually exploiting the bioactivity of the BG in combination with other functional properties imparted by the presence of the added elements.

Supplemental Material, sj-pdf-1-jba-10.1177_08853282211073731 for Synthesis and characterization of a collagen-based composite material containing selenium nanoparticles by Magdalena M Stevanovi��, Nenad Filipovi��, Maja Kuzmanovi��, Nina Tomi��, Du��an U��jak, Marina Milenkovi��, Kai Zheng, Juergen Stampfl and Aldo R Boccaccini in Journal of Biomaterials Applications

Antimicrobial resistance (AMR) and infections caused by multidrug-resistant microbial pathogens represent one of the major clinical challenges responsible for high-level morbidity and mortality. They are a significant problem to the public health and the economic stability of societies all over the world. In November 2021 WHO has declared AMR as one of the top 10 global public health threats (Antimicrobial resistance (who.int)). According to CDC’s 2019 AMR Report, although declining since 2013, with 2.8 million new cases and more than 35,000 deaths each year, the number of people facing the AMR problem in United States is still too high (Antibiotic Resistance Threats in the United States, 2019 (cdc.gov)). AMR also remains the major health concern of EU with more than 670,000 new cases of infections caused by antibiotic-resistant bacterial strains and more than 33,000 deaths per year (Antimicrobial resistance surveillance in Europe 2022 - 2020 data (europa.eu)). In 2019 China recorded 39-% drop of antibiotic use in hospitalised patients compare to 2011 (Antimicrobial resistance - China (who.int)). Still, with 73,000 estimated new cases only for multi-drug resistant tuberculosis, the region remained at second position of the global highest incident rates (Antimicrobial resistance - China (who.int)). Each year a large number of people receive different kinds of implants, for example, hip or knee. However recent discoveries reveal that, either during the operative protocol or due to secondary infections, the implant’s surface could be colonized by bacteria, fungi, or both which can have serious consequences on a patient’s health. According to Annual Epidemiological Report of ECDC in 2016, post-surgical infections were identified as most common healthcare-associated infections (Surgical site infections - Annual Epidemiological Report 2016 [2014 data] (europa.eu)). In recent years it has been also recognized that microbial biofilms are ubiquitous, which has resulted in a number of studies from a biofilm perspective. Currently, great efforts are focused on the development of innovative therapeutic strategies regarding both novel drug candidates and drug delivery systems for treating microbial infections associated with implants. However, despite all these efforts as well as the urgent need, an effective and long-lasting solution to this problem is still not found. In the last decades, great attention is paid to nanostructured polymeric materials and nanocomposites because of their unique properties, which make them appropriate candidates for various applications in different medical and pharmaceutical fields. This Research Topic draws attention to the up-to-date findings regarding these issues and advanced therapeutic strategies and approaches as possible solutions.

In this study, binary SiO2-CaO hollow mesoporous bioactive glass nanoparticles (HMBGNs) are prepared by combing selective etching and impregnation strategies. Spherical silica particles (SiO2 NPs) are used as hard cores to assemble cetyltrimethylammonium bromide (CTAB)/silica shells, which are later removed by selective etching to generate a hollow structure. After the removal of CTAB by calcination, the mesoporous shell of particles is formed. Calcium (Ca) is incorporated into the particles using impregnation by soaking the etched SiO2 NPs in calcium nitrate aqueous solution. The amount of incorporated Ca is tailorable by controlling the ratio of SiO2 NPs:calcium nitrate in the soaking solution. The produced HMBGNs are bioactive, as indicated by the rapid formation of hydroxyapatite on their surfaces after immersion in simulated body fluid. In a direct culture with MC3T3-E1 cells, HMBGNs were shown to exhibit concentration-dependent cytotoxicity and can stimulate osteogenic differentiation of MC3T3-E1 cells at concentrations of 1, 0.5, and 0.25 mg/mL. Our results indicate that the combination of selective etching and impregnation is a feasible approach to produce hierarchical HMBGNs. The produced hollow particles have potential in drug delivery and bone tissue regeneration applications, and should be further investigated in detailed in vitro and in vivo studies. European Union’s Horizon 2020 research and innovation program 685872-MOZART

Ti6Al4V as a common implant material features good mechanical properties and corrosion resistance. However, untreated, it lacks bioactivity. In contrast, coatings with calcium phosphates (CaP) were shown to improve cell–material interactions in bone tissue engineering. Therefore, this work aimed to investigate how to tailor biomimetic CaP coatings on Ti6Al4V substrates using modified biomimetic calcium phosphate (BCP) coating solutions. Furthermore, the impact of substrate immersion in a 1 M alkaline CaCl2 solution (pH = 10) on subsequent CaP coating formation was examined. CaP coatings were characterized via scanning electron microscopy, x-ray diffraction, energy-dispersive x-ray spectroscopy, and laser-scanning microscope. Biocompatibility of coatings was carried out with primary human osteoblasts analyzing cell morphology, proliferation, collagen type 1, and interleukin 6 and 8 release. Results indicate a successful formation of low crystalline hydroxyapatite (HA) on top of every sample after immersion in each BCP coating solution after 14 days. Furthermore, HA coating promoted cell proliferation and reduced the concentration of interleukins compared to the uncoated surface, assuming increased biocompatibility.

