Biofabrication of Living Actuators.

The impact of tissue engineering has extended beyond a traditional focus in medicine to the rapidly growing realm of biohybrid robotics. Leveraging living actuators as functional components in machines has been a central focus of this field, generating a range of compelling demonstrations of robots capable of muscle-powered swimming, walking, pumping, gripping, and even computation. In this review, we highlight key advances in fabricating tissue-scale cardiac and skeletal muscle actuators for a range of functional applications. We discuss areas for future growth including scalable manufacturing, integrated feedback control, and predictive modeling and also propose methods for ensuring inclusive and bioethics-focused pedagogy in this emerging discipline. We hope this review motivates the next generation of biomedical engineers to advance rational design and practical use of living machines for applications ranging from telesurgery to manufacturing to on- and off-world exploration.

Electronic Skin: Opportunities and Challenges in Convergence with Machine Learning.

Recent advancements in soft electronic skin (e-skin) have led to the development of human-like devices that reproduce the skin's functions and physical attributes. These devices are being explored for applications in robotic prostheses as well as for collecting biopotentials for disease diagnosis and treatment, as exemplified by biomedical e-skins. More recently, machine learning (ML) has been utilized to enhance device control accuracy and data processing efficiency. The convergence of e-skin technologies with ML is promoting their translation into clinical practice, especially in healthcare. This review highlights the latest developments in ML-reinforced e-skin devices for robotic prostheses and biomedical instrumentations. We first describe technological breakthroughs in state-of-the-art e-skin devices, emphasizing technologies that achieve skin-like properties. We then introduce ML methods adopted for control optimization and pattern recognition, followed by practical applications that converge the two technologies. Lastly, we briefly discuss the challenges this interdisciplinary research encounters in its clinical and industrial transition.

The use of supramolecular systems in biomedical applications for antimicrobial properties, biocompatibility, and drug delivery.

Supramolecular chemistry is versatile for developing stimuli-responsive, dynamic and multifunctional structures. In the context of biomedical engineering applications, supramolecular assemblies are particularly useful as coatings for they can closely mimic the natural structure and organisation of the extracellular matrix (ECM), they can also fabricate other complex systems like drug delivery systems and bioinks. In the current context of growing medical device-associated complications and the developments in the controlled drug delivery and regenerative medicine fields, supramolecular assemblies are becoming an indispensable part of the biomedical engineering arsenal. This review covers the different supramolecular assemblies in different biomedical applications with a specific focus on antimicrobial coatings, coatings that enhance biocompatibility, surface modifications on implantable medical devices, systems that promote therapeutic efficiency in cancer therapy, and the development of bioinks. The introduced supramolecular systems include multilayer coating by polyelectrolytes, polymers incorporated with nanoparticles, coating simulation of ECM, and drug delivery systems. A perspective on the application of supramolecular systems is also included.

Innovations in bio-engineering and cell-based approaches to address immunological challenges in islet transplantation.

Human allogeneic pancreatic islet transplantation is a life-changing treatment for patients with severe Type 1 Diabetes (T1D) who suffer from hypoglycemia unawareness and high risk of severe hypoglycemia. However, intensive immunosuppression is required to prevent immune rejection of the graft, that may in turn lead to undesirable side effects such as toxicity to the islet cells, kidney toxicity, occurrence of opportunistic infections, and malignancies. The shortage of cadaveric human islet donors further limits islet transplantation as a treatment option for widespread adoption. Alternatively, porcine islets have been considered as another source of insulin-secreting cells for transplantation in T1D patients, though xeno-transplants raise concerns over the risk of endogenous retrovirus transmission and immunological incompatibility. As a result, technological advancements have been made to protect transplanted islets from immune rejection and inflammation, ideally in the absence of chronic immunosuppression, to improve the outcomes and accessibility of allogeneic islet cell replacement therapies. These include the use of microencapsulation or macroencapsulation devices designed to provide an immunoprotective environment using a cell-impermeable layer, preventing immune cell attack of the transplanted cells. Other up and coming advancements are based on the use of stem cells as the starting source material for generating islet cells 'on-demand'. These starting stem cell sources include human induced pluripotent stem cells (hiPSCs) that have been genetically engineered to avoid the host immune response, curated HLA-selected donor hiPSCs that can be matched with recipients within a given population, and multipotent stem cells with natural immune privilege properties. These strategies are developed to provide an immune-evasive cell resource for allogeneic cell therapy. This review will summarize the immunological challenges facing islet transplantation and highlight recent bio-engineering and cell-based approaches aimed at avoiding immune rejection, to improve the accessibility of islet cell therapy and enhance treatment outcomes. Better understanding of the different approaches and their limitations can guide future research endeavors towards developing more comprehensive and targeted strategies for creating a more tolerogenic microenvironment, and improve the effectiveness and sustainability of islet transplantation to benefit more patients.

