Retinal Prostheses: Engineering and Clinical Perspectives for Vision Restoration.

A retinal prosthesis, also known as a bionic eye, is a device that can be implanted to partially restore vision in patients with retinal diseases that have resulted in the loss of photoreceptors (e.g., age-related macular degeneration and retinitis pigmentosa). Recently, there have been major breakthroughs in retinal prosthesis technology, with the creation of numerous types of implants, including epiretinal, subretinal, and suprachoroidal sensors. These devices can stimulate the remaining cells in the retina with electric signals to create a visual sensation. A literature review of the pre-clinical and clinical studies published between 2017 and 2023 is conducted. This narrative review delves into the retinal anatomy, physiology, pathology, and principles underlying electronic retinal prostheses. Engineering aspects are explored, including electrode-retina alignment, electrode size and material, charge density, resolution limits, spatial selectivity, and bidirectional closed-loop systems. This article also discusses clinical aspects, focusing on safety, adverse events, visual function, outcomes, and the importance of rehabilitation programs. Moreover, there is ongoing debate over whether implantable retinal devices still offer a promising approach for the treatment of retinal diseases, considering the recent emergence of cell-based and gene-based therapies as well as optogenetics. This review compares retinal prostheses with these alternative therapies, providing a balanced perspective on their advantages and limitations. The recent advancements in retinal prosthesis technology are also outlined, emphasizing progress in engineering and the outlook of retinal prostheses. While acknowledging the challenges and complexities of the technology, this article highlights the significant potential of retinal prostheses for vision restoration in individuals with retinal diseases and calls for continued research and development to refine and enhance their performance, ultimately improving patient outcomes and quality of life.

Shape-Memory Polymers Hallmarks and Their Biomedical Applications in the Form of Nanofibers.

Shape-Memory Polymers (SMPs) are considered a kind of smart material able to modify size, shape, stiffness and strain in response to different external (heat, electric and magnetic field, water or light) stimuli including the physiologic ones such as pH, body temperature and ions concentration. The ability of SMPs is to memorize their original shape before triggered exposure and after deformation, in the absence of the stimulus, and to recover their original shape without any help. SMPs nanofibers (SMPNs) have been increasingly investigated for biomedical applications due to nanofiber's favorable properties such as high surface area per volume unit, high porosity, small diameter, low density, desirable fiber orientation and nanoarchitecture mimicking native Extra Cellular Matrix (ECM). This review focuses on the main properties of SMPs, their classification and shape-memory effects. Moreover, advantages in the use of SMPNs and different biomedical application fields are reported and discussed.

Engineering of the current nucleoside-modified mRNA-LNP vaccines against SARS-CoV-2.

Currently, there are over 230 different COVID-19 vaccines under development around the world. At least three decades of scientific development in RNA biology, immunology, structural biology, genetic engineering, chemical modification, and nanoparticle technologies allowed the accelerated development of fully synthetic messenger RNA (mRNA)-based vaccines within less than a year since the first report of a SARS-CoV-2 infection. mRNA-based vaccines have been shown to elicit broadly protective immune responses, with the added advantage of being amenable to rapid and flexible manufacturing processes. This review recapitulates current advances in engineering the first two SARS-CoV-2-spike-encoding nucleoside-modified mRNA vaccines, highlighting the strategies followed to potentiate their effectiveness and safety, thus facilitating an agile response to the current COVID-19 pandemic.

The RADxSM Tech Process: Accelerating Innovation for COVID-19 Testing.

In the wake of the COVID-19 pandemic, the need for rapid and accurate diagnostic testing across populations quickly became evident. In response, the National Institutes of Health (NIH) was determined not only to invest heavily in this area but to change the process by which grant proposals were reviewed and funded in order to spur faster development of viable technologies. The Rapid Acceleration of Diagnostics (RADx) initiative was designed to speed innovation, commercialization, and implementation of potential COVID-19 diagnostic technology. As part of this effort, the RADx Tech initiative focuses on the development, validation, and commercialization of innovative point-of-care, home-based, and clinical lab-based tests that can detect SARS-CoV-2. This effort was enabled through the NIH's National Institute of Biomedical Imaging and Bioengineering (NIBIB) Point-of-Care Technology Research Network (POCTRN).

The newly emerging field of pediatric engineering: Innovation for our next generation.