This paper seeks to examine how the Mn-Co spinel interconnect coating microstructure can in-fluence the Cr contamination in an oxygen electrode of intermediate temperature Solid Oxide Cells at the operating temperature of 750 °C. A Mn-Co spinel coating is processed on Crofer 22 APU substrates by electrophoretic deposition and subsequently sintered following both the one-step and two-step sintering, in order to obtain significantly different densification levels. The electrochemical characterization is performed on anode supported cells with a LSCF cathode. The cells were aged prior to the electrochemical characterization in contact with the spinel coated Crofer 22 APU at 750 °C for 250 hours. Current-voltage and impedance spectra of the cells were measured after the exposure with the interconnect. Post-mortem analysis of the interconnect and the cell was carried out in order to assess the Cr retention capability of coatings with different microstructures.

Biodegradable hydrogels that promote stem cell differentiation into neurons in three dimensions (3D) are highly desired in biomedical research to study drug neurotoxicity or to yield cell-containing biomaterials for neuronal tissue repair. Here, we demonstrate that oxidized alginate-gelatin-laminin (ADA-GEL-LAM) hydrogels facilitate neuronal differentiation and growth of embedded human induced pluripotent stem cell (hiPSC) derived neurospheres. ADA-GEL and ADA-GEL-LAM hydrogels exhibiting a stiffness close to ~5 kPa at initial cell culture conditions of 37 °C were prepared. Laminin supplemented ADA-GEL promoted an increase in neuronal differentiation in comparison to pristine ADA-GEL, with enhanced neuron migration from the neurospheres to the bulk 3D hydrogel matrix. The presence of laminin in ADA-GEL led to a more than two-fold increase in the number of neurospheres with migrated neurons. Our findings suggest that laminin addition to oxidized alginate-gelatin hydrogel matrices plays a crucial role to tailor oxidized alginate-gelatin hydrogels suitable for 3D neuronal cell culture applications.

A hydrogel system based on oxidized alginate covalently crosslinked with gelatin (ADA-GEL) has been utilized for different biofabrication approaches to design constructs, in which cell growth, proliferation and migration have been observed. However, cell–bioink interactions are not completely understood and the potential effects of free aldehyde groups on the living cells have not been investigated. In this study, alginate, ADA and ADA-GEL were characterized via FTIR and NMR, and their effect on cell viability was investigated. In the tested cell lines, there was a concentration-dependent effect of oxidation degree on cell viability, with the strongest cytotoxicity observed after 72 h of culture. Subsequently, primary human cells, namely fibroblasts and endothelial cells (ECs) were grown in ADA and ADA-GEL hydrogels to investigate the molecular effects of oxidized material. In ADA, an extremely strong ROS generation resulting in a rapid depletion of cellular thiols was observed in ECs, leading to rapid necrotic cell death. In contrast, less pronounced cytotoxic effects of ADA were noted on human fibroblasts. Human fibroblasts had higher cellular thiol content than primary ECs and entered apoptosis under strong oxidative stress. The presence of gelatin in the hydrogel improved the primary cell survival, likely by reducing the oxidative stress via binding to the CHO groups. Consequently, ADA-GEL was better tolerated than ADA alone. Fibroblasts were able to survive the oxidative stress in ADA-GEL and re-entered the proliferative phase. To the best of our knowledge, this is the first report that shows in detail the relationship between oxidative stress-induced intracellular processes and alginate di-aldehyde-based bioinks.

