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The occurrence of periprosthetic femoral fractures (PFF) has increased in people with osteoporosis due to decreased bone density, poor bone quality, and stress shielding from prosthetic implants. PFF treatment in the elderly is a genuine concern for orthopaedic surgeons as no effective solution currently exists. Therefore, the goal of this study was to determine whether the design of a novel advanced medicinal therapeutic device (AMTD) manufactured from a polymeric blend in combination with a fracture fixation plate in the femur is capable of withstanding physiological loads without failure during the bone regenerative process. This was achieved by developing a finite element (FE) model of the AMTD together with a fracture fixation assembly, and a femur with an implanted femoral stem. The response of both normal and osteoporotic bone was investigated by implementing their respective material properties in the model. Physiological loading simulating the peak load during standing, walking, and stair climbing was investigated. The results showed that the fixation assembly was the prime load bearing component for this configuration of devices. Within the fixation assembly, the bone screws were found to have the highest stresses in the fixation assembly for all the loading conditions. Whereas the stresses within the AMTD were significantly below the maximum yield strength of the device's polymeric blend material. Furthermore, this study also investigated the performance of different fixation assembly materials and found Ti-6Al-4V to be the optimal material choice from those included in this study.

Bioprinting has been advancing in the field of tissue engineering as the process for fabricating scaffolds, making use of additive manufacturing technologies. In situ bioprinting (also termed intraoperative bioprinting) is a promising solution to address the limitations of conventional bioprinting approaches. This article discusses the main approaches and technologies for in situ bioprinting. It provides a brief overview of the bioprinting pipeline, highlighting possible solutions to improve currently used approaches. Additionally, case studies of in situ bioprinting are provided and in situ bioprinting future perspectives are discussed.

Tissue engineering (TE) is an interdisciplinary field that was introduced from the necessity of finding alternative approaches to transplantation for the treatment of damaged and diseased organs or tissues. Unlike the conventional procedures, TE aims at inducing the regeneration of injured tissues through the implantation of customized and functional engineered tissues, built on the so-called ‘scaffolds’. These provide structural support to cells and regulate the process of new tissue formation. The properties of the scaffold are essentials, and they can be controlled by varying the biomaterial formulation and the fabrication technology used to its production. Pectin is emerging as an alternative biomaterial to non-degradable and high-cost petroleum-based biopolymers commonly used in this field. It shows several promising properties including biocompatibility, biodegradability, non-toxicity and gelling capability. Pectin-based formulations can be processed through different fabrication approaches into bidimensional and three-dimensional scaffolds. This chapter aims at highlighting the potentiality in using pectin as biomaterial in the field of tissue engineering. The most representative applications of pectin in preparing scaffolds for wound healing and tissue regeneration are discussed.

Simple Summary Alterations of the composition and architecture of the extracellular matrix (ECM), leading to increased stiffness, is known to condition development, invasiveness and severity of neoplasms. In this study, we report increased lymph node (LN) stiffness in human lymphomas, measured by LN elastometry or by computerized imaging of bioptic specimens. Stiffness matched to lymphoma histotype and grading. The enzyme lysyl oxidase (LOX) is involved in the rise of collagen cross-linking in Hodgkin lymphomas, while altered architecture, shown by scanning electron microscopy and polarized light microscopy is involved in advanced follicular lymphomas. Based on these data, digital pathology may help in the staging of lymphomas, and lysyl oxidase may represent a target for therapy in Hodgkin lymphomas. Abstract Purpose: The biochemical composition and architecture of the extracellular matrix (ECM) is known to condition development and invasiveness of neoplasms. To clarify this point, we analyzed ECM stiffness, collagen cross-linking and anisotropy in lymph nodes (LN) of Hodgkin lymphomas (HL), follicular lymphomas (FL) and diffuse large B-cell lymphomas (DLBCL), compared with non-neoplastic LN (LDN). Methods and Results: We found increased elastic (Young’s) modulus in HL and advanced FL (grade 3A) over LDN, FL grade 1–2 and DLBCL. Digital imaging evidenced larger stromal areas in HL, where increased collagen cross-linking was found; in turn, architectural modifications were documented in FL3A by scanning electron microscopy and enhanced anisotropy by polarized light microscopy. Interestingly, HL expressed high levels of lysyl oxidase (LOX), an enzyme responsible for collagen cross-linking. Using gelatin scaffolds fabricated with a low elastic modulus, comparable to that of non-neoplastic tissues, we demonstrated that HL LN-derived mesenchymal stromal cells and HL cells increased the Young’s modulus of the extracellular microenvironment through the expression of LOX. Indeed, LOX inhibition by β-aminopropionitrile prevented the gelatin stiffness increase. Conclusions: These data indicate that different mechanical, topographical and/or architectural modifications of ECM are detectable in human lymphomas and are related to their histotype and grading.