Neonates, infants, and children have unique physiology and body surface areas that dramatically change during growth and development, and the substantial diversity of complicated pediatric illnesses and rare childhood diseases are distinct from the adult sphere. Unfortunately, medical innovation is generally constrained to retrofitting adult treatment strategies for this heterogeneous population. This conventional, but limited, approach ignores the dynamic biopsychosocial, growth, and developmental complexities that abound, as one progresses through this life cycle from newborn onward toward early adulthood. Forward-thinking solutions are essential to advance the state-of-the-art to address the challenges and unmet clinical needs that are uniquely presented by the pediatric population, and it has become obvious that newly trained engineers are essential for success. These unmet clinical needs and the necessity of new technical skills and expertise give rise to the emergence of an entirely new field of engineering and applied science: Pediatric Engineering. The field of Pediatric Engineering flips conventional wisdom that adult therapies can simply be scaled or successfully modified for children. It commandeers design to suit the specific needs of the child, while anticipating the dynamic growth and development into adulthood. We are growing a new pipeline of educated scientists and engineers who will have developed a unique toolbox of skills that they can use to tackle unmet clinical needs in global pediatric healthcare for years to come.

Visualizing a joint future of neuroscience and neuromorphic engineering.

Recent research resolves the challenging problem of building biophysically plausible spiking neural models that are also capable of complex information processing. This advance creates new opportunities in neuroscience and neuromorphic engineering, which we discussed at an online focus meeting.

Engineering precision nanoparticles for drug delivery.

In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers - systemic, microenvironmental and cellular - that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-size-fits-all solution. As lipid-based, polymeric and inorganic nanoparticles are engineered in increasingly specified ways, they can begin to be optimized for drug delivery in a more personalized manner, entering the era of precision medicine. In this Review, we discuss advanced nanoparticle designs utilized in both non-personalized and precision applications that could be applied to improve precision therapies. We focus on advances in nanoparticle design that overcome heterogeneous barriers to delivery, arguing that intelligent nanoparticle design can improve efficacy in general delivery applications while enabling tailored designs for precision applications, thereby ultimately improving patient outcome overall.

Advanced biomedical applications based on emerging 3D cell culturing platforms.

It is of great value to develop reliable in vitro models for cell biology and toxicology. However, ethical issues and the decreasing number of donors restrict the further use of traditional animal models in various fields, including the emerging fields of tissue engineering and regenerative medicine. The huge gap created by the restrictions in animal models has pushed the development of the increasingly recognized three-dimensional (3D) cell culture, which enables cells to closely simulate authentic cellular behaviour such as close cell-to-cell interactions and can achieve higher functionality. Furthermore, 3D cell culturing is superior to the traditional 2D cell culture, which has obvious limitations and cannot closely mimic the structure and architecture of tissues. In this study, we review several methods used to form 3D multicellular spheroids. The extracellular microenvironment of 3D spheroids plays a role in many aspects of biological sciences, including cell signalling, cell growth, cancer cell generation, and anti-cancer drugs. More recently, they have been explored as basic construction units for tissue and organ engineering. We review this field with a focus on the previous research in different areas using spheroid models, emphasizing aqueous two-phase system (ATPS)-based techniques. Multi-cellular spheroids have great potential in the study of biological systems and can closely mimic the in vivo environment. New technologies to form and analyse spheroids such as the aqueous two-phase system and magnetic levitation are rapidly overcoming the technical limitations of spheroids and expanding their applications in tissue engineering and regenerative medicine.

A Forensic Disassembly of the BIS Monitor.

BACKGROUND: The bispectral index (BIS) monitor has been available for clinical use for >20 years and has had an immense impact on academic activity in Anesthesiology, with >3000 articles referencing the bispectral index. Despite attempts to infer its algorithms by external observation, its operation has nevertheless remained undescribed, in contrast to the algorithms of other less commercially successful monitors of electroencephalogram (EEG) activity under anesthesia. With the expiration of certain key patents, the time is therefore ripe to examine the operation of the monitor on its own terms through careful dismantling, followed by extraction and examination of its internal software. METHODS: An A-2000 BIS Monitor (gunmetal blue case, amber monochrome display) was purchased on the secondary market. After identifying the major data processing and storage components, a set of free or inexpensive tools was used to retrieve and disassemble the monitor's onboard software. The software executes primarily on an ARMv7 microprocessor (Sharp/NXP LH77790B) and a digital signal processor (Texas Instruments TMS320C32). The device software can be retrieved directly from the monitor's hardware by using debugging interfaces that have remained in place from its original development. RESULTS: Critical numerical parameters such as the spectral edge frequency (SEF), total power, and BIS values were retraced from external delivery at the device's serial port back to the point of their calculation in the extracted software. In doing so, the locations of the critical algorithms were determined. To demonstrate the validity of the technique, the algorithms for SEF and total power were disassembled, comprehensively annotated and compared to their theoretically ideal behaviors. A bug was identified in the device's implementation of the SEF algorithm, which can be provoked by a perfectly isoelectric EEG. CONCLUSIONS: This article demonstrates that the electronic design of the A-2000 BIS Monitor does not pose any insuperable obstacles to retrieving its device software in hexadecimal machine code form directly from the motherboard. This software can be reverse engineered through disassembly and decompilation to reveal the methods by which the BIS monitor implements its algorithms, which ultimately must form the definitive statement of its function. Without further revealing any algorithms that might be considered trade secrets, the manufacturer of the BIS monitor should be encouraged to release the device software in its original format to place BIS-related academic literature on a firm theoretical foundation and to promote further academic development of EEG monitoring algorithms.

