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SSRN 2024年

作者： Trucco, Diego Gibney, Rory Vannozzi, Lorenzo Lisignoli, Gina Kelly, Daniel J. Ricotti, Leonardo The BioRobotics Institute Scuola Superiore Sant’Anna Piazza Martiri della Libertà 33 Pisa56127 Italy Department of Excellence in Robotics & AI Scuola Superiore Sant’Anna Piazza Martiri della Libertà 33 Pisa56127 Italy IRCCS Istituto Ortopedico Rizzoli SC Laboratorio di Immunoreumatologia e Rigenerazione Tissutale Via di Barbiano 1/10 Bologna40136 Italy Trinity Centre for Biomedical Engineering Trinity Biomedical Sciences Institute Trinity College Dublin Ireland Department of Mechanical Manufacturing and Biomedical Engineering School of Engineering Trinity College Dublin Ireland

Hydrogels are commonly used for tissue engineering applications due to their high water content, biocompatibility, injectability, and ability to mimic the extracellular matrix of native tissues. However, their weak mechanical properties limit their use, especially in load-bearing applications. In this study, we developed fibrous architectures with a pre-defined shape using melt electro-writing (MEW) to strengthen injectable hydrogels. We assessed the injection forces required to successfully extrude the hydrogel reinforced with MEW-printed structures, varying their geometry (square/hexagonal pores) and pore sizes (0.6, 0.8, 1.0 mm) through needles having a size compatible with clinical applications. Our findings indicate that MEW structures with hexagonal pores exhibit a higher tensile modulus than those with square pores. Additionally, the injection forces required to extrude hydrogels embedding MEW structures through needles were greater for hexagonal pores. Thinner pores and smaller needle diameters resulted in higher injection forces;a few conditions among the ones tested were compatible with the limits defined by the EU-ISO-7886-1:2018 standard. After injection and crosslinking, hydrogels reinforced with MEW structures showed improved mechanical properties (up to 6.34-fold), particularly when structures with hexagonal pores were used. © 2024, The Authors. All rights reserved.

关键词： Pore size

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Calibration of a biophysical model to replicate evoked compound action potentials in the swine vagus nerve

Calibration of a biophysical model to replicate evoked compo...

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Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)

作者： Claudio Verardo Ciro Zinno Simone Romeni Filippo Agnesi Fabio Bernini Anar Dushpanova Valentina Casieri Vincenzo Lionetti Silvestro Micera Department of Excellence in Robotics & AI The BioRobotics Institute Scuola Superiore Sant’Anna Pisa Italy Bertarelli Foundation Chair in Translational NeuroEngineering Neuro-X Institute EPFL Genève Switzerland BioMedLab Interdisciplinary Research Center “Health Science” Scuola Superiore Sant’Anna Pisa Italy Unit of Translational Critical Care Medicine Laboratory of Basic and Applied Medical Sciences Interdisciplinary Research Center “Health Science” Scuola Superiore Sant’Anna Pisa Italy Al-Farabi Kazakh National University Almaty Kazakhstan Fondazione Toscana "G. Monasterio" Pisa Italy

ISBN: (数字)9798350371499

ISBN: (纸本)9798350371505

Vagus nerve stimulation (VNS) is a promising application of bioelectronic medicine to treat many pathologies, ranging from epilepsy and depression to cardiovascular diseases. Conventional VNS is not optimized taking into account the topographic organization of the vagus nerve, resulting in suboptimal stimulation protocols, which can lead to severe adverse effects. The development of in vivo methods to determine topographic organization would allow more selective stimulation protocols and is thus pivotal in the development of future therapies. Here, we show that it may be possible to reverse-engineer vagus nerve topographic organization starting from experimental evoked compound action potentials (ECAPs). The parameters of a biophysical model of ECAP generation are varied until the optimal matching between synthetic and experimental ECAPs is determined. In the present work, we managed to match an experimental ECAP obtained from swine VNS, and to replicate the shape of an unseen experimental ECAP through the optimized parameters. This work paves the way to the automatic optimization of selective VNS protocols, opening to new important therapeutic opportunities.