Developing green and nontoxic biomaterials, derived from renewable sources and processable through 3D bioprinting technologies, is an emerging challenge of sustainable tissue engineering. Here, pectin from citrus peels was cross-linked for the first time with (3-glycidyloxypropyl)trimethoxysilane (GPTMS) through a one-pot procedure. Freeze-dried porous pectin sponges, with tunable properties in terms of porosity, water uptake, and compressive modulus, were obtained by controlling GPTMS content. Cell experiments showed that GPTMS did not affect the cytocompatibility of pectin. The addition of GPTMS improved the printability of pectin due to an increase of viscosity and yield stress. Three-dimensional woodpile and complex anatomical-shaped scaffolds with interconnected micro- and macropores were, therefore, bioprinted without the use of any additional support material. These results show the great potential of using pectin cross-linked with GPTMS as biomaterial ink to fabricate patient-specific scaffolds, which could be used to promote tissue regeneration in vivo.

Developing biomaterial formulations with specific biochemical characteristics and physical properties suitable for bioprinting of 3D scaffolds is a pivotal challenge in tissue engineering. Therefore, the design of novel bioprintable formulations is a continuously evolving research field. In this work, the authors aim at expanding the library of biomaterial inks by blending two natural biopolymers: pectin and gelatin. Cytocompatible formulations are obtained by combining pectin and gelatin at different ratios and using (3-glycidyloxypropyl)trimethoxysilane (GPTMS) as single crosslinking agent. It is shown that the developed formulations are all suitable for extrusion-based 3D bioprinting. Self-supporting scaffolds with a designed macroporosity and micropores in the bioprinted struts are successfully obtained by combining extrusion-based bioprinting and freeze-drying. The presence of gelatin in these formulations allows for the modulation of porosity, of water uptake and of scaffold stiffness in respect to pure pectin scaffolds. Results demonstrate that these new biomaterial formulations, processed with this specific approach, are promising candidates for the fabrication of tissue-like scaffolds for tissue regeneration.

Poultry feathers are among the most abundant and polluting keratin-rich waste biomasses. In this work, we developed a one-pot microwave-assisted process for eco-friendly keratin extraction from poultry feathers followed by a direct electrospinning (ES) of the raw extract, without further purification, to obtain keratin-based bioplastics. This microwave-assisted keratin extraction (MAE) was conducted in acetic acid 70% v/v. The effects of extraction time, solvent/feathers ratio, and heating mode (MAE vs. conventional heating) on the extraction yield were investigated. The highest keratin yield (26 ± 1% w/w with respect to initial feathers) was obtained after 5 h of MAE. Waste-derived keratin were blended with gelatin to fabricate keratin-based biodegradable and biocompatible bioplastics via ES, using 3-(Glycidyloxypropyl)trimethoxysilane (GPTMS) as a cross-linking agent. A full characterization of their thermal, mechanical, and barrier properties was performed by differential scanning calorimetry, thermogravimetric analysis, uniaxial tensile tests, and water permeability measurements. Their morphology and protein structure were investigated using scanning electron microscopy and attenuated total reflection-infrared spectroscopy. All these characterizations highlighted that the properties of the keratin-based bioplastics can be modulated by changing keratin and GPTMS concentrations. These bioplastics could be applied in areas such as bio-packaging and filtration/purification membranes.