Infectious diseases are a significant burden on the public health and the economic stability of societies all over the world. Drug resistance presents an ever-increasing global public health threat that involves all major microbial pathogens and antimicrobial drugs. The considerable concern regarding bacterial resistance to antimicrobial agents, bacterial adhesion, and proliferation has generated intense research in this field. Although urgently needed, an effective and long-lasting solution to this problem, i.e. microbial and especially bacterial colonization, has not yet been found. In the last decades, nanomaterials have attracted much attention because of their unique physical, chemical, and mechanical properties, due to their high surface area and size at the nanoscale. Owing to these extraordinary characteristics, nanomaterials are appropriate candidates for various applications in different fields such as medicine, pharmacy, food industry, etc. New strategies based on the use of nanomaterials such as nanoparticles, nanocapsules, nanogels, nanofibers, nanocomposites, or nanocoatings for controlling microbial virulence factors are very promising. In addition special focus recently is paid on nanostructured polymeric materials and nanocomposites with antimicrobial properties. The increasing attention within the scientific community regarding this topic can be easily assessed by searching the suitable keywords in some recognized literature databases. According to Scopus, in the last 10 years, more than 1,300 peer-reviewed documents have been published jointly containing keywords such as “nanocomposites” and “antimicrobial”. Interestingly, in the more specified search which refers to the utilization of nanostructured polymeric materials, it could be observed a similar profile i.e. growing tendency.

In this work porous commercially pure Ti substrates fabricated by spacer-holder technique (50 vol% NH4HCO3 and three range pores sizes, 100–200 μm, 250–355 μm and 355–500 μm) were coated with two types of gelatinous materials, one as a linear polymer (non-crosslinked) and another one crosslinked. The role of the crosslink, as well as the morphology, size and degree of interconnectivity of gelatins coatings on their tribo mechanical behavior (P-h curves and scratch tests) were analyzed. Results revealed a new promising route to manufacture composite porous implants which are potential candidates to develop new treatments, not only for osteochondral defects, but also for other types of damages involving tissues of different nature (hard and soft) perfectly joined. Ministry of Science and Innovation of Spain PID2019-109371GB-I00

Aim: Copper-doped mesoporous bioactive glass nanospheres (Cu- MBGN) are developed to ensure remineralization and antibacterial properties. This study investigated the influence of Cu-MBGN on resin composites' depth of cure (DoC). Materials and methods: Eight materials were tested in the study: giomer as a reference material (Beautifil II, Shofu) and seven experimental materials with 45% photoactive resin (60/40 BisGMA / TEGDMA) and 65% filler. Inert barium glass was combined with 10% Cu-MBGN, silica, or conventional 45S5 bioactive glass in the bimodal group. In the trimodal group, the fillers consisted of 0, 1, or 5% Cu- MBGN or 45S5 glass, silica, and inert silanized barium glass fillers. The materials were fed into 4 mm diameter and 10 mm high cylindrical molds and cured with 920 mW/cm2 for 20 s. The unpolymerized excess material was removed, the length of the remaining part was measured with a movable gauge and divided by 2 to obtain DoC according to ISO 4049. Data were statistically processed by one-way ANOVA and Tukey post-hoc test (p

For bioprinting, tailored bioinks combining tissue-like mechanical properties, printability and high biocompatibility are needed. The strategy of this project includes the precise characterization of the synthesis route and material properties, description of the printing process, as well as computing of flow and shear stress profile inside the printing needle. Furthermore, in vitro analyses using lentiviral fluorescent reporter cells were performed, which is a novel method that has so far hardly been used in biofabrication. The evaluation of the hydrogel and printing process for successful biofabrication is a multi-stage process and in our case demonstrated that ADA-GEL is a promising bioink., Transactions on Additive Manufacturing Meets Medicine, Vol 2 No 1 (2020): Trans. AMMM

Additive manufacturing of novel biomaterials with additional stimulating functions represents a promising strategy for bone repair. In this study, a systematic investigation of the necessary thermal post-treatment of 3D printed barium titanate composite ceramics to achieve the desired mechanical properties for bone regeneration is presented. The maximum sintering temperature was varied from 1320 °C to 1380 °C in 10 K intervals. After sintering, the samples were systematically characterized with respect to their porosity and mechanical properties. Specimens sintered at 1380 °C exhibit a considerably densified microstructure and improved mechanical integrity compared to specimens sintered at lower temperatures., Transactions on Additive Manufacturing Meets Medicine, Vol 2 No 1 (2020): Trans. AMMM