关键词： In vivo Pathology Protocols Action potentials Shape Biological system modeling Organizations Recording Compounds Optimization

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Visible Light-Mediated Cross-Linking of Injectable Gellan Gum Hydrogels Embedding Human Chondrocytes

SSRN

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SSRN 2023年

作者： Trucco, Diego Vannozzi, Lorenzo Gabusi, Elena Lenzi, Enrico Manferdini, Cristina Bacci, Alessia Agresti, Liliana Pascale, Maria Rosaria Cristino, Sandra Lisignoli, Gina Ricotti, Leonardo The BioRobotics Institute Scuola Superiore Sant’Anna Piazza Martiri della Libertà 33 Pisa56127 Italy Department of Excellence in Robotics & AI Scuola Superiore Sant’Anna Piazza Martiri della Libertà 33 Pisa56127 Italy IRCCS Istituto Ortopedico Rizzoli SC Laboratorio di Immunoreumatologia e Rigenerazione Tissutale Via di Barbiano 1/10 Bologna40136 Italy Department of Biological Geological and Environmental Sciences University of Bologna via San Giacomo 12 Bologna40126 Italy

Gellan gum, a polysaccharide with structural similarities to glycosaminoglycans, is gaining attention in cartilage tissue engineering. It can be chemically modified with methacrylic moieties to produce a photocrosslinkable formulation, called methacrylated gellan gum (GGMA), envisaging the injection and the in situ cross-linking through light on the cartilage *** study aimed to investigate the visible light cross-linking of GGMA, underlying the impact of steam sterilization on its chemical and rheological properties and cross-linking efficiency. After an initial assessment of the sterilization effects, we evaluated a combination of hydrogel concentrations (1 and 2% w/v), ruthenium/sodium persulfate concentrations (0.1/1, 0.2/2 and 0.5/5 mM ratios), and light exposure times (30, 60 and, 120 s). The formulations with the lowest sol fraction were characterized for mechanical and showed self-healing properties. Biological characterization on encapsulated chondrocytes in hydrogels showed high cell viability with increased metabolic activity over two weeks. The expression of genes encoding collagen type II and cartilage oligomeric matrix protein was upregulated in the softer formulation (E=0.95±0.48 kPa) composed of 2% w/v GGMA, 0.1/1 mM Ru/SPS, and photo-crosslinked for 60 s. These findings represent an interesting overview of the potential application of visible-light crosslinked GGMA in the clinical scenario to treat cartilage defects. © 2023, The Authors. All rights reserved.

关键词： Hydrogels

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3D bioprinting of thermosensitive inks based on gelatin, hyaluronic acid, and fibrinogen: reproducibility and role of printing parameters

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Bioprinting 2024年 39卷

作者： Iberite, Federica Badiola-Mateos, Maider Loggini, Sara Paci, Claudia Ruspi, Jacopo Iachetta, Daniele Mannini, Andrea Gruppioni, Emanuele Ricotti, Leonardo The BioRobotics Institute Scuola Superiore Sant'Anna Piazza Martiri della Libertà 33 Pisa 56127 Italy Department of Excellence in Robotics & AI Scuola Superiore Sant'Anna Piazza Martiri della Libertà 33 Pisa 56127 Italy IRCCS Fondazione Don Carlo Gnocchi ONLUS Florence Italy Centro Protesi INAIL Istituto Nazionale per l'Assicurazione contro gli Infortuni sul Lavoro Vigorso di Budrio Bologna 40054 Italy

Thermosensitive inks are considered an attractive option for the 3D bioprinting of different tissue types, yet comprehensive information on their reliability, preparation, and properties remains lacking. This paper addresses this gap by presenting a twofold aim: firstly, characterizing the preparation, rheology, and printing aspects of two inks that have demonstrated success in skeletal muscle tissue engineering both in vitro and in vivo. The first ink is composed of fibrinogen, gelatin, hyaluronic acid, and glycerol, while the second is a sacrificial ink made of gelatin, hyaluronic acid, and glycerol. Secondly, from this analysis, we demonstrate how thermosensitive and multicomponent inks can exhibit high variability and unpredictability. Thus, we emphasize the importance of thorough ink characterization to ensure the reproducibility and reliability of scientific outcomes. We quantified the inherent variability in ink manufacturing and we proposed specific quality assessment criteria. We found storing the fibroink at 4 °C for one day did not alter fibroink properties, while significant changes were produced if the storage time was seven days. Cell viability within the fibroink was evaluated at different temperatures, identifying 9 °C as the optimal trade-off between cell viability and printability. Rheological analyses confirmed the shear-thinning behavior of both inks and identified their respective sol-gel transition temperatures. A systematic assessment of printing fidelity was performed, by varying pressure, speed, and needle offset. The methodology proposed in this study may be useful for the management of other thermosensitive bioinks, thus properly considering their inherent variability. © 2024 The Authors

