Surgical Medical Education via 3D Bioprinting: Modular System for Endovascular Training.

There is currently a shift in surgical training from traditional methods to simulation-based approaches, recognizing the necessity of more effective and controlled learning environments. This study introduces a completely new 3D-printed modular system for endovascular surgery training (M-SET), developed to allow various difficulty levels. Its design was based on computed tomography angiographies from real patient data with femoro-popliteal lesions. The study aimed to explore the integration of simulation training via a 3D model into the surgical training curriculum and its effect on their performance. Our preliminary study included 12 volunteer trainees randomized 1:1 into the standard simulation (SS) group (3 stepwise difficulty training sessions) and the random simulation (RS) group (random difficulty of the M-SET). A senior surgeon evaluated and timed the final training session. Feedback reports were assessed through the Student Satisfaction and Self-Confidence in Learning Scale. The SS group completed the training sessions in about half time (23.13 ± 9.2 min vs. 44.6 ± 12.8 min). Trainees expressed high satisfaction with the training program supported by the M-SET. Our 3D-printed modular training model meets the current need for new endovascular training approaches, offering a customizable, accessible, and effective simulation-based educational program with the aim of reducing the time required to reach a high level of practical skills.

The Upper Limb Orthosis in the Rehabilitation of Stroke Patients: The Role of 3D Printing.

Stroke represents the third cause of long-term disability in the world. About 80% of stroke patients have an impairment of bio-motor functions and over half fail to regain arm functionality, resulting in motor movement control disorder with serious loss in terms of social independence. Therefore, rehabilitation plays a key role in the reduction of patient disabilities, and 3D printing (3DP) has showed interesting improvements in related fields, thanks to the possibility to produce customized, eco-sustainable and cost-effective orthoses. This study investigated the clinical use of 3DP orthosis in rehabilitation compared to the traditional ones, focusing on the correlation between 3DP technology, therapy and outcomes. We screened 138 articles from PubMed, Scopus and Web of Science, selecting the 10 articles fulfilling the inclusion criteria, which were subsequently examined for the systematic review. The results showed that 3DP provides substantial advantages in terms of upper limb orthosis designed on the patient's needs. Moreover, seven research activities used biodegradable/recyclable materials, underlining the great potential of validated 3DP solutions in a clinical rehabilitation setting. The aim of this study was to highlight how 3DP could overcome the limitations of standard medical devices in order to support clinicians, bioengineers and innovation managers during the implementation of Healthcare 4.0.

Three-Dimensional Bioprinting of Organoid-Based Scaffolds (OBST) for Long-Term Nanoparticle Toxicology Investigation.

The toxicity of nanoparticles absorbed through contact or inhalation is one of the major concerns for public health. It is mandatory to continually evaluate the toxicity of nanomaterials. In vitro nanotoxicological studies are conventionally limited by the two dimensions. Although 3D bioprinting has been recently adopted for three-dimensional culture in the context of drug release and tissue regeneration, little is known regarding its use for nanotoxicology investigation. Therefore, aiming to simulate the exposure of lung cells to nanoparticles, we developed organoid-based scaffolds for long-term studies in immortalized cell lines. We printed the viscous cell-laden material via a customized 3D bioprinter and subsequently exposed the scaffold to either 40 nm latex-fluorescent or 11-14 nm silver nanoparticles. The number of cells significantly increased on the 14th day in the 3D environment, from 5 × 105 to 1.27 × 106, showing a 91% lipid peroxidation reduction over time and minimal cell death observed throughout 21 days. Administered fluorescent nanoparticles can diffuse throughout the 3D-printed scaffolds while this was not the case for the unprinted ones. A significant increment in cell viability from 3D vs. 2D cultures exposed to silver nanoparticles has been demonstrated. This shows toxicology responses that recapitulate in vivo experiments, such as inhaled silver nanoparticles. The results open a new perspective in 3D protocols for nanotoxicology investigation supporting 3Rs.

Age-related increases in cardiac excitability, refractoriness and impulse conduction favor arrhythmogenesis in male rats.

