Fibronectin-Enriched Biomaterials, Biofunctionalization, and Proactivity: A Review

Modern innovation in reconstructive medicine implies the proposition of material-based strategies suitable for tissue repair and regeneration. The development of such systems necessitates the design of advanced materials and the control of their interactions with their surrounding cellular and molecular microenvironments. Biomaterials must actively engage cellular matter to direct and modulate biological responses at implant sites and beyond. Indeed, it is essential that a true dialogue exists between the implanted device and the cells. Biomaterial engineering implies the knowledge and control of cell fate considering the globality of the adhesion process, from initial cell attachment to differentiation. The extracellular matrix (ECM) represents a complex microenvironment able to meet these essential needs to establish a relationship between the material and the contacting cells. The ECM exhibits specific physical, chemical, and biochemical characteristics. Considering the complexity, heterogeneity, and versatility of ECM actors, fibronectin (Fn) has emerged among the ECM protagonists as the most pertinent representative key actor. The following review focuses on and synthesizes the research supporting the potential to use Fn in biomaterial functionalization to mimic the ECM and enhance cell–material interactions.

Neuromodulation for Refractory Epilepsy

Three neuromodulation therapies, all using implanted device and electrodes, have been approved to treat adults with drug-resistant focal epilepsy, namely, the vagus nerve stimulation in 1995, deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) in 2018 (2010 in Europe), and responsive neurostimulation (RNS) in 2014. Indications for VNS have more recently extended to children down to age of 4. Limited or anecdotal data are available in other epilepsy syndromes and refractory/super-refractory status epilepticus. Overall, neuromodulation therapies are palliative, with only a minority of patients achieving long-term seizure freedom, justifying favoring such treatments in patients who are not good candidates for curative epilepsy surgery. About half of patients implanted with VNS, ANT-DBS, and RNS have 50% or greater reduction in seizures, with long-term data suggesting increased efficacy over time. Besides their impact on seizure frequency, neuromodulation therapies are associated with various benefits and drawbacks in comparison to antiseizure drugs. Yet, we lack high-level evidence to best position each neuromodulation therapy in the treatment pathways of persons with difficult-to-treat epilepsy.

Clinical Impact of Preprocedural CT-Based 3D Computational Simulation of Left Atrial Appendage Occlusion with Amulet

Aims. Standard of care (SoC) device size selection with transoesophageal echocardiography (TOE) and computed tomography (CT) in LAAO can be challenging due to a certain degree of variability at both patient and device levels. The aim of this study was to prospectively evaluate the clinical impact of 3D computational modelling software in the decision-making of left atrial appendage occlusion (LAAO) with Amplatzer Amulet. Methods and Results. SoC preprocedural assessments as well as CT-based 3D computational simulations (FEops) were performed in 15 consecutive patients scheduled for LAAO with Amulet. Preprocedural device size selection and degree of confidence were determined after SoC and after FEops-based assessments and compared to the implanted device. FEops-based preprocedural assessment correctly selected the implanted device size in 11 out of 15 patients (73.3%), compared to 7 patients (46.7%) for SoC-based assessment. In 4 patients (26.7%), FEops induced a change in device size initially selected by SoC. In the 7 patients (46.7%) in which FEops confirmed the SoC device size selection, the degree of confidence of the size selection increased from 6.4 ± 1.4 for SoC to 8.1 ± 0.7 for FEops. One patient (6.7%) could not be implanted for anatomical reason, as correctly identified by FEops. Conclusions. Preprocedural 3D computational simulation by FEops impacts Amulet size selection in LAAO compared to TOE and CT-based SoC assessment. Operators could consider FEops computational simulation in their preprocedural device size selection.