3D printing is a rapidly evolving field for biological (bioprinting) and non-biological applications. Due to a high degree of freedom for geometrical parameters in 3D printing, prototype printing of bioreactors is a promising approach in the field of Tissue Engineering. The variety of printers, materials, printing parameters and device settings is difficult to overview both for beginners as well as for most professionals. In order to address this problem, we designed a guidance including test bodies to elucidate the real printing performance for a given printer system. Therefore, performance parameters such as accuracy or mechanical stability of the test bodies are systematically analysed. Moreover, post processing steps such as sterilisation or cleaning are considered in the test procedure. The guidance presented here is also applicable to optimise the printer settings for a given printer device. As proof of concept, we compared fused filament fabrication, stereolithography and selective laser sintering as the three most used printing methods. We determined fused filament fabrication printing as the most economical solution, while stereolithography is most accurate and features the highest surface quality. Finally, we tested the applicability of our guidance by identifying a printer solution to manufacture a complex bioreactor for a perfused tissue construct. Due to its design, the manufacture via subtractive mechanical methods would be 21-fold more expensive than additive manufacturing and therefore, would result in three times the number of parts to be assembled subsequently. Using this bioreactor we showed a successful 14-day-culture of a biofabricated collagen-based tissue construct containing human dermal fibroblasts as the stromal part and a perfusable central channel with human microvascular endothelial cells. Our study indicates how the full potential of biofabrication can be exploited, as most printed tissues exhibit individual shapes and require storage under physiological conditions, after the bioprinting process.

journal article

The ICIE16-bioactive glass (BG) (48.0 SiO2, 6.6 Na2O, 32.9 CaO, 2.5 P2O5, 10.0 K2O (wt %)) has been developed as an alternative to 45S5-BG, the original BG composition (45.0 SiO2, 24.5 Na2O, 24.5 CaO, 6.0 P2O5 (wt %)), with the intention of broadening the BG sintering window while maintaining bioactivity. Because there is a lack of reports on ICIE16-BG biological properties, the influence of ICIE16-BG on viability, proliferation, and osteogenic differentiation of human mesenchymal stromal cells (MSCs) was evaluated in direct comparison to 45S5-BG in this study. The BGs underwent heat treatment similar to that which is required in order to fabricate scaffolds by sintering, which resulted in crystallization of 45S5-BG (45S5-CBG) while ICIE16 remained amorphous. Granules based on both BGs were biocompatible, but ICIE16-BG was less harmful to cell viability, most likely due to a more pronounced pH alkalization in the 45S5-CBG group. ICIE16-BG outperformed 45S5-CBG in terms of osteogenic differentiation at the cellular level, as determined by the increased activity of alkaline phosphatase. However, granules from both BGs were comparable regarding the stimulation of expression levels of genes encoding for osseous extracellular matrix (ECM) proteins. The addition of therapeutically active ions to ICIE16-BG might further improve its ability to stimulate ECM production and should be investigated in upcoming studies.

The objective of this study was to produce antibacterial poly(&epsilon, caprolactone) (PCL)-gelatin (GEL) electrospun nanofiber mats containing clove essential oil (CLV) using glacial acetic acid (GAA) as a &ldquo, benign&rdquo, (non-toxic) solvent. The addition of CLV increased the fiber diameter from 241 &plusmn, 96 to 305 &plusmn, 82 nm. Aside from this, the wettability of PCL-GEL nanofiber mats was increased by the addition of CLV. Fourier-transform infrared spectroscopy (FTIR) analysis confirmed the presence of CLV, and the actual content of CLV was determined by gas chromatography&ndash, mass spectrometry (GC-MS). Our investigations showed that CLV-loaded PCL-GEL nanofiber mats did not have cytotoxic effects on normal human dermal fibroblast (NHDF) cells. On the other hand, the fibers exhibited antibacterial activity against Staphylococcus aureus and Escherichia coli. Consequently, PCL-GEL/CLV nanofiber mats are potential candidates for antibiotic-free wound healing applications.

Efforts in tissue engineering aim at creating scaffolds that mimic the physiological environment with its structural, topographical and mechanical properties for restoring the function of damaged tissue. In this study we introduce composite fibres made by a biodegradable poly(lactic acid) (PLLA) matrix embedding bioactive silica-based glass particles (SBA2). Electrospinning is performed to achieve porous PLLA filaments with uniform dispersion of bioactive glass powder. The obtained composite fibres show in aligned arrays significantly increased elastic modulus compared with that of neat polymer fibres during uniaxial tensile stress. Additionally, the SBA2 bioactivity is preserved upon encapsulation as highlighted by the promoted deposition of hydroxycarbonate apatite (HCA) upon immersion in simulated body fluid solutions. HCA formation is sequential to earlier processes of polymer erosion and ion release leading to acidification of the surrounding solution environment. These findings suggest PLLA-SBA2 fibres as a composite, multifunctional system which might be appealing for both bone and soft tissue engineering applications. © 2019 by the authors.