The effects of excitability, refractoriness, and impulse conduction have been independently related to enhanced arrhythmias in the aged myocardium in experimental and clinical studies. However, their combined arrhythmic effects in the elderly are not yet completely understood. Hence, the aim of the present work is to relate relevant cardiac electrophysiological parameters to enhanced arrhythmia vulnerability in the in vivo senescent heart. We used multiple-lead epicardial potential mapping in control (9-month-old) and aged (24-month-old) rat hearts. Cardiac excitability and refractoriness were evaluated at numerous epicardial test sites by means of the strength-duration curve and effective refractory period, respectively. During sinus rhythm, durations of electrogram intervals and waves were prolonged in the senescent heart, compared with control, demonstrating a latency in tissue activation and recovery. During ventricular pacing, cardiac excitability, effective refractory period, and dispersion of refractoriness increased in the aged animal. This scenario was accompanied by impairment of impulse propagation. Moreover, both spontaneous and induced arrhythmias were increased in senescent cardiac tissue. Histopathological evaluation of aged heart specimens revealed connective tissue deposition and perinuclear myocytolysis in the atria, while scattered microfoci of interstitial fibrosis were mostly present in the ventricular subendocardium. This work suggests that enhanced arrhythmogenesis in the elderly is a multifactorial process due to the joint increase in excitability and dispersion of refractoriness in association with enhanced conduction inhomogeneity. The knowledge of these electrophysiological changes will possibly contribute to improved prevention of the age-associated increase in cardiac arrhythmias.

Immersive Virtual Reality in Post-Stroke Rehabilitation: A Systematic Review.

In recent years, next to conventional rehabilitation's techniques, new technologies have been applied in stroke rehabilitation. In this context, fully immersive virtual reality (FIVR) has showed interesting results thanks to the level of immersion of the subject in the illusional world, with the feeling of being a real part of the virtual environment. This study aims to investigate the efficacy of FIVR in stroke rehabilitation. PubMed, Web of Science and Scopus were screened up to November 2022 to identify eligible randomized controlled trials (RCTs). Out of 4623, we included 12 RCTs involving post-acute and chronic stroke survivors, with a total of 350 patients (234 men and 115 women; mean age 58.36 years). High heterogeneity of the outcomes considered, the results showed that FIVR provides additional benefits, in comparison with standard rehabilitation. In particular, results showed an improvement in upper limb dexterity, gait performance and dynamic balance, influencing patient independence. Therefore, FIVR represents an adaptable, multi-faceted rehabilitation tool that can be considered in post-stroke rehabilitation, improving the compliance of the patients to the treatment and increasing the level of functioning and quality of life of stroke survivors.

Gait Alteration in Individual with Limb Loss: The Role of Inertial Sensors.

Amputation has a big impact on the functioning of patients, with negative effects on locomotion and dexterity. In this context, inertial measurement units represent a useful tool in clinical practice for motion analysis, and in the development of personalized aids to improve a patient's function. To date, there is still a gap of knowledge in the scientific literature on the application of inertial sensors in amputee patients. Thus, the aim of this narrative review was to collect the current knowledge on this topic and stimulate the publication of further research. Pubmed, Embase, Scopus, and Cochrane Library publications were screened until November 2022 to identify eligible studies. Out of 444 results, we selected 26 articles focused on movement analysis, risk of falls, energy expenditure, and the development of sensor-integrated prostheses. The results showed that the use of inertial sensors has the potential to improve the quality of life of patients with prostheses, increasing patient safety through the detection of gait alteration; enhancing the socio-occupational reintegration through the development of highly technologic and personalized prosthesis; and by monitoring the patients during daily life to plan a tailored rehabilitation program.

Artificial Intelligence Supports Decision Making during Open-Chest Surgery of Rare Congenital Heart Defects.

