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- Volume 25, 2023
Annual Review of Biomedical Engineering - Volume 25, 2023
Volume 25, 2023
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Engineering Therapeutics to Detoxify Hemoglobin, Heme, and Iron
Vol. 25 (2023), pp. 1–21More LessHemolysis (i.e., red blood cell lysis) can increase circulatory levels of cell-free hemoglobin (Hb) and its degradation by-products, namely heme (h) and iron (Fe). Under homeostasis, minor increases in these three hemolytic by-products (Hb/h/Fe) are rapidly scavenged and cleared by natural plasma proteins. Under certain pathophysiological conditions, scavenging systems become overwhelmed, leading to the accumulation of Hb/h/Fe in the circulation. Unfortunately, these species cause various side effects such as vasoconstriction, hypertension, and oxidative organ damage. Therefore, various therapeutics strategies are in development, ranging from supplementation with depleted plasma scavenger proteins to engineered biomimetic protein constructs capable of scavenging multiple hemolytic species. In this review, we briefly describe hemolysis and the characteristics of the major plasma-derived protein scavengers of Hb/h/Fe. Finally, we present novel engineering approaches designed to address the toxicity of these hemolytic by-products.
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Noninvasive Monitoring to Detect Dehydration: Are We There Yet?
Vol. 25 (2023), pp. 23–49More LessThe need for hydration monitoring is significant, especially for the very young and elderly populations who are more vulnerable to becoming dehydrated and suffering from the effects that dehydration brings. This need has been among the drivers of considerable effort in the academic and commercial sectors to provide a means for monitoring hydration status, with a special interest in doing so outside the hospital or clinical setting. This review of emerging technologies provides an overview of many technology approaches that, on a theoretical basis, have sensitivity to water and are feasible as a routine measurement. We review the evidence of technical validation and of their use in humans. Finally, we highlight the essential need for these technologies to be rigorously evaluated for their diagnostic potential, as a necessary step to meet the need for hydration monitoring outside of the clinical environment.
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Neural Plasticity in Sensorimotor Brain–Machine Interfaces
Vol. 25 (2023), pp. 51–76More LessBrain–machine interfaces (BMIs) aim to treat sensorimotor neurological disorders by creating artificial motor and/or sensory pathways. Introducing artificial pathways creates new relationships between sensory input and motor output, which the brain must learn to gain dexterous control. This review highlights the role of learning in BMIs to restore movement and sensation, and discusses how BMI design may influence neural plasticity and performance. The close integration of plasticity in sensory and motor function influences the design of both artificial pathways and will be an essential consideration for bidirectional devices that restore both sensory and motor function.
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Recent Advancements in Electroporation Technologies: From Bench to Clinic
Vol. 25 (2023), pp. 77–100More LessOver the past decade, the increased adoption of electroporation-based technologies has led to an expansion of clinical research initiatives. Electroporation has been utilized in molecular biology for mammalian and bacterial transfection; for food sanitation; and in therapeutic settings to increase drug uptake, for gene therapy, and to eliminate cancerous tissues. We begin this article by discussing the biophysics required for understanding the concepts behind the cell permeation phenomenon that is electroporation. We then review nano- and microscale single-cell electroporation technologies before scaling up to emerging in vivo applications.
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Bioelectronic Sensor Nodes for the Internet of Bodies
Vol. 25 (2023), pp. 101–129More LessEnergy-efficient sensing with physically secure communication for biosensors on, around, and within the human body is a major area of research for the development of low-cost health care devices, enabling continuous monitoring and/or secure perpetual operation. When used as a network of nodes, these devices form the Internet of Bodies, which poses challenges including stringent resource constraints, simultaneous sensing and communication, and security vulnerabilities. Another major challenge is to find an efficient on-body energy-harvesting method to support the sensing, communication, and security submodules. Due to limitations in the amount of energy harvested, we require a reduction in energy consumed per unit information, making the use of in-sensor analytics and processing imperative. In this article, we review the challenges and opportunities of low-power sensing, processing, and communication with possible powering modalities for future biosensor nodes. Specifically, we analyze, compare, and contrast (a) different sensing mechanisms such as voltage/current domain versus time domain, (b) low-power, secure communication modalities including wireless techniques and human body communication, and (c) different powering techniques for wearable devices and implants.
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Predictive Models for Health Deterioration: Understanding Disease Pathways for Personalized Medicine
Vol. 25 (2023), pp. 131–156More LessArtificial intelligence (AI) and machine learning (ML) methods are currently widely employed in medicine and healthcare. A PubMed search returns more than 100,000 articles on these topics published between 2018 and 2022 alone. Notwithstanding several recent reviews in various subfields of AI and ML in medicine, we have yet to see a comprehensive review around the methods’ use in longitudinal analysis and prediction of an individual patient's health status within a personalized disease pathway. This review seeks to fill that gap. After an overview of the AI and ML methods employed in this field and of specific medical applications of models of this type, the review discusses the strengths and limitations of current studies and looks ahead to future strands of research in this field. We aim to enable interested readers to gain a detailed impression of the research currently available and accordingly plan future work around predictive models for deterioration in health status.