Fungal contamination poses at risk the whole food production chain - from farm to fork - with potential negative impact on human health. So far, the insurgence of pathogens has been restrained by the use of chemical compounds, whose residues have gradually accumulated determining toxic effects in the environment. Modern innovative techniques imply the use of natural and eco-sustainable bioactive plant molecules as pathogens and pests-control agents. These may be profitably recovered in large amounts at the end of industrial milling processes. This is the case of the non- digestible hull of common buckwheat (Fagopyrum esculentum Moench), a natural source of polyphenols, tocopherols, phytosterols and fatty acids. We extract these compounds from the hull of buckwheat ; apply them to Aspergillus flavus - aflatoxin producer - under in vitro conditions, checking their ability to inhibit fungal growth and aflatoxin biosynthesis. Moreover, a solvent free method implying the adoption of supercritical CO2 as solvent was set up to extract lipophilic molecules from the buckwheat’ hulls. Positive results in controlling fungal growth and aflatoxin biosynthesis let infer that the extracts could be further tested also under in vivo conditions.

Extrusion-based three-dimensional (3D) bioprinting is nowadays the most efficient additive manufacturing technology to fabricate well-defined and clinical-scale relevant 3D scaffolds, exploiting soft biomaterials. However, trial and error approaches are usually employed to achieve the desired structures, thus leading to a waste of time and material. In this work, we show the potential of finite element (FE) simulation in predicting the printability of a biomaterial, in terms of extrudability and scaffold mechanical stability over time. To this end, we firstly rheologically characterized a newly developed self-assembling peptide hydrogel (SAPH). Subsequently, we modelled both the extrusion process of the SAPHs as well as the stability over time of a 3D bioprinted wood-pile scaffold. FE modelling revealed that the simulated SAPHs and printing set-ups led to a successful extrusion, within a range of shear stresses that are not detrimental for cells. Finally, we successfully 3D bioprinted a human ear-shaped scaffolds with in vivo dimensions and several protrusion planes by bioplotting the SAPH into a poly(vinyl alcohol)-poly(vinyl pyrrolidone) copolymer, which was identified as a suitable bioprinting strategy by mechanical FE simulation.

Extrusion-based three-dimensional (3D) bioprinting is nowadays the most efficient additive manufacturing technology to fabricate well-defined and clinical-scale relevant 3D scaffolds, exploiting soft biomaterials. However, trial and error approaches are usually employed to achieve the desired structures, thus leading to a waste of time and material. In this work, we show the potential of finite element (FE) simulation in predicting the printability of a biomaterial, in terms of extrudability and scaffold mechanical stability over time. To this end, we firstly rheologically characterized a newly developed self-assembling peptide hydrogel (SAPH). Subsequently, we modelled both the extrusion process of the SAPHs as well as the stability over time of a 3D bioprinted wood-pile scaffold. FE modelling revealed that the simulated SAPHs and printing set-ups led to a successful extrusion, within a range of shear stresses that are not detrimental for cells. Finally, we successfully 3D bioprinted a human ear-shaped scaffolds with in vivo dimensions and several protrusion planes by bioplotting the SAPH into a poly(vinyl alcohol)-poly(vinyl pyrrolidone) copolymer, which was identified as a suitable bioprinting strategy by mechanical FE simulation.

One of the main challenges of the interface-tissue engineering is the regeneration of diseased or damaged interfacial native tissues that are heterogeneous both in composition and in structure. In order to achieve this objective, innovative fabrication techniques have to be investigated. This work describes the design, fabrication, and validation of a novel mixing system to be integrated into a double-extruder bioprinter, based on an ultrasonic probe included into a mixing chamber. To validate the quality and the influence of mixing time, different nanohydroxyapatite–gelatin samples were printed. Mechanical characterization, micro-computed tomography, and thermogravimetric analysis were carried out. Samples obtained from three-dimensional bioprinting using the mixing chamber were compared to samples obtained by deposition of the same final solution obtained by manually operated ultrasound probe, showing no statistical differences. Results obtained from samples characterization allow to consider the proposed mixing system as a promising tool for the fabrication of graduated structures which are increasingly being used in interface-tissue engineering.