关键词： 3D bioprinting Extrusion-based bioprinting Fibrin Printability Rheology Thermosensitive bioink

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Real-time human pose estimation on a smart walker using convolutional neural networks

arXiv

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arXiv 2021年

作者： Palermo, Manuel Moccia, Sara Migliorelli, Lucia Frontoni, Emanuele Santos, Cristina P. Center for Microelectromechanical Systems University of Minho Portugal The BioRobotics Institute Scuola Superiore Sant’Anna Pisa Italy Department of Excellence in Robotics and AI Scuola Superiore Sant’Anna Pisa Italy Politecnica delle Marche Ancona Italy

Rehabilitation is important to improve quality of life for mobility-impaired patients. Smart walkers are a commonly used solution that should embed automatic and objective tools for data-driven human-in-the-loop control and monitoring. However, present solutions focus on extracting few specific metrics from dedicated sensors with no unified full-body approach. We investigate a general, real-time, full-body pose estimation framework based on two RGB+D camera streams with non-overlapping views mounted on a smart walker equipment used in rehabilitation. Human keypoint estimation is performed using a two-stage neural network framework. The 2D-Stage implements a detection module that locates body keypoints in the 2D image frames. The 3D-Stage implements a regression module that lifts and relates the detected keypoints in both cameras to the 3D space relative to the walker. Model predictions are low-pass filtered to improve temporal consistency. A custom acquisition method was used to obtain a dataset, with 14 healthy subjects, used for training and evaluating the proposed framework offline, which was then deployed on the real walker equipment. An overall keypoint detection error of 3.73 pixels for the 2D-Stage and 44.05mm for the 3D-Stage were reported, with an inference time of 26.6ms when deployed on the constrained hardware of the walker. We present a novel approach to patient monitoring and data-driven human-in-the-loop control in the context of smart walkers. It is able to extract a complete and compact body representation in real-time and from inexpensive sensors, serving as a common base for downstream metrics extraction solutions, and Human-Robot interaction applications. Despite promising results, more data should be collected on users with impairments, to assess its performance as a rehabilitation tool in real-world scenarios. © 2021, CC BY-NC-ND.

关键词： Patient rehabilitation

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Online Estimation of Continuous Gait Phase for Robotic Transtibial Prostheses Based on Adaptive Oscillators

Online Estimation of Continuous Gait Phase for Robotic Trans...

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IEEE/ASME (aiM) International Conference on Advanced Intelligent Mechatronics

作者： Dongfang Xu Simona Crea Nicola Vitiello Qining Wang Department of Advanced Manufacturing and Robotics Peking University Beijing China BioRobotics Institute and Department of Excellence in Robotics & AI Scuola Superiore Sant’Anna Pisa Italy

ISBN: (数字)9781728167947

ISBN: (纸本)9781728167954

Continuous gait phase plays an important role in wearable robot control. This study focuses on the online estimation of continuous gait phase based on robotic transtibial prosthesis signals. First, we adopt the prosthetic foot deformation information to detect the heel strike as the start timing (reset 0 rad) of one gait cycle. Then we conduct the gait phase estimation based on adaptive oscillators using the prosthetic shank angle signal as input. Three transtibial amputees were recruited in this study and they walked on the treadmill at different speeds (slow, normal and fast) and on different ramps (10°, 5°, 0°, -5° and -10°) in the experiment. The root-mean-square error between online estimation result and ground truth gait phase is calculated. The maximum and minimum errors are 0.147 rad and 0.058 rad, and the corresponding ratios in one gait cycle are 2.34% and 0.92%. This study achieves good performance and provides an effective method to estimate the continuous gait phase, which will instruct robotic transtibial prosthesis control.