Medical Microrobots.

Scientists around the world have long aimed to produce miniature robots that can be controlled inside the human body to aid doctors in identifying and treating diseases. Such microrobots hold the potential to access hard-to-reach areas of the body through the natural lumina. Wireless access has the potential to overcome drawbacks of systemic therapy, as well as to enable completely new minimally invasive procedures. The aim of this review is fourfold: first, to provide a collection of valuable anatomical and physiological information on the target working environments together with engineering tools for the design of medical microrobots; second, to provide a comprehensive updated survey of the technological state of the art in relevant classes of medical microrobots; third, to analyze currently available tracking and closed-loop control strategies compatible with the in-body environment; and fourth, to explore the challenges still in place, to steer and inspire future research.

Integrating Upper-Limb Prostheses with the Human Body: Technology Advances, Readiness, and Roles in Human-Prosthesis Interaction.

Significant advances in bionic prosthetics have occurred in the past two decades. The field's rapid expansion has yielded many exciting technologies that can enhance the physical, functional, and cognitive integration of a prosthetic limb with a human. We review advances in the engineering of prosthetic devices and their interfaces with the human nervous system, as well as various surgical techniques for altering human neuromusculoskeletal systems for seamless human-prosthesis integration. We discuss significant advancements in research and clinical translation, focusing on upper limbprosthetics since they heavily rely on user intent for daily operation, although many discussed technologies have been extended to lower limb prostheses as well. In addition, our review emphasizes the roles of advanced prosthetics technologies in complex interactions with humans and the technology readiness levels (TRLs) of individual research advances. Finally, we discuss current gaps and controversies in the field and point out future research directions, guided by TRLs.

Direct Electron Transfer-Type Oxidoreductases for Biomedical Applications.

Among the various types of enzyme-based biosensors, sensors utilizing enzymes capable of direct electron transfer (DET) are recognized as the most ideal. However, only a limited number of redox enzymes are capable of DET with electrodes, that is, dehydrogenases harboring a subunit or domain that functions specifically to accept electrons from the redox cofactor of the catalytic site and transfer the electrons to the external electron acceptor. Such subunits or domains act as built-in mediators for electron transfer between enzymes and electrodes; consequently, such enzymes enable direct electron transfer to electrodes and are designated as DET-type enzymes. DET-type enzymes fall into several categories, including redox cofactors of catalytic reactions, built-in mediators for DET with electrodes and by their protein hierarchic structures, DET-type oxidoreductases with oligomeric structures harboring electron transfer subunits, and monomeric DET-type oxidoreductases harboring electron transfer domains. In this review, we cover the science of DET-type oxidoreductases and their biomedical applications. First, we introduce the structural biology and current understanding of DET-type enzyme reactions. Next, we describe recent technological developments based on DET-type enzymes for biomedical applications, such as biosensors and biochemical energy harvesting for self-powered medical devices. Finally, after discussing how to further engineer and create DET-type enzymes, we address the future prospects for DET-type enzymes in biomedical engineering.

Biomedical Approach of Nanotechnology and Biological Risks: A Mini-Review.