Background: Up to today, animal studies are the gold standard for preclinical testing of new therapeutics for cutaneous wound healing. Alternative in vitro studies are mostly restricted to 2D cell cultures and thus only poorly reflect the complex physiological wound situation. Methods: To overcome this limitation, we present two 3D models based on human primary cells for studying different stages of cutaneous wound healing in vitro. For observation of the reepithelialization, human epidermal models are wounded locally using a biopsy punch and wound healing is monitored. We introduce impedance spectroscopy as a method to determine the efficacy of wound healing non‐destructively via the skin barrier. Results are compared to phase‐contrast microscopy, laser scanning and histology images as well as metabolic activity. For allowing the integration and analysis of deeper wounds, we expanded the models to full thickness skin equivalents with a collagen‐based extracellular matrix including fibroblasts. Results: Upon wounding, the impedance of epidermal models with initial values between 6.3 and 11.4kOcm2 dropped significantly by ‐95%. During on‐line monitoring over fourteen days the barrier recovered, indicated by significant increases in the impedance back to levels between 7.9 and 14.8kOcm2. For full thickness skin equivalents, too, this proved to be a promising screening technique with impedances starting at 276Ocm2 and dropping by ‐63% following wounding. With ongoing wound closure, the barrier recovered to 310Ocm2. Reepithelialization appeared to be donor dependent for both models, correlating well with results from imaging techniques and metabolic activity. Conclusions: Altogether, impedance analysis allows for rapid screening and evaluation of test substances and wound therapies, whereby only a small set of models is needed, cutting the costs of preclinical studies. Finally, with the help of these in vitro models, the amount of animals used in preclinical studies could be reduced.

Standard treatment for bone defects is the biological reconstruction using autologous bone—a therapeutical approach that suffers from limitations such as the restricted amount of bone available for harvesting and the necessity for an additional intervention that is potentially followed by donor-site complications. Therefore, synthetic bone substitutes have been developed in order to reduce or even replace the usage of autologous bone as grafting material. This structured review focuses on the question whether calcium phosphates (CaPs) and bioactive glasses (BGs), both established bone substitute materials, show improved properties when combined in CaP/BG composites. It therefore summarizes the most recent experimental data in order to provide a better understanding of the biological properties in general and the osteogenic properties in particular of CaP/BG composite bone substitute materials. As a result, BGs seem to be beneficial for the osteogenic differentiation of precursor cell populations in-vitro when added to CaPs. Furthermore, the presence of BG supports integration of CaP/BG composites into bone in-vivo and enhances bone formation under certain circumstances.

Reproductive tissue engineering (REPROTEN) has been recently defined as the application of the tissue engineering approach targeting reproductive organs and several research works are focusing on this novel strategy. Being still an innovative field, most of the scaffold characterization techniques suitable for other tissue targets give inappropriate results, and there is the need to evaluate and investigate novel approaches. In particular the focus of this paper is the evaluation of the infiltration of ovarian follicles inside patterned electrospun scaffolds. Beyond the standard techniques, for the first time the use of magnetic resonance imaging (MRI) for this purpose is proposed and specific protocols for scaffold preparation are reported. Positive results in terms of evaluation of scaffolds incorporating follicles confirm this technique as highly effective for further applications in this field.

Mesoporous bioactive glasses – Biological response, {"references":["Thrivikraman G., Madras G., Basu B. In vitro/In vivo assessment and mechanisms of toxicity of bioceramics materials and its wear particulates, RSC Adv., 2014, 4, 12763-12781.","Wallin R.F., Arscott E.F., A Practical Guide to ISO 10993-5: Cytotoxicity, Medical Device and Diagnostic Industry, 1998, 4.","ISO DOCUMENT 10993-5. Biological evaluation of medical devices, Part 5, Tests for cytotoxicity: in vitro methods, 1992."]}

A traditional technique for obtaining 3D bioactive glass scaffolds with bone like structure, {"references":["1) A. A. El-Rashidy, J. A. Roether, L. Harhaus, U. Kneser, A. R. Boccaccini, ActaBiomater 62 (2017) 1-28.","2) P. Balasubramanian, T. Buttner, V. M. Pacheco, A. R. Boccaccini, J. Eur. Cer. Soc. 38 (3), (2018) 855-869.","3) M. Jabbari, R. Bulatova, A.I.Y Tok, C.R.H. Bahl, E. Mitsoulis, J.H. Hattel, Mat. Sci. Eng-B 212 (2016) 39-61.","4) T. Kokubo, H. Takadama, Biomaterials 27 (2006) 2907-2915"]}

Fragestellung: Dreidimensionale (3D) Scaffolds aus bioaktivem Glas (BG) des Typs 45S5 finden erfolgreichen Einsatz in Knochendefekten und unterstützen die knöcherne Regeneration. Dabei korreliert das Zusammenwirken von Oberflächencharakteristik, Porosität sowie mechanischen Gegebenheiten[zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2018)