关键词： Prosthetics Phase estimation Foot Estimation Oscillators Legged locomotion

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Visible Light-Mediated Cross-Linking of Injectable Gellan Gum Hydrogels Embedding Human Chondrocytes

SSRN

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SSRN 2023年

Gellan gum, a polysaccharide with structural similarities to glycosaminoglycans, is gaining attention in cartilage tissue engineering. It can be chemically modified with methacrylic moieties to produce a photocrosslinkable formulation, called methacrylated gellan gum (GGMA), envisaging the injection and the in situ cross-linking through light on the cartilage surface. This study aimed to investigate the visible light cross-linking of GGMA, underlying the impact of steam sterilization on its chemical and rheological properties and cross-linking efficiency. After an initial assessment of the sterilization effects, we evaluated a combination of hydrogel concentrations (1 and 2% w/v), ruthenium/sodium persulfate concentrations (0.1/1, 0.2/2 and 0.5/5 mM ratios), and light exposure times (30, 60 and, 120 s). The formulations with the lowest sol fraction were characterized for mechanical and showed self-healing properties. Biological characterization on encapsulated chondrocytes in hydrogels showed high cell viability with increased metabolic activity over two weeks. The expression of genes encoding collagen type II and cartilage oligomeric matrix protein was upregulated in the softer formulation (E=0.95±0.48 kPa) composed of 2% w/v GGMA, 0.1/1 mM Ru/SPS, and photo-crosslinked for 60 s. These findings represent an interesting overview of the potential application of visible-light crosslinked GGMA in the clinical scenario to treat cartilage defects. © 2023, The Authors. All rights reserved.

关键词： Hydrogels

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Design of magnetic coupling-based anti-biofouling mechanism for underwater optical sensors

arXiv

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arXiv 2022年

作者： Ramirez, Jane Pauline Stefanini, Cesare De Masi, Giulia Romano, Donato The BioRobotics Institute Sant’Anna School of Advanced Studies Viale Rinaldo Piaggio 34 Pisa Pontedera56025 Italy Department of Excellence in Robotics and AI Sant’Anna School of Advanced Studies Pisa56127 Italy Healthcare Engineering Innovation Center Khalifa University Abu Dhabi United Arab Emirates Autonomous and Robotics Research Centre Technology Innovation Institute Abu Dhabi United Arab Emirates College of Engineering Khalifa University Abu Dhabi United Arab Emirates

Water monitoring is crucial for environmental monitoring, transportation, energy and telecommunication. One of the main problems in aquatic environmental monitoring is biofouling. The simplest method among the current antifouling strategies is the use of wiper technologies like brushes and wipers which apply mechanical pressure. In designing built-in strategies however, manufacturers usually build the sensor around the biofouling system. The current state-of-the-art is a fully integrated central wiper in the sensor that enables cleaning of all probes mounted on the sonde. Improvements in antifouling strategies lag rapid advancements in sensor technologies such as in miniaturization, specialization, and costs. Hence, improving built-in designs by decreasing size and complexity will decrease maintenance and overall costs. This design is targeted for the EU project Robocoenosis since bio-hybrid systems in this project incorporate living organisms. This technology targets selective proliferation of the organisms which only prevents biofilms on components where they are unwanted. Beyond this, the use of autonomous activation based on image processing may likely be advantageous for minimizing the need for human inspection and maintenance. In addition to Robocoenosis, we also aim at incorporating this design in another project entitled Heterogeneous Swarm of Underwater Autonomous Vehicles where a swarm of heterogeneous underwater robotic fish is being developed. © 2022, CC BY.

关键词： Image processing

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Patterns of neural activity and clinical outcomes in a juvenile Huntington's Disease patient undergoing Deep Brain Stimulation of the subthalamic nucleus

Deep Brain Stimulation

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Deep Brain Stimulation 2023年 1卷 15-19页