[The development status of interdisciplinary combination between medicine and engineering in urology: deep integration between medicine and engineering in urology].

Urology is an ancient academic discipline, and its rapid development is due to the combination between medicine and engineering. The development of urology in China is an example of the combination of industry-academia-research based on the progress of science and technology. This paper mainly summarizes the recent advances of interdisciplinary combination between medicine and engineering in urology.

JNER at 15 years: analysis of the state of neuroengineering and rehabilitation.

On JNER's 15th anniversary, this editorial analyzes the state of the field of neuroengineering and rehabilitation. I first discuss some ways that the nature of neurorehabilitation research has evolved in the past 15 years based on my perspective as editor-in-chief of JNER and a researcher in the field. I highlight increasing reliance on advanced technologies, improved rigor and openness of research, and three, related, new paradigms - wearable devices, the Cybathlon competition, and human augmentation studies - indicators that neurorehabilitation is squarely in the age of wearability. Then, I briefly speculate on how the field might make progress going forward, highlighting the need for new models of training and learning driven by big data, better personalization and targeting, and an increase in the quantity and quality of usability and uptake studies to improve translation.

Unsupervised machine-learning classification of electrophysiologically active electrodes during human cognitive task performance.

Identification of active electrodes that record task-relevant neurophysiological activity is needed for clinical and industrial applications as well as for investigating brain functions. We developed an unsupervised, fully automated approach to classify active electrodes showing event-related intracranial EEG (iEEG) responses from 115 patients performing a free recall verbal memory task. Our approach employed new interpretable metrics that quantify spectral characteristics of the normalized iEEG signal based on power-in-band and synchrony measures. Unsupervised clustering of the metrics identified distinct sets of active electrodes across different subjects. In the total population of 11,869 electrodes, our method achieved 97% sensitivity and 92.9% specificity with the most efficient metric. We validated our results with anatomical localization revealing significantly greater distribution of active electrodes in brain regions that support verbal memory processing. We propose our machine-learning framework for objective and efficient classification and interpretation of electrophysiological signals of brain activities supporting memory and cognition.

"On Vivo" and Wearable Clinical Laboratory Testing Devices for Emergency and Critical Care Laboratory Testing.

BACKGROUND: Point-of-care testing (POCT) devices are designed for clinical laboratory testing at the bedside or near the patient and can significantly reduce the turnaround time for laboratory test results. The next generation for clinical laboratory testing may be devices that are worn or attached to the patient. CONTENT: POCT devices that are designed where samples are tested directly on the patient include bilirubinometers, pulse oximeters, breathalyzers (for alcohol and, more recently, cannabinoid detection), transcutaneous blood gas analyses, and novel testing applications such as glucose and tumor signatures following surgical excision. The utility of these devices with special reference for use within the intensive care unit and the emergency department is reviewed. SUMMARY: It is likely that wearable POCT devices will be developed in the future that can meet current and emerging clinical needs. Advancements in biomedical engineering and information technology will be needed in the creation of next-generation devices.

Health Technology Assessment and Biomedical Engineering: Global trends, gaps and opportunities.

The diffusion of medical devices is expanding at an astonishing rate. The increasing number of novel patents per year suggests this growth will continue. In contrast to drugs, medical devices are intrinsically dependent on the environment in which they are used and how they are maintained. This created an unprecedented global need for well-trained biomedical engineers who can help healthcare systems to assess them. The International Federation for Medical and Biological Engineering (IFMBE) is the global scientific society of biomedical engineers in official relations with the United Nations World Health Organisation (WHO) and has been very active in promoting the role of the biomedical engineer in Health Technology Assessment (HTA). The IFMBE Health Technology Assessment Division (HTAD) is the IFMBE operative branch in this field, promoting studies, projects and activities to foster the growth of this specific and very important science sector, including summer schools, training material, an HTA eLearning platform, HTA guidelines, awards and more. This article describes the vision, the mission and the strategy of the HTAD, with a focus on the results achieved and the impact this is having on global policymaking.