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In the field of tissue regeneration, the lack of a stable endothelial lining may affect the hemocompatibility of both synthetic and biological replacements. These drawbacks might be prevented by specific biomaterial functionalization to induce selective endothelial cell (EC) adhesion. Decellularized bovine pericardia and porcine aortas were selectively functionalized with a REDV tetrapeptide at 10−5 M and 10−6 M working concentrations. The scaffold-bound peptide was quantified and REDV potential EC adhesion enhancement was evaluated in vitro by static seeding of human umbilical vein ECs. The viable cells and MTS production were statistically higher in functionalized tissues than in control. Scaffold histoarchitecture, geometrical features, and mechanical properties were unaffected by peptide anchoring. The selective immobilization of REDV was effective in accelerating ECs adhesion while promoting proliferation in functionalized decellularized tissues intended for blood-contacting applications., Graphical abstract Image 1, Highlights • Covalent functionalization of the decellularized tissues with REDV peptide accelerates endothelialization. • New covalent grafting method not inducing collagen cross-linking. • Measurements through two photon miscroscopy allow the quantification of biological matrix bound peptide. • The decellularized tissues can be changed by chemical procedures to promote specific cellular behaviour with ECM preservation.

The paper presents a preliminary design activity and virtual prototyping of an innovative boat equipped with hydrofoils and hybrid propulsion, with the aim of extending the foil technology from the field of competition boats to recreational day-cruiser yachts and creating a craft with minimal environmental impact. Hydrofoils allow boats to rise from the water, greatly reducing resistance and increasing performance. The current work dealt with the preliminary design of a daysailer with foil technology and hybrid propulsion that allow to combine green and comfortable navigation both under sail and motor and that, when required, can sail in a more performing way by exploiting the foil technology and the thrust of the wind. After having deepened the theory and physics of sailing on foils, a MATLAB code was created to integrate the stability equations that characterize hydrofoil sailboats: connecting the acting forces and allowing to define the dimensions of the geometries, the code was fundamental in speeding up the iterative preliminary design process. The next step was to model the geometry of the hull and the appendages in the CAD environment and, subsequently, the wing movement mechanism so that it could both manage the incidence of the wings and retract the foils when the boat is moored. The hull, profiles, and wings were subsequently placed in a CFD and VPP virtual environment for testing their resistance. Future developments will include a detailed design and the physical prototyping of a first boat for water testing.

Over the past years, a wide range of dental implants has been proposed. In general, the dentists may find the best solutions according to the specific needs of the patients. A variety of factors influences the level of osseointegration and, consequently, the anchorage of the implant to the bone. The stress transfer mechanism along the bone-implant interface depends upon the surface area of the bone-implant contact. Great efforts have been devoted to the design of 3D porous lattice structures with tailored architectural features in order to reduce the implant stiffness as well as to favour bone ingrowth, thus stabilizing the device. Accordingly, the aim of the current study was to provide further insight into the design criteria for dental implants. In particular, starting from a screw implant (Implant A), different concepts of dental implants were developed: i) Implants B1–B5, with lattice shell surrounding a solid core, without thread; ii) Implant C, with lattice structure; iii) Implant D as topography optimized implant. Finite element analysis on the several models of bone-implant provided interesting information in terms of stress distributions in cortical and trabecular bone. Some differences among the implants may be ascribed to the different design criteria.

The aim of this study was to evaluate the effect of a time-dependent magnetic field on the biological performance of periodontal ligament stem cells (PDLSCs). A Western blot analysis and Alamar Blue assay were performed to investigate the proliferative capacity of magnetically stimulated PDLSCs (PDLSCs MAG) through the study of the MAPK cascade (p-ERK1/2). The observation of ALP levels allowed the evaluation of the effect of the magnetic field on osteogenic differentiation. Metabolomics data, such as oxygen consumption rate (OCR), extracellular acidification rate (ECAR) and ATP production provided an overview of the PDLSCs MAG metabolic state. Moreover, the mitochondrial state was investigated through confocal laser scanning microscopy. Results showed a good viability for PDLSCs MAG. Magnetic stimulation can activate the ERK phosphorylation more than the FGF factor alone by promoting a better cell proliferation. Osteogenic differentiation was more effectively induced by magnetic stimulation. The metabolic panel indicated significant changes in the mitochondrial cellular respiration of PDLSCs MAG. The results suggested that periodontal ligament stem cells (PDLSCs) can respond to biophysical stimuli such as a time-dependent magnetic field, which is able to induce changes in cell proliferation and differentiation. Moreover, the magnetic stimulation also produced an effect on the cell metabolic profile. Therefore, the current study demonstrated that a time-dependent magnetic stimulation may improve the regenerative properties of PDLSCs.