Alginate dialdehyde (ADA), gelatin, and nano-scaled bioactive glass (nBG) particles are being currently investigated for their potential use as three-dimensional scaffolding materials for bone tissue engineering. ADA and gelatin provide a three-dimensional scaffold with properties supporting cell adhesion and proliferation. Combined with nanocristalline BG, this composition closely mimics the mineral phase of bone. In the present study, rat bone marrow derived mesenchymal stem cells (MSCs), commonly used as an osteogenic cell source, were evaluated after encapsulation into ADA-gelatin hydrogel with and without nBG. High cell survival was found in vitro for up to 28 days with or without addition of nBG assessed by calcein staining, proving the cell-friendly encapsulation process. After subcutaneous implantation into rats, survival was assessed by DAPI/TUNEL fluorescence staining. Hematoxylin-eosin staining and immunohistochemical staining for the macrophage marker ED1 (CD68) and the endothelial cell marker lectin were used to evaluate immune reaction and vascularization. After in vivo implantation, high cell survival was found after 1 week, with a notable decrease after 4 weeks. Immune reaction was very mild, proving the biocompatibility of the material. Angiogenesis in implanted constructs was significantly improved by cell encapsulation, compared to cell-free beads, as the implanted MSCs were able to attract endothelial cells. Constructs with nBG showed higher numbers of vital MSCs and lectin positive endothelial cells, thus showing a higher degree of angiogenesis, although this difference was not significant. These results support the use of ADA/gelatin/nBG as a scaffold and of MSCs as a source of osteogenic cells for bone tissue engineering. Future studies should however improve long term cell survival and focus on differentiation potential of encapsulated cells in vivo.

Highly porous 45S5 bioactive glass-based scaffolds were fabricated by the foam replica technique and coated with collagen by a novel method. After an initial cleaning step of the bioactive glass surface to expose reactive &ndash, OH groups, samples were surface functionalized by (3-aminopropyl)triethoxysilane (APTS). Functionalized scaffolds were immersed in a collagen solution, left for gelling at 37 &deg, C, and dried at room temperature. The collagen coating was further stabilized by crosslinking with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS). Applying this coating method, a layer thickness of a few micrometers was obtained without affecting the overall scaffold macroporosity. In addition, values of compressive strength were enhanced by a factor of five, increasing from 0.04 &plusmn, 0.02 MPa for uncoated scaffolds to 0.18 &plusmn, 0.03 MPa for crosslinked collagen-coated scaffolds. The composite material developed in this study exhibited positive cell (MG-63) viability as well as suitable cell attachment and proliferation on the surface. The combination of bioactivity, mechanical competence, and cellular response makes this novel scaffold system attractive for bone tissue engineering.

The European steel industry generated about 21.4 million tons of slag in 2012 resulting from steel making. About 24% is not being reused, representing a severe environmental problem in Europe, but also a huge amount of available material. Utilization of currently landfilled waste is a target of growing interest towards circular economy and closing the loop.

Harald Unterweger,1 László Dézsi,2,3 Jasmin Matuszak,1 Christina Janko,1 Marina Poettler,1 Jutta Jordan,4 Tobias Bäuerle,4 János Szebeni,2,3 Tobias Fey,5 Aldo R Boccaccini,6 Christoph Alexiou,1 Iwona Cicha1 1ENT Department, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, Universitätsklinikum Erlangen, Erlangen, Germany; 2Nanomedicine Research and Education Center, Institute of Pathophysiology, Semmelweis University, Budapest, Hungary; 3SeroScience Ltd., Budapest, Hungary; 4Institute of Radiology, Preclinical Imaging Platform Erlangen, Universitätsklinikum Erlangen, Erlangen, Germany; 5Institute of Glass and Ceramics, Department of Materials Science and Engineering, University Erlangen-Nuremberg, Erlangen, Germany; 6Institute of Biomaterials, Department of Materials Science and Engineering, University Erlangen-Nuremberg, Erlangen, Germany 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 (SPIONDex) 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, SPIONDex displayed no irritation potential in a chick chorioallantoic membrane assay. Cell uptake studies of ultra-small (30nm) SPIONDex confirmed their internalization by macrophages, but not by non-phagocytic cells. Additionally, complement activation-related pseudoallergy (CARPA) experiments in pigs treated with ultra-small SPIONDex indicated the absence of hypersensitivity reactions. Conclusion: These results emphasize the exceptional safety of SPIONDex, setting them apart from the existing SPION-based contrast agents and making them a very promising candidate for further clinical development. Keywords: CARPA, cross-linking, irritation potential, MRI, SPION, storage stability