Nanotechnology has played a prominent role in biomedical engineering, offering innovative approaches to numerous treatments. Notable advances have been observed in the development of medical devices, contributing to the advancement of modern medicine. This article briefly discusses key applications of nanotechnology in tissue engineering, controlled drug release systems, biosensors and monitoring, and imaging and diagnosis. The particular emphasis on this theme will result in a better understanding, selection, and technical approach to nanomaterials for biomedical purposes, including biological risks, security, and biocompatibility criteria.

Review: Auxetic Polymer-Based Mechanical Metamaterials for Biomedical Applications.

Over the last three decades but more particularly during the last 5 years, auxetic mechanical metamaterials constructed from precisely architected polymer-based materials have attracted considerable attention due to their fascinating mechanical properties. These materials present a negative Poisson's ratio and therefore unusual mechanical behavior, which has resulted in enhanced static modulus, energy adsorption, and shear resistance, as compared with the bulk properties of polymers. Novel advanced polymer processing and fabrication techniques, and in particular additive manufacturing, allow one to design complex and customizable polymer architectures that are particularly relevant to fabricate auxetic mechanical metamaterials. Although these metamaterials exhibit exotic mechanical properties with potential applications in several engineering fields, biomedical applications seem to be one of the most relevant with a growing number of articles published over recent years. As a result, special focus is needed to understand the potential of these structures and foster theoretical and experimental investigations on the potential benefits of the unusual mechanical properties of these materials on the way to high performance biomedical applications. The present Review provides up to date information on the recent progress of polymer-based auxetic mechanical metamaterials mainly fabricated using additive manufacturing methods with a special focus toward biomedical applications including tissue engineering as well as medical devices including stents and sensors.

Application of a robotics path planning algorithm to assess the risk of mobile bearing dislocation in lateral unicompartmental knee replacement.

Due to ligament laxity, bearing dislocation occurs in 1-6% of Oxford Domed Lateral (ODL) replacements with most dislocations occurring medially. Dislocations were studied using a previously built mechanical rig, however testing using the rig was inefficient. The aim of this study was to develop a better tool that was more reliable and efficient. An established robotics software package, the Open Motion Planning Library, was modified to accept the ODL components. Using a robotics path planning algorithm, the mobile bearing was allowed to find a way out from between the femoral and tibial components i.e. to dislocate. Testing assessed a range of clinically relevant positions of the femoral component relative to the tibial component. Dislocations were labelled as medial, lateral, anterior or posterior depending on the dislocation direction. The Distraction to Dislocation (DD) measured the minimum vertical distraction of the femoral component from the tibial component for a dislocation to occur. Results were validated against the mechanical rig. Statistical analysis of medial dislocation showed excellent agreement with an intraclass correlation value of 0.993 (95% CI 0.982-0.998). All DDs from the dislocation analysis tool were within 1 mm of the mechanical rig DDs with results sharing a remarkably similar trend. The robotics dislocation analysis tool output DDs which were marginally higher than the manual mechanical rig: 0.50 mm anteriorly, 0.25 mm posteriorly and 0.50 mm laterally. Medially, the computational DD differed on average by 0.09 mm (stand deviation: 0.2026 mm). Our study describes the development and validation of a novel robotics dislocation analysis tool, which allows mobile bearing dislocation risk quantification. The tool may also be used to improve surgical implantation parameters and to assess new implant designs that aim to reduce the medial dislocation risk to an acceptable level.

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.

Automatic system for high-throughput and high-sensitivity diagnosis of SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had severe consequences for health and the global economy. To control the transmission, there is an urgent demand for early diagnosis and treatment in the general population. In the present study, an automatic system for SARS-CoV-2 diagnosis is designed and built to deliver high specification, high sensitivity, and high throughput with minimal workforce involvement. The system, set up with cross-priming amplification (CPA) rather than conventional reverse transcription-polymerase chain reaction (RT-PCR), was evaluated using more than 1000 real-world samples for direct comparison. This fully automated robotic system performed SARS-CoV-2 nucleic acid-based diagnosis with 192 samples in under 180 min at 100 copies per reaction in a "specimen in data out" manner. This throughput translates to a daily screening capacity of 800-1000 in an assembly-line manner with limited workforce involvement. The sensitivity of this device could be further improved using a CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based assay, which opens the door to mixed samples, potentially include SARS-CoV-2 variants screening in extensively scaled testing for fighting COVID-19.