This chapter would represent a guide for the reader in the path that goes toward more recent and innovative approaches in bone tissue regeneration. Starting from an introduction on tissue engineering approaches and an overview on the scaffold fabrication methods and materials, the chapter will first provide concepts related to surface presentation and modification routes, finally approaching to the fascinating field of bioactive magnetic scaffolds. In this context, the basic principles of magnetism and magnetic materials will be reported, starting from a brief hint to current medical applications of magnetism, such as drug and gene delivery, hyperthermia treatment of tumors and radionuclide therapy, magneto-mechanical stimulation or activation of cell-constructs and mechanosensitive ion channels, magnetic cell-seeding procedures, and controlled cell proliferation and differentiation. The potential to design multifunctional and bioactive 3D structures for in situ and on-demand release of drugs and/or growth factors, as well as for advanced fixation systems, will be highlighted.

Titanium and its alloys are widely employed in commercial dental devices. Because the surface morphology and chemical composition of Ti-based dental implants play a relevant role in osseointegration, three different commercial threaded implants have been investigated by scanning electron microscopy and X-ray photoelectron spectroscopy (XPS). The Implants A and C were made of pure Ti whereas the Implant B was made of Ti6Al4V alloy. Obtained results evidenced the common features and differences due to specific process parameters used in the treatments of mordanting and sandblasting for surface roughening. Implant A exhibits a uniform surface covered by very small dimples of about 1–2 μm. The surface of Implant B is not homogeneous: The thread tops present an irregular morphology (dimples size >10 μm) while finer dimples (about 1 μm) are observed along the thread flanks and valleys. Implant C shows an irregular morphology with dimples of different sizes and shapes distributed on thread tops, flanks, and valleys. XPS analyses revealed the presence of metal oxides: TiO2 in all the implants; Al2O3 and V2O5 only in the implant B. Moreover, these results demonstrated that Mg2SiO4 is present on the surface of Implant A, probably due to a specific preparation process. Obtained results have been discussed on the basis of the factors promoting the osseointegration.

The restrictions associated with the current SARS-Cov-2 pandemic are having a major impact on nearly all human activities and interactions; among these, the didactic and education field certainly has a prominent place. In the case of either complete lockdown or reduced accessibility to facilities and classrooms, the participation of students was severely limited for safety reasons. In particular, laboratory activities, already compromised by a large number of students of some classes, suffered from the restrictions, thus making it difficult to guarantee the possibility of live operating on instruments for the execution of measurements of different quantities of interest. To overcome the considered problem, this article proposes the use of enabling technologies of the Internet of Things and the fourth industrial revolution to allow students to achieve correct and complete training in laboratory activities. To this aim, remotely controlled instruments are used and displayed in augmented reality on consumer devices, such as mobile phones, tablets, or personal computers. The continuous availability of access to the instruments along with the realism in their representation and use ensures a positive and effective involvement of the students.

A three dimensional magnetic patterning of two cell types was realised in vitro inside an additive manufactured magnetic scaffold, as a conceptual precursor for the vascularised tissue. The realisation of separate arrangements of vascular and osteoprogenitor cells, labelled with biocompatible magnetic nanoparticles, was established on the opposite sides of the scaffold fibres under the effect of non-homogeneous magnetic gradients and loading magnetic configuration. The magnetisation of the scaffold amplified the guiding effects by an additional trapping of cells due to short range magnetic forces. The mathematical modelling confirmed the strong enhancement of the magnetic gradients and their particular geometrical distribution near the fibres, defining the preferential cell positioning on the micro-scale. The manipulation of cells inside suitably designed magnetic scaffolds represents a unique solution for the assembling of cellular constructs organised in biologically adequate arrangements.