The European steel industry generated in 2012 about 21.4 million tons of slag of which about 24% was landfilled. Landfilling of the huge amount of materials poses a severe environmental problem in Europe. Utilization of currently landfilled waste is a target of growing interest towards circular economy and closing the loop. Insulating refractory materials are needed in all thermal energy intensive industries for example in the construction of the furnaces, kilns, incinerators, or reactors. The relevant properties of certain slags and industrial by-products to withstand high temperatures make them possible raw material candidates when manufacturing novel refractory materials. In the presented study, exploitation potentiality of ferrochrome slag and other by-product as raw material asset for refractory materials has been studied. The goal was to maximize the use of secondary raw materials in refractory materials with mechanical and chemical resistance up to 1200°C in gaseous atmosphere. Recipes were formulated based on raw material characterization results and theoretical calculations including optimal particle packing calculations. Mortar pieces were prepared according to standard EN 196-1. Mechanical properties of the refractory specimens were evaluated based on their cold crushing strength. In addition, specimens were characterized in terms of physical and thermo-physical properties: density, porosity, thermal conductivity, thermal diffusivity and heat capacity and compared to commercially available refractory material. The cold compressive strengths reaching the values of 70-90 MPa were observed for the mortars heat-treated at 1200°C being comparable level to commercial reference. Thermal conductivity values of the mortars were at the level of 1.8-2.2 W/K m, which indicates good heat insulating capability showing valueseven below that of reference material.

Commercial pure titanium is a recognized and accepted material for cortical bone tissue substitution. However, stress-shielding phenomena and lack of osseointegration result in significant limitations. This work is focused on the achievement of an effective solution for both problems via fabrication of porous titanium substrates coated with bioactive glass. Substrates were obtained through the space holder technique giving values of stiffness and yield strength compatible with cortical bone tissue to reduce the stress-shielding phenomenon. Titanium substrates were coated with different number of layers of bioactive glass 45S5 by dripping sedimentation. The substrates porosity was characterized by different techniques. Ultrasound, compression and micro-mechanical testing were used for mechanical properties evaluation. After substrates coating, the infiltration ability, coating homogeneity and structural integrity (chipping and cracking) were evaluated for each coating layer. The chemical composition of coating and phases were studied before and after in vitro tests in Simulated Body Fluid. The results showed more homogenous coating, adherence and greater hydroxyapatite growth for the tri-layer system in both dense and porous samples. Besides, the relation of Ca/P was closed to that of stoichiometric hydroxyapatite in the human body. The coated porous titanium could be potentially used in load bearing partial implants with improved osseointegration. Ministry of Economy and Competitiveness of the State General Administration of Spain grant MAT2015-71284-P

Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted great attention in many biomedical fields and are used in preclinical/experimental drug delivery, hyperthermia and medical imaging. In this study, biocompatible magnetite drug carriers, stabilized by a dextran shell, were developed to carry tissue plasminogen activator (tPA) for targeted thrombolysis under an external magnetic field. Different concentrations of active tPA were immobilized on carboxylated nanoparticles through carbodiimide-mediated amide bond formation. Evidence for successful functionalization of SPIONs with carboxyl groups was shown by Fourier transform infrared spectroscopy. Surface properties after tPA immobilization were altered as demonstrated by dynamic light scattering and ζ potential measurements. The enzyme activity of SPION-bound tPA was determined by digestion of fibrin-containing agarose gels and corresponded to about 74% of free tPA activity. Particles were stored for three weeks before a slight decrease in activity was observed. tPA-loaded SPIONs were navigated into thrombus-mimicking gels by external magnets, proving effective drug targeting without losing the protein. Furthermore, all synthesized types of nanoparticles were well tolerated in cell culture experiments with human umbilical vein endothelial cells, indicating their potential utility for future therapeutic applications in thromboembolic diseases.

The engineering of vascular grafts is a growing field in regenerative medicine. Although numerous attempts have been made, the current vascular grafts made of polyurethane (PU), Dacron®, or Teflon® still display unsatisfying results. Electrospinning of biopolymers and native proteins has been in the focus of research to imitate the extracellular matrix (ECM) of vessels to produce a small caliber, off-the-shelf tissue engineered vascular graft (TEVG) as a substitute for poorly performing PU, Dacron, or Teflon prostheses. Blended poly-ε-caprolactone (PCL)/collagen grafts have shown promising results regarding biomechanical and cell supporting features. In order to find a suitable PCL/collagen blend, we fabricated plane electrospun PCL scaffolds using various collagen type I concentrations ranging from 5% to 75%. We analyzed biocompatibility and morphological aspects in vitro. Our results show beneficial features of collagen I integration regarding cell viability and functionality, but also adverse effects like the loss of a confluent monolayer at high concentrations of collagen. Furthermore, electrospun PCL scaffolds containing 25% collagen I seem to be ideal for engineering vascular grafts.