The aim of this work is to design a robotic bioprinting platform able to fabricate a three-dimensional structure onto irregular surfaces. With respect to the limitations of current in vitro bioprinting approach, widely used in scaffold-based tissue engineering – handling difficulty, risk of contamination, shape not matching with the defect site – this robotic bioprinter can offer an innovative solution allowing in situ bioprinting, a direct dispensing of biological materials onto and into the damaged site. The robotic platform was developed starting from the 5 degrees-of-freedom open source MOVEO robot from BCN3D. The hardware and the software of the original project were re-engineered to control the robot using LinuxCNC, a path planning algorithm was developed in Matlab®, and the end-effector was equipped with a pneumatic extruder. The algorithm automatically projects any generic printing pattern on the surface on which the scaffold will be 3D bioprinted. For each point, the algorithm calculates the joint angles to keep the end effector always perpendicular to the surface. A g-code file is then exported to Linux CNC adding parameters to control the air pressure and the printing speed. The robotic platform was tested to evaluate its performances. Resolution (~200 ​μm) and repeatability were estimated and preliminary in situ bioprinting tests were performed onto different irregular surfaces, including a physiologically relevant bone model.

Field commodities are exposed to fungal contamination with potential negative impact on human health. Bioactive plant molecules, as for example antioxidant compounds present in common buckwheat (Fagopyrum esculentum Moench), can provide natural means of biocontrol. To this purpose, the ability of flavonols extracted from common buckwheat hull to modulate, in in vitro conditions, Aspergillus flavus production of aflatoxin B1 (AFB1) was tested in comparison to synthetic rutin. Positive results achieved let infer that the extract could be furtherly tested also in vivo. Copyright� (2017) by the International Measurement Confederation (IMEKO). All rights reserved.

Besides its use in the brewing industry, hop cones appear as a powerful source of biologically active compounds, already checked for their putative anticancer, antimicrobial, and other bioactivities. Conversely, hop use in pest control remains to date under-investigated. Therefore, the biological activity of hop essential oil (EO) and its main constituents was investigated here against Sitophilus granarius. Adult contact toxicity was found 24 h after treatment with hop EO (LD50/LD90 13.30/40.23 &micro, g/adult), and its three most abundant components, &alpha, humulene, &beta, myrcene, and &beta, caryophyllene (LD50/LD90 41.87/73.51, 75.91/126.05, and 138.51/241.27 &micro, g/adult, respectively), negligible variations at 48 h, except for &alpha, humulene (LD50/LD90 26.83/49.49 &micro, g/adult), were found. The fumigant toxicity of the EO and terpenes was also checked: in the absence of wheat grains, &beta, myrcene showed the highest inhalation toxicity (LC50/LC90 72.78/116.92 mg/L air), whereas &alpha, caryophyllene, and the EO induced similar values (LC50/LC90 about 130/200 mg/L air), with the exception for EO, the wheat presence increased (30&ndash, 50%) LC50/LC90 values. Moreover, EO and terpenes were perceived by insect antennae and elicited repellent activity. Only &beta, caryophyllene showed an anticholinesterase effect, this suggesting that different mechanisms of action should be responsible for hop EO toxicity. Therefore, hop EO appears suitable for developing control means against this pest.

In this article we present an upgraded design of the existing push–pull hydrostatically coupled dielectric elastomer actuator (HC-DEA) for use in the field of soft manipulators. The new design has segmented electrodes, which stand as four independent elements on the active membrane of the actuator. When properly operated, the actuator can generate both out of plane and in-plane motions resulting in a multi-degrees of freedom soft actuator able to exert both normal pushes (like a traditional HC-DEA) and tangential thrusts. This novel design makes the actuator suitable for delicate flat object transportation. In order to use the actuator in soft systems, we experimentally characterized its electromechanical transduction and modeled its contact mechanics. Finally, we show that the proposed actuator can be employed as a modular unit to develop active surfaces for flat object roto-translation.