The human right ventricle is barely monitored during open-chest surgery due to the absence of intraoperative imaging techniques capable of elaborating its complex function. Accordingly, artificial intelligence could not be adopted for this specific task. We recently proposed a video-based approach for the real-time evaluation of the epicardial kinematics to support medical decisions. Here, we employed two supervised machine learning algorithms based on our technique to predict the patients' outcomes before chest closure. Videos of the beating hearts were acquired before and after pulmonary valve replacement in twelve Tetralogy of Fallot patients and recordings were properly labeled as the "unhealthy" and "healthy" classes. We extracted frequency-domain-related features to train different supervised machine learning models and selected their best characteristics via 10-fold cross-validation and optimization processes. Decision surfaces were built to classify two additional patients having good and unfavorable clinical outcomes. The k-nearest neighbors and support vector machine showed the highest prediction accuracy; the patients' class was identified with a true positive rate ≥95% and the decision surfaces correctly classified the additional patients in the "healthy" (good outcome) or "unhealthy" (unfavorable outcome) classes. We demonstrated that classifiers employed with our video-based technique may aid cardiac surgeons in decision making before chest closure.

3D Printed Masks for Powders and Viruses Safety Protection Using Food Grade Polymers: Empirical Tests.

The production of 3D printed safety protection devices (SPD) requires particular attention to the material selection and to the evaluation of mechanical resistance, biological safety and surface roughness related to the accumulation of bacteria and viruses. We explored the possibility to adopt additive manufacturing technologies for the production of respirator masks, responding to the sudden demand of SPDs caused by the emergency scenario of the pandemic spread of SARS-COV-2. In this study, we developed different prototypes of masks, exclusively applying basic additive manufacturing technologies like fused deposition modeling (FDM) and droplet-based precision extrusion deposition (db-PED) to common food packaging materials. We analyzed the resulting mechanical characteristics, biological safety (cell adhesion and viability), surface roughness and resistance to dissolution, before and after the cleaning and disinfection phases. We showed that masks 3D printed with home-grade printing equipment have similar performances compared to the industrial-grade ones, and furthermore we obtained a perfect face fit by customizing their shape. Finally, we developed novel approaches to the additive manufacturing post-processing phases essential to assure human safety in the production of 3D printed custom medical devices.

Bionic for Training: Smart Framework Design for Multisensor Mechatronic Platform Validation.

Home monitoring supports the continuous improvement of the therapy by sharing data with healthcare professionals. It is required when life-threatening events can still occur after hospital discharge such as neonatal apnea. However, multiple sources of external noise could affect data quality and/or increase the misdetection rate. In this study, we developed a mechatronic platform for sensor characterizations and a framework to manage data in the context of neonatal apnea. The platform can simulate the movement of the abdomen in different plausible newborn positions by merging data acquired simultaneously from three-axis accelerometers and infrared sensors. We simulated nine apnea conditions combining three different linear displacements and body postures in the presence of self-generated external noise, showing how it is possible to reduce errors near to zero in phenomena detection. Finally, the development of a smart 8Ws-based software and a customizable mobile application were proposed to facilitate data management and interpretation, classifying the alerts to guarantee the correct information sharing without specialized skills.

Author Correction: In-vivo vascular application via ultra-fast bioprinting for future 5D personalised nanomedicine.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Alginate Formulations: Current Developments in the Race for Hydrogel-Based Cardiac Regeneration.

Cardiovascular diseases, including myocardial infarction (MI), represent the main worldwide cause of mortality and morbidity. In this scenario, to contrast the irreversible damages following MI, cardiac regeneration has emerged as a novel and promising solution for in situ cellular regeneration, preserving cell behavior and tissue cytoarchitecture. Among the huge variety of natural, synthetic, and hybrid compounds used for tissue regeneration, alginate emerged as a good candidate for cellular preservation and delivery, becoming one of the first biomaterial tested in pre-clinical research and clinical trials concerning cardiovascular diseases. Although promising results have been obtained, recellularization and revascularization of the infarcted area present still major limitations. Therefore, the demand is rising for alginate functionalization and its combination with molecules, factors, and drugs capable to boost the regenerative potential of the cardiac tissue. The focus of this review is to elucidate the promising properties of alginate and to highlight its benefits in clinical trials in relation to cardiac regeneration. The definition of hydrogels, the alginate characteristics, and recent biomedical applications are herewith described. Afterward, the review examines in depth the ongoing developments to refine the material relevance in cardiac recovery and regeneration after MI and presents current clinical trials based on alginate.