Paper microfluidic implementation of loop mediated isothermal amplification for early diagnosis of hepatitis C virus.

The early diagnosis of active hepatitis C virus (HCV) infection remains a significant barrier to the treatment of the disease and to preventing the associated significant morbidity and mortality seen, worldwide. Current testing is delayed due to the high cost, long turnaround times and high expertise needed in centralised diagnostic laboratories. Here we demonstrate a user-friendly, low-cost pan-genotypic assay, based upon reverse transcriptase loop mediated isothermal amplification (RT-LAMP). We developed a prototype device for point-of-care use, comprising a LAMP amplification chamber and lateral flow nucleic acid detection strips, giving a visually-read, user-friendly result in <40 min. The developed assay fulfils the current guidelines recommended by World Health Organisation and is manufactured at minimal cost using simple, portable equipment. Further development of the diagnostic test will facilitate linkage between disease diagnosis and treatment, greatly improving patient care pathways and reducing loss to follow-up, so assisting in the global elimination strategy.

The mechanisms and mechanical energy of human gait initiation from the lower-limb joint level perspective.

This study aims to improve our understanding of gait initiation mechanisms and the lower-limb joint mechanical energy contributions. Healthy subjects were instructed to initiate gait on an instrumented track to reach three self-selected target velocities: slow, normal and fast. Lower-limb joint kinematics and kinetics of the first five strides were analyzed. The results show that the initial lateral weight shift is achieved by hip abduction torque on the lifting leg (leading limb). Before the take-off of the leading limb, the forward body movement is initiated by decreasing ankle plantarflexion torque, which results in an inverted pendulum-like passive forward fall. The hip flexion/extension joint has the greatest positive mechanical energy output in the first stride of the leading limb, while the ankle joint contributes the most positive mechanical energy in the first stride of the trailing limb (stance leg). Our results indicate a strong correlation between control of the frontal plane and the sagittal plane joints during gait initiation. The identified mechanisms and the related data can be used as a guideline for improving gait initiation with wearable robots such as exoskeletons and prostheses.

Portable, open-source solutions for estimating wrist position during reaching in people with stroke.

Arm movement kinematics may provide a more sensitive way to assess neurorehabilitation outcomes than existing metrics. However, measuring arm kinematics in people with stroke can be challenging for traditional optical tracking systems due to non-ideal environments, expense, and difficulty performing required calibration. Here, we present two open-source methods, one using inertial measurement units (IMUs) and another using virtual reality (Vive) sensors, for accurate measurements of wrist position with respect to the shoulder during reaching movements in people with stroke. We assessed the accuracy of each method during a 3D reaching task. We also demonstrated each method's ability to track two metrics derived from kinematics-sweep area and smoothness-in people with chronic stroke. We computed correlation coefficients between the kinematics estimated by each method when appropriate. Compared to a traditional optical tracking system, both methods accurately tracked the wrist during reaching, with mean signed errors of 0.09 ± 1.81 cm and 0.48 ± 1.58 cm for the IMUs and Vive, respectively. Furthermore, both methods' estimated kinematics were highly correlated with each other (p < 0.01). By using relatively inexpensive wearable sensors, these methods may be useful for developing kinematic metrics to evaluate stroke rehabilitation outcomes in both laboratory and clinical environments.

Evaluation of bone formation on orthopedic implant surfaces using an ex-vivo bone bioreactor system.