Due to the presence of tripeptide arginine–glycine–aspartic acid, gelatin is considered a very promising additive material to improve the cytocompatibility of alginate-based hydrogels. Two different strategies, physical blending and chemical crosslinking with gelatin, are used in this study to modify alginate hydrogel. As the intermolecular interactions between the polysaccharide and protein in the resulting physically blended and chemically crosslinked hydrogels are different, significant differences in the properties of these hydrogel types, regarding especially their surface topography, degradation kinetics, mechanical properties, and protein release behavior, are observed. Cellular behavior on both types of alginate–gelatin hydrogels is investigated using primary human dermal fibroblasts to elucidate the effects of the different structural, mechanical, and degradation properties of the produced hydrogels on fibroblast attachment and growth. The hydrogel that is chemically crosslinked with gelatin exhibits the highest degree of cytocompatibility regarding adhesion, proliferation, metabolic activity, and morphology of growing fibroblasts.

Harald Unterweger,1,* Christina Janko,1,* Marc Schwarz,2 László Dézsi,3 Rudolf Urbanics,4 Jasmin Matuszak,1 Erik Őrfi,3 Tamás Fülöp,3 Tobias Bäuerle,2 János Szebeni,3,4 Clément Journé,5 Aldo R Boccaccini,6 Christoph Alexiou,1 Stefan Lyer,1 Iwona Cicha1 1Cardiovascular Nanomedicine Unit, Section of Experimental Oncology und Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, ENT Department, University Hospital Erlangen, Friedrich-Alexander-Universitaet Erlangen-Nuernberg, 2Preclinical Imaging Platform Erlangen (PIPE), Institute of Radiology, University Hospital Erlangen, Erlangen, Germany; 3Nanomedicine Research and Education Center, Semmelweis University, 4SeroScience Ltd., Budapest, Hungary; 5Inserm U1148, Fédération de Recherche en Imagerie Multimodalités (FRIM), X Bichat Hospital, Paris Diderot University, Paris, France; 6Institute of Biomaterials, Department of Materials Science and Engineering, University Erlangen-Nuremberg, Erlangen, Germany *These authors contributed equally to this work Abstract: Iron oxide-based contrast agents have been in clinical use for magnetic resonance imaging (MRI) of lymph nodes, liver, intestines, and the cardiovascular system. Superparamagnetic iron oxide nanoparticles (SPIONs) have high potential as a contrast agent for MRI, but no intravenous iron oxide-containing agents are currently approved for clinical imaging. The aim of our work was to analyze the hemocompatibility and immuno-safety of a new type of dextran-coated SPIONs (SPIONdex) and to characterize these nanoparticles with ultra-high-field MRI. Key parameters related to nanoparticle hemocompatibility and immuno-safety were investigated in vitro and ex vivo. To address concerns associated with hypersensitivity reactions to injectable nanoparticulate agents, we analyzed complement activation-related pseudoallergy (CARPA) upon intravenous administration of SPIONdex in a pig model. Furthermore, the size-tunability of SPIONdex and the effects of size reduction on their biocompatibility were investigated. In vitro, SPIONdex did not induce hemolysis, complement or platelet activation, plasma coagulation, or leukocyte procoagulant activity, and had no relevant effect on endothelial cell viability or endothelial–monocytic cell interactions. Furthermore, SPIONdex did not induce CARPA even upon intravenous administration of 5 mg Fe/kg in pigs. Upon SPIONdex administration in mice, decreased liver signal intensity was observed after 15 minutes and was still detectable 24 h later. In addition, by changing synthesis parameters, a reduction in particle size

Ti6Al4V has been extensively studied in orthopedic applications because of its biocompatibility, desirable mechanical strength, and fatigue resistance. A wide range of bioinert ceramics have been investigated to further develop the tribological and mechanical properties of Ti6Al4V for the production of potential femoral heads. However, an analysis of the literature indicates that the performance of the coatings produced has been inconsistent. In this review, for the first-time deposition techniques of the most widely studied bioinert ceramics namely nitrides, carbides, zirconia, and alumina on Ti6Al4V substrates and their relevant mechanical and tribological performance have been analyzed. Finally, graphene has also been suggested for use together with bioinert ceramics due to its excellent mechanical and physical properties for coating Ti6Al4V femoral heads.