In-vivo vascular application via ultra-fast bioprinting for future 5D personalised nanomedicine.

The design of 3D complex structures enables new correlation studies between the engineering parameters and the biological activity. Moreover, additive manufacturing technology could revolutionise the personalised medical pre-operative management due to its possibility to interplay with computer tomography. Here we present a method based on rapid freeze prototyping (RFP) 3D printer, reconstruction cutting, nano dry formulation, fast freeze gelation, disinfection and partial processes for the 5D digital models functionalisation. We elaborated the high-resolution computer tomography scan derived from a complex human peripheral artery and we reconstructed the 3D model of the vessel in order to obtain and verify the additive manufacturing processes. Then, based on the drug-eluting balloon selected for the percutaneous intervention, we reconstructed the biocompatible eluting-freeform coating containing 40 nm fluorescent nanoparticles (NPs) by means of RFP printer and we tested the in-vivo feasibility. We introduced the NPs-loaded 5D device in a rat's vena cava. The coating dissolved in a few minutes releasing NPs which were rapidly absorbed in vascular smooth muscle cell (VSMC) and human umbilical vein endothelial cell (HUVEC) in-vitro. We developed 5D high-resolution self-dissolving devices incorporating NPs with the perspective to apply this method to the personalised medicine.

Highly defined 3D printed chitosan scaffolds featuring improved cell growth.

The augmented demand for medical devices devoted to tissue regeneration and possessing a controlled micro-architecture means there is a need for industrial scale-up in the production of hydrogels. A new 3D printing technique was applied to the automation of a freeze-gelation method for the preparation of chitosan scaffolds with controlled porosity. For this aim, a dedicated 3D printer was built in-house: a preliminary effort has been necessary to explore the printing parameter space to optimize the printing results in terms of geometry, tolerances and mechanical properties of the product. Analysed parameters included viscosity of the starting chitosan solution, which was measured with a Brookfield viscometer, and temperature of deposition, which was determined by filming the process with a cryocooled sensor thermal camera. Optimized parameters were applied to the production of scaffolds from solutions of chitosan alone or with the addition of raffinose as a viscosity modifier. Resulting hydrogels were characterized in terms of morphology and porosity. In vitro cell culture studies comparing 3D printed scaffolds with their homologous produced by solution casting evidenced an improvement in biocompatibility deriving from the production technique as well as from the solid state modification of chitosan stemming from the addition of the viscosity modifier.

3D-printed polylactic acid supports for enhanced ionization efficiency in desorption electrospray mass spectrometry analysis of liquid and gel samples.

The potential of 3D printing technology was here exploited to prepare tailored polylactic acid (PLA) supports for desorption electrospray ionization (DESI) experiments. PLA rough solid supports presenting wells of different shape (i.e. cylindrical, cubic and hemispherical cavities) were designed to accommodate samples of different physical state. The potentials of such supports in terms of sample loading capacity, sensitivity, signal stability were tested by analysing a peptide (i.e. insulin) and an aminoglycoside antibiotic (i.e. gentamicin sulphate) from solution and a chitosan-based gel. The results obtained were compared with those obtained by using a traditional polytetrafluoroethylene (PTFE) support and discussed. By using PLA support on the flat side, signal intensity improved almost twice with respect to PTFE support, whereas with spherical wells a five times improved signal sensitivity and good stability (RSD<6%) were obtained for the analysis of two model molecules. Limits of detection were in the 3-10nM range and linearity was demonstrated for both analytes in the 0.05-0.5µM range for semi-quantitative or quantitative purposes. The use of a well and the set-up of optimal source parameters allowed the analysis of samples in a gel state with good precision (RSD<10%) and accuracy (86±6-102±9%), otherwise difficult to analyse on a flat smooth surface. These findings are of great interest and stimulus to exploit the advantages of 3D printing technology for the development of devices for a DESI source, presenting different shapes or configuration as a function of the sample types.