Oxidized polyvinyl alcohol (OxPVA) is a new polymer for the fabrication of nerve conduits (NCs). Looking for OxPVA device optimization and coupling it with a natural sheath may boost bioactivity. Thus, OxPVA/chitosan sponges (ChS) as hybrid scaffolds were investigated to predict in the vivo behaviour of two-layered NCs. To encourage interaction with cells, ChS were functionalized with the self-assembling-peptide (SAP) EAK, without/with the laminin-derived sequences -IKVAV/-YIGSR. Thus, ChS and the hybrid scaffolds were characterized for mechanical properties, ultrastructure (Scanning Electron Microscopy, SEM), bioactivity, and biocompatibility. Regarding mechanical analysis, the peptide-free ChS showed the highest values of compressive modulus and maximum stress. However, among +EAK groups, ChS+EAK showed a significantly higher maximum stress than that found for ChS+EAK-IKVAV and ChS+EAK-YIGSR. Considering ultrastructure, microporous interconnections were tighter in both the OxPVA/ChS and +EAK groups than in the others; all the scaffolds induced SH-SY5Y cells’ adhesion/proliferation, with significant differences from day 7 and a higher total cell number for OxPVA/ChS+EAK scaffolds, in accordance with SEM. The scaffolds elicited only a slight inflammation after 14 days of subcutaneous implantation in Balb/c mice, proving biocompatibility. ChS porosity, EAK 3D features and neuro-friendly attitude (shared with IKVAV/YIGSR motifs) may confer to OxPVA certain bioactivity, laying the basis for future appealing NCs.

Titanium alloys (e.g., Ti6Al4V) have been widely considered for the design of biomedical implants. To avoid stress shielding effects, bone atrophy and implant loosening bone, 3D porous devices with controlled geometry and architecture should represent a promising solution. Several cellular structures were already investigated to obtain a wide range of mechanical properties. Many studies focused on the mechanical performance of diamond and body-centered-cubic. Different kinds of porous and semi-porous femoral stems were also proposed and analyzed. Accordingly, the aim of the current research was to provide further insight into the design of solid-lattice hybrid structures through a two-step process involving the classical and lattice topology optimization. A cementless femoral stem was considered as a case study. The solid isotropic material with penalization (SIMP) was used at varying values of the penalty factor and the effect of the geometrical features of each beam forming the lattice structure was also determined. Differences were found in terms of functional and structural performances according to the selected strategy for the design of the solid-lattice hybrid structures, as a consequence of the material distribution/layout and geometrical features.

Additive manufacturing (AM) allows the development of novel and customized products with tailored properties. However, the application of extrusion-based AM techniques (i.e., fused deposition modeling - FDM) in the design of functional parts is often limited because of the poor mechanical performance as a consequence of the nature of the process to build the object in a layer-by-layer fashion. In the current study, the impact resistance of the 3D printed polyethylene terephthalate glycol-modified (PETG) and high impact polystyrene (HIPS) was evaluated as a function of three printing parameters (i.e., printing temperature, layer height and line width). Izod-type test specimens were fabricated and analyzed according to the ASTM D256. The contribution of each factor was properly analyzed. The results also indicated that the printing temperature was the most significant parameter for the impact resistance of 3D printed PETG and HIPS. The obtained findings may be considered as valid only within the limit of parameters and ranges investigated in the current study.

The recent increase on the Internet of Things and Industry 4.0 fields has led the research topics to investigate on the innovative technologies that could support these emerging topics in different area of applications. In particular, the current trends are to close the gap between the physical and digital worlds, thus originating the so-called Cyber-Physical System (CPS). A relevant feature of the CPS is the digital twin, i.e., a digital replica of a process/product with which user can interact to operate on the real world. In this paper, the authors propose an innovative approach exploiting an Augmented Reality solution as Digital Twin for the measurement instrument to obtain a tight connection between the measurements as physical world and the Internet of Things as digital applications. In fact, by means of the adoption of the 3D scanning strategy, Augmented Reality software and with the development of a suitable connection between the instrument and the digital world, a Cyber-Physical System has been realized as an IoT platform that collect and control the real measurement instrument and makes its available in Augmented Reality. An application example involving a digital storage oscilloscope is finally presented to highlight the efficacy of the proposed approach.

Tissue engineering or tissue reconstruction/repair/regeneration may be considered as a guiding strategy in oral and maxillofacial surgery, as well as in endodontics, orthodontics, periodontics, and daily clinical practice. A wide range of techniques has been developed over the past years, from tissue grafts to the more recent and innovative regenerative procedures. Continuous research in the field of natural and artificial materials and biomaterials, as well as in advanced scaffold design strategies has been carried out. The focus has also been on various growth factors involved in dental tissue repair or reconstruction. Benefiting from the recent literature, this review paper illustrates current innovative strategies and technological approaches in oral and maxillofacial tissue engineering, trying to offer some information regarding the available scientific data and practical applications. After introducing tissue engineering aspects, an overview on additive manufacturing technologies will be provided, with a focus on the applications of superparamagnetic iron oxide nanoparticles in the biomedical field. The potential applications of magnetic fields and magnetic devices on the acceleration of orthodontic tooth movement will be analysed.