Automated Localization of Focal Ventricular Tachycardia From Simulated Implanted Device Electrograms: A Combined Physics–AI Approach

Background: Focal ventricular tachycardia (VT) is a life-threating arrhythmia, responsible for high morbidity rates and sudden cardiac death (SCD). Radiofrequency ablation is the only curative therapy against incessant VT; however, its success is dependent on accurate localization of its source, which is highly invasive and time-consuming.Objective: The goal of our study is, as a proof of concept, to demonstrate the possibility of utilizing electrogram (EGM) recordings from cardiac implantable electronic devices (CIEDs). To achieve this, we utilize fast and accurate whole torso electrophysiological (EP) simulations in conjunction with convolutional neural networks (CNNs) to automate the localization of focal VTs using simulated EGMs.Materials and Methods: A highly detailed 3D torso model was used to simulate ∼4000 focal VTs, evenly distributed across the left ventricle (LV), utilizing a rapid reaction-eikonal environment. Solutions were subsequently combined with lead field computations on the torso to derive accurate electrocardiograms (ECGs) and EGM traces, which were used as inputs to CNNs to localize focal sources. We compared the localization performance of a previously developed CNN architecture (Cartesian probability-based) with our novel CNN algorithm utilizing universal ventricular coordinates (UVCs).Results: Implanted device EGMs successfully localized VT sources with localization error (8.74 mm) comparable to ECG-based localization (6.69 mm). Our novel UVC CNN architecture outperformed the existing Cartesian probability-based algorithm (errors = 4.06 mm and 8.07 mm for ECGs and EGMs, respectively). Overall, localization was relatively insensitive to noise and changes in body compositions; however, displacements in ECG electrodes and CIED leads caused performance to decrease (errors 16–25 mm).Conclusion: EGM recordings from implanted devices may be used to successfully, and robustly, localize focal VT sources, and aid ablation planning.

Fixed-Life or Rechargeable Batteries for Deep Brain Stimulation: Preference and Satisfaction Among Patients With Hyperkinetic Movement Disorders

Background: Deep brain stimulation (DBS) is an established treatment for hyperkinetic movement disorders. Patients undergoing DBS can choose between the use of a rechargeable or non-rechargeable battery for implanted pulse generators (IPG).Objectives: In this study, we aimed to evaluate patient preferences and satisfaction with rechargeable and non-rechargeable batteries for IPGs after undergoing DBS.Methods: Overall, 100 patients with hyperkinetic movement disorders (dystonia: 79, Tourette syndrome: 21) who had undergone DBS took a self-designed questionnaire to assess their satisfaction and experience with the type of battery they had chosen and the factors influencing their choice.Results: Of the participants, 87% were satisfied with the stimulating effects of the treatment as well as the implanted device; 76% had chosen rechargeable devices (r-IPGs), 71.4% of whom recharged the battery themselves. Economic factors were the main reason for choosing both r-IPG and non-rechargeable IPG (nr-IPG). The questionnaire revealed that 66% of the patients checked their r-IPG battery every week. The mean interval for battery recharge was 4.3 days.Conclusions: The majority of the patients were satisfied with their in-service-IPG, regardless of whether it was a r-IPG or nr-IPG. Affordability was the main factor influencing the choice of IPG. The majority of the patients were confident in recharging the battery of their r-IPG themselves; only 11% of patients experienced difficulties. Understanding the recharge process remains difficult for some patients and increasing the number of training sessions for the device may be helpful.

New Ethical and Clinical Challenges in “Closed-Loop” Neuromodulation

Neurostimulation provides a new dimension in the treatment of neurologic disorders. For patients with drug-resistant epilepsy, the Responsive Neurostimulation (RNS) System (NeuroPace, Inc.) provides treatment of seizures with a closed-loop device that continuously records brain activity and provides stimulation designed to reduce seizure frequency over time. The presence of a chronic implanted device that can provide an electrographic record of neural activity provides great opportunities for treatment of seizure disorders and neuroscience research. However, our experience with this device indicates that a number of ethical and clinical challenges arise, and these issues may be applicable to neurotechnology developed for other disease states in the future. We present clinical scenarios based on cases from our center that present clinical or ethical dilemmas. The dilemmas revolve around 4 core themes: (1) electroclinical correlation and dissociation; (2) patient concerns about device capabilities; (3) clinician opportunities and burdens; and (4) data ownership and access. Developing a framework for understanding these issues will be critical as closed-loop neuromodulation is applied to a growing range of neuropsychiatric disorders.