作者： Ahmet Kaymak Matteo Vissani Matteo Lenge Federico Melani Edoardo Fino Pietro Cappelletto Germana Tuccinardi Michele Alessandro Cavallo Flavio Giordano Alberto Mazzoni The Biorobotics Institute Scuola Superiore Sant’Anna Pisa Italy Department of Excellence for Robotics and AI Scuola Superiore Sant’Anna Pisa Italy Department of Neurosurgery Massachusetts General Hospital Boston United States of America Harvard Medical School Boston United States of America Department of Neurosurgery Meyer Children’s Hospital IRCSS Florence Italy Department of Neuroscience Meyer Children’s Hospital IRCSS Florence Italy Department of Neuroanesthesiology and Intensive Care Unit Meyer Children’s Hospital IRCSS Florence Italy Department of Neurosurgery University Hospital S. Anna University of Ferrara Ferrara Italy Neurofarba Department University of Florence Florence Italy

Background Huntington's disease (HD) is a hereditary neurodegenerative disease leading to cognitive and motor impairment. HD depends on basal ganglia dysfunctions, but the role of subthalamic nucleus (STN) neurons is not completely known. Drug-resistant motor symptoms of HD can be alleviated by neuromodulation of the basal ganglia through Deep Brain Stimulation (DBS) of STN. DBS target selection is supported by intra-operative microelectrode recordings (MER). MER have been previously used to characterize neural dynamics of STN in several movement disorders and can provide information on firing patterns underlying HD. Methods We analyzed MER data acquired during bilateral DBS of STN in a juvenile HD female patient with hypokinetic motor symptoms (generalized dystonia, stiffness, and severe gait impairment). Firing patterns of STN in HD were characterized by isolating single neuron activities (n = 23) and measuring their regularity, bursting, and oscillatory behavior. Multi-unit activity recordings spectrum was used to estimate the presence of network oscillations. Results STN neurons displayed irregular dynamics and intense and sparse bursting. Only 3/23 neurons presented oscillatory activity. However, network oscillations were detected, in particular in the beta (12–30 Hz) band. After bilateral STN-DBS surgery, the Unified Huntington's Disease Rating Scale decreased from 60 to 54. Conclusions The most salient difference between HD and other movement disorders in STN activity is the presence of a weakly synchronized oscillatory mode, in which oscillations are evident at the network level but not at the single neuron level.

关键词： Deep Brain Stimulation (DBS) Movement disorder Juvenile Huntington’s Disease Single Unit Activity Subthalamic nucleus (STN)

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A Federated Learning Framework for Stenosis Detection

arXiv

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arXiv 2023年

作者： Di Cosmo, Mariachiara Migliorelli, Giovanna Francioni, Matteo Muçaj, Andi Maolo, Alessandro Aprile, Alessandro Frontoni, Emanuele Fiorentino, Maria Chiara Moccia, Sara Department of Information Engineering Università Politecnica delle Marche Ancona Italy Department of Law Università degli Studi di Macerata Macerata Italy U.O.C. Cardiology and Hemodynamics Department of Cardiovascular Sciences Azienda Ospedaliero Universitaria delle Marche Ancona Italy U.O.C. Cardiology UTIC-Hemodynamics Ospedale del Mare ASL NA 1 Napoli Italy Department of Political Sciences Communication and International Relations University of Macerata Macerata Italy The BioRobotics Institute Department of Excellence in Robotics and AI Scuola Superiore Sant’Anna Pisa Italy

This study explores the use of Federated Learning (FL) for stenosis detection in coronary angiography images (CA). Two heterogeneous datasets from two institutions were considered: Dataset 1 includes 1219 images from 200 patients, which we acquired at the Ospedale Riuniti of Ancona (Italy);Dataset 2 includes 7492 sequential images from 90 patients from a previous study available in the literature. Stenosis detection was performed by using a Faster R-CNN model. In our FL framework, only the weights of the model backbone were shared among the two client institutions, using Federated Averaging (FedAvg) for weight aggregation. We assessed the performance of stenosis detection using Precision (Prec), Recall (Rec), and F1 score (F1). Our results showed that the FL framework does not substantially affects clients 2 performance, which already achieved good performance with local training;for client 1, instead, FL framework increases the performance with respect to local model of +3.76%, +17.21% and +10.80%, respectively, reaching Prec = 73.56, Rec = 67.01 and F1 = 70.13. With such results, we showed that FL may enable multicentric studies relevant to automatic stenosis detection in CA by addressing data heterogeneity from various institutions, while preserving patient privacy. © 2023, CC BY-NC-SA.

关键词： Computer aided instruction

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