The limitations due to the SARS-Cov-2 pandemic affected both interactions between people and work activities; particularly in the educational field. In fact, the students were forced to face the lessons from home, which did not bring problems in the understanding of theoretical aspects, but turned out to be a problem regarding the laboratory activities, since they did not have the possibility to test on real instruments what they learned in theory. In this sense, this article describes the development of a remote laboratory in augmented reality, which allows instruments to be faithfully replicated on any portable device available to the students. Furthermore, by exploiting the protocols typical of the Internet of Things, it is possible to guarantee proper control of the real workstation by interacting with the one in augmented reality.

The advantages of additive manufactured scaffolds, as custom-shaped structures with a completely interconnected and accessible pore network from the micro- to the macroscale, are nowadays well established in tissue engineering. Pore volume and architecture can be designed in a controlled fashion, resulting in a modulation of scaffold’s mechanical properties and in an optimal nutrient perfusion determinant for cell survival. However, the success of an engineered tissue architecture is often linked to its surface properties as well. The aim of this study was to create a family of polymeric pastes comprised of poly(ethylene oxide therephthalate)/poly(butylene terephthalate) (PEOT/PBT) microspheres and of a second biocompatible polymeric phase acting as a binder. By combining microspheres with additive manufacturing technologies, we produced 3D scaffolds possessing a tailorable surface roughness, which resulted in improved cell adhesion and increased metabolic activity. Furthermore, these scaffolds may offer the potential to act as drug delivery systems to steer tissue regeneration.

The current research reports for the first time the use of blends of poly(e-caprolactone) (PCL) and poly(ester amide) (PEA) for the fabrication of 3D additive manufactured scaffolds. Tailor made PEA was synthesized to afford fully miscible blends of PCL and PEA using different percentages (5, 10, 15 and 20% w/w). Stability, characteristic temperatures and material's compatibility were studied through thermal analyses (i.e., TGA, DSC). Even though DMTA and static compression tests demonstrated the possibility to improve the storage modulus, Young's modulus and maximum stress by increasing the amount of PEA, a decrease of hardness was found beyond a threshold concentration of PEA as the lowest values were achieved for PCL/PEA (20% w/w) scaffolds (from 0.39 ± 0.03 GPa to 0.21 ± 0.02 GPa in the analysed load range). The scaffolds presented a controlled morphology and a fully interconnected network of internal channels. The water contact angle measurements showed a clear increase of hydrophilicity resulting from the addition of PEA. This result was further corroborated with the improved adhesion and proliferation of human mesenchymal stem cells (hMSCs). The presence of PEA also influenced the cell morphology. Better cell spreading and a much higher and homogenous number of cells were observed for PCL/PEA scaffolds when compared to PCL ones.

Background The combination of breast conserving surgery (BCS) with plastic surgery techniques has provided a useful surgical tool matching the radicality of the oncological excision with the preservation of breast cosmesis. Even though BCS represents a good option for surgical treatment of tumors located in these quadrants, wide excisions often necessitate breast reshaping in order to avoid nipple areola complex (NAC) displacement and skin retraction. We present a new surgical technique to repair upper-outer quadrants’ defects following breast cancer excision using dermo-glandular flaps and an axillary adipo-fascial flap. Methods During the period from January 2014 to December 2015, 168 patients with an upper-outer quadrant’s breast cancer have been treated in our Department. 83 women have been treated with the described oncoplastic technique and immediate contra-lateral symmetrisation and 85 women underwent standard BCS. We present surgical, oncological and cosmetic outcomes comparing our results with standard BCS. Results At a mean follow-up of 27 months loco-regional recurrences in the two groups were comparable. Short-term complication rates were comparable between the two groups. Re-intervention rates for positive margins were significantly higher in the standard BCS group. The overall satisfaction with cosmetic outcome both assessed by the patient and the surgeon was significantly higher in the oncoplastic group. Conclusions The proposed oncoplastic technique represents a safe and effective solution for reshaping that follows upper-outer breast cancer wide excision, achieving comparable complication rates, lower re-intervention rates for positive margins and better cosmetic results when compared with standard BCS.