Recent advances in materials and manufacturing processes have allowed the fabrication of intricate implant surfaces to facilitate bony attachment. However, refinement and evaluation of these new design strategies are hindered by the cost and complications of animal studies, particularly during early iterations in the development process. To address this problem, we have previously constructed and validated an ex-vivo bone bioreactor culture system that can maintain the viability of bone samples for an extended period ex-vivo. In this study, we investigated the mineralization of a titanium wire mesh scaffold under both static and dynamic culturing using our ex vivo bioreactor system. Thirty-six cancellous bone cores were harvested from bovine metatarsals at the time of slaughter and divided into five groups under the following conditions: Group 1) Isolated bone cores placed in static culture, Group 2) Unloaded bone cores placed in static culture in contact with a fiber-mesh metallic scaffold, Group 3) Bone cores placed in contact with a fiber-mesh metallic scaffold under the constant pressure of 150 kPa, Group 4) Bone core placed in contact with a fiber-mesh metallic scaffold and exposed to cyclic loading with continuous perfusion flow of media within the ex-vivo culture system and Group 5) Bone core evaluated on Day 0 to serve as a positive control for comparison with all other groups at weeks 4 and 7. Bone samples within Groups 1-4 were incubated for 4 and 7 weeks and then evaluated using histological examination (H&E) and the Live-Dead assay (Life Technologies). Matrix deposits on the metallic scaffolds were examined with scanning electron microscopy (SEM), while the chemical composition of the matrix was measured using energy-dispersive x-ray spectroscopy (EDX). We found that the viability of bone cores was maintained after seven weeks of loading in our ex vivo system. In addition, SEM images revealed crystallite-like structures on the dynamically loaded metal coupons (Group 4), corresponding to the initial stages of mineralization. EDX results further confirmed the presence of carbon at the interface and calcium phosphates in the matrix. We conclude that a bone bioreactor can be used as an alternate tool for in-vivo bone ingrowth studies of new implant surfaces or coatings.

Recent findings and applications of biomedical engineering for COVID-19 diagnosis: a critical review.

COVID-19 is one of the most severe global health crises that humanity has ever faced. Researchers have restlessly focused on developing solutions for monitoring and tracing the viral culprit, SARS-CoV-2, as vital steps to break the chain of infection. Even though biomedical engineering (BME) is considered a rising field of medical sciences, it has demonstrated its pivotal role in nurturing the maturation of COVID-19 diagnostic technologies. Within a very short period of time, BME research applied to COVID-19 diagnosis has advanced with ever-increasing knowledge and inventions, especially in adapting available virus detection technologies into clinical practice and exploiting the power of interdisciplinary research to design novel diagnostic tools or improve the detection efficiency. To assist the development of BME in COVID-19 diagnosis, this review highlights the most recent diagnostic approaches and evaluates the potential of each research direction in the context of the pandemic.

Tailoring Materials with Specific Wettability in Biomedical Engineering.

As a fundamental feature of solid surfaces, wettability is playing an increasingly important role in our daily life. Benefitting from the inspiration of biological paradigms and the development in manufacturing technology, numerous wettability materials with elaborately designed surface topology and chemical compositions have been fabricated. Based on these advances, wettability materials have found broad technological implications in various fields ranging from academy, industry, agriculture to biomedical engineering. Among them, the practical applications of wettability materials in biomedical-related fields are receiving remarkable researches during the past decades because of the increasing attention to healthcare. In this review, the research progress of materials with specific wettability is discussed. After briefly introducing the underlying mechanisms, the fabrication strategies of artificial materials with specific wettability are described. The emphasis is put on the application progress of wettability biomaterials in biomedical engineering. The prospects for the future trend of wettability materials are also presented.

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.

Development and Application of Medicine-Engineering Integration in the Rehabilitation of Traumatic Brain Injury.

The rapid progress of the combination of medicine and engineering provides better chances for the clinical treatment and healthcare engineering. Traumatic brain injury (TBI) and its related symptoms have become a major global health problem. At present, these techniques has been widely used in the rehabilitation of TBI. In this review article, we summarizes the progress of the combination of medicine and industry in the rehabilitation of traumatic brain injury in recent years, mainly from the following aspects: artificial intelligence (AI), brain-computer interfaces (BCI), noninvasive brain stimulation (NIBS), and wearable-assisted devices. We believe the summary of this article can improve insight into the combination of medicine and industry in the rehabilitation of traumatic brain injury.