Alzheimer's disease (AD), is the most common neurodegenerative disorder of the aging population resulting in progressive cognitive and functional decline. Accumulation of amyloid plaques around neuronal cells is considered a critical pathogenetic event and, in most cases, a hallmark of the pathology. In the attempt to identify anti-AD drug candidates, hundreds of molecules targeting Aβ peptides have been screened. Peptide molecules have been widely explored, appreciating chemical stability, biocompatibility, and low production cost. More recently, many anti-Aβ(1-42) monoclonal antibodies have been developed, given the excellent potential of immunotherapy for treating or preventing AD. Antibodies are versatile ligands that bind a large variety of molecules with high affinity and specificity; however, their extensive therapeutic application is complex and requires huge economic investments. Novel approaches to identify alternative antibody formats are considered with great interest. In this context, taking advantage of the favorable peptide properties and the availability of Aβ-antibodies structural data, we followed an innovative research approach to identify short peptide sequences on the model of the binding sites of Aβ(1-42)/antibodies. WAibH and SYSTPGK were designed as mimics of solanezumab and aducanumab, respectively. Circular dichroism and nuclear magnetic resonance analysis reveal that the antibody-derived peptides interact with Aβ(1-42) in the soluble monomeric form. Moreover, AFM microscopy imaging shows that WAibH and SYSTPGK are capable of controlling the Aβ(1-42) aggregation. The strategy to identify WAibH and SYSTPGK is innovative and can be widely applied for new anti-Aβ antibody mimicking peptides.

Growing numbers of asymptomatic women who become aware of carrying a breast cancer gene mutation (BRCA) mutation are choosing to undergo risk-reducing bilateral mastectomies with immediate breast reconstruction. We reviewed the literature with the aim of assessing the oncological safety of nipple-sparing mastectomy (NSM) as a risk-reduction procedure in BRCA-mutated patients. Nine studies reporting on the incidence of primary breast cancer post NSM in asymptomatic BRCA mutated patients undergoing risk-reducing bilateral procedures met the inclusion criteria. NSM appears to be a safe option for BRCA mutation carriers from an oncological point of view, with low reported rates of new breast cancers, low rates of postoperative complications, and high levels of satisfaction and postoperative quality of life. However, larger multi-institutional studies with longer follow-up are needed to establish this procedure as the best surgical option in this setting.

A wide range of materials has been considered to repair cranial defects. In the field of cranioplasty, poly(methyl methacrylate) (PMMA)-based bone cements and modifications through the inclusion of copper doped tricalcium phosphate (Cu-TCP) particles have been already investigated. On the other hand, aliphatic polyesters such as poly(&epsilon, caprolactone) (PCL) and polylactic acid (PLA) have been frequently investigated to make scaffolds for cranial bone regeneration. Accordingly, the aim of the current research was to design and fabricate customized hybrid devices for the repair of large cranial defects integrating the reverse engineering approach with additive manufacturing, The hybrid device consisted of a 3D additive manufactured polyester porous structures infiltrated with PMMA/Cu-TCP (97.5/2.5 w/w) bone cement. Temperature profiles were first evaluated for 3D hybrid devices (PCL/PMMA, PLA/PMMA, PCL/PMMA/Cu-TCP and PLA/PMMA/Cu-TCP). Peak temperatures recorded for hybrid PCL/PMMA and PCL/PMMA/Cu-TCP were significantly lower than those found for the PLA-based ones. Virtual and physical models of customized devices for large cranial defect were developed to assess the feasibility of the proposed technical solutions. A theoretical analysis was preliminarily performed on the entire head model trying to simulate severe impact conditions for people with the customized hybrid device (PCL/PMMA/Cu-TCP) (i.e., a rigid sphere impacting the implant region of the head). Results from finite element analysis (FEA) provided information on the different components of the model.

During anticancer drug development, most compounds selected by in vitro screening are ineffective in in vivo studies and clinical trials due to the unreliability of two-dimensional (2D) in vitro cultures that are unable to mimic the cancer microenvironment. Herein, HCC1954 cell cultures on electrospun polycaprolactone (PCL) were characterized by morphological analysis, cell viability assays, histochemical staining, immunofluorescence, and RT-PCR. Our data showed that electrospun PCL allows the in vitro formation of cultures characterized by mucopolysaccharide production and increased cancer stem cell population. Moreover, PCL-based cultures were less sensitive to doxorubicin and electroporation/bleomycin than those grown on polystyrene plates. Collectively, our data indicate that PCL-based cultures may be promising tools for preclinical studies.