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Epitranscriptional Regulation: From the Perspectives of Cardiovascular Bioengineering
Vol. 25 (2023), pp. 157–184More LessThe central dogma of gene expression involves DNA transcription to RNA and RNA translation into protein. As key intermediaries and modifiers, RNAs undergo various forms of modifications such as methylation, pseudouridylation, deamination, and hydroxylation. These modifications, termed epitranscriptional regulations, lead to functional changes in RNAs. Recent studies have demonstrated crucial roles for RNA modifications in gene translation, DNA damage response, and cell fate regulation. Epitranscriptional modifications play an essential role in development, mechanosensing, atherogenesis, and regeneration in the cardiovascular (CV) system, and their elucidation is critically important to understanding the molecular mechanisms underlying CV physiology and pathophysiology. This review aims at providing biomedical engineers with an overview of the epitranscriptome landscape, related key concepts, recent findings in epitranscriptional regulations, and tools for epitranscriptome analysis. The potential applications of this important field in biomedical engineering research are discussed.
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Emerging Penetrating Neural Electrodes: In Pursuit of Large Scale and Longevity
Lan Luan, Rongkang Yin, Hanlin Zhu, and Chong XieVol. 25 (2023), pp. 185–205More LessPenetrating neural electrodes provide a powerful approach to decipher brain circuitry by allowing for time-resolved electrical detections of individual action potentials. This unique capability has contributed tremendously to basic and translational neuroscience, enabling both fundamental understandings of brain functions and applications of human prosthetic devices that restore crucial sensations and movements. However, conventional approaches are limited by the scarce number of available sensing channels and compromised efficacy over long-term implantations. Recording longevity and scalability have become the most sought-after improvements in emerging technologies. In this review, we discuss the technological advances in the past 5–10 years that have enabled larger-scale, more detailed, and longer-lasting recordings of neural circuits at work than ever before. We present snapshots of the latest advances in penetration electrode technology, showcase their applications in animal models and humans, and outline the underlying design principles and considerations to fuel future technological development.
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Photoacoustic Imaging and Characterization of Bone in Medicine: Overview, Applications, and Outlook
Vol. 25 (2023), pp. 207–232More LessPhotoacoustic techniques have shown promise in identifying molecular changes in bone tissue and visualizing tissue microstructure. This capability represents significant advantages over gold standards (i.e., dual-energy X-ray absorptiometry) for bone evaluation without requiring ionizing radiation. Instead, photoacoustic imaging uses light to penetrate through bone, followed by acoustic pressure generation, resulting in highly sensitive optical absorption contrast in deep biological tissues. This review covers multiple bone-related photoacoustic imaging contributions to clinical applications, spanning bone cancer, joint pathologies, spinal disorders, osteoporosis, bone-related surgical guidance, consolidation monitoring, and transsphenoidal and transcranial imaging. We also present a summary of photoacoustic-based techniques for characterizing biomechanical properties of bone, including temperature, guided waves, spectral parameters, and spectroscopy. We conclude with a future outlook based on the current state of technological developments, recent achievements, and possible new directions.
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Nanotechnologies for Physiology-Informed Drug Delivery to the Lymphatic System
Vol. 25 (2023), pp. 233–256More LessAccompanying the increasing translational impact of immunotherapeutic strategies to treat and prevent disease has been a broadening interest across both bioscience and bioengineering in the lymphatic system. Herein, the lymphatic system physiology, ranging from its tissue structures to immune functions and effects, is described. Design principles and engineering approaches to analyze and manipulate this tissue system in nanoparticle-based drug delivery applications are also elaborated.
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Thinking Beyond the Device: An Overview of Human- and Equity-Centered Approaches for Health Technology Design
Vol. 25 (2023), pp. 257–280More LessA shift in the traditional technocentric view of medical device design to a human-centered one is needed to bridge existing translational gaps and improve health equity. To ensure the successful and equitable adoption of health technology innovations, engineers must think beyond the device and the direct end user and must seek a more holistic understanding of broader stakeholder needs and the intended context of use early in a design process. The objectives of this review article are (a) to provide rationale for the need to incorporate meaningful stakeholder analysis and contextual investigation in health technology development and biomedical engineering pedagogy, (b) to review existing frameworks and human- and equity-centered approaches to stakeholder engagement and contextual investigation for improved adoption of innovative technologies, and (c) to present case studyexamples of medical device design that apply these approaches to bridge the gaps between biomedical engineers and the contexts for which they are designing.
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Analytical Techniques for Single-Cell Biochemical Assays of Lipids
Vol. 25 (2023), pp. 281–309More LessLipids are essential cellular components forming membranes, serving as energy reserves, and acting as chemical messengers. Dysfunction in lipid metabolism and signaling is associated with a wide range of diseases including cancer and autoimmunity. Heterogeneity in cell behavior including lipid signaling is increasingly recognized as a driver of disease and drug resistance. This diversity in cellular responses as well as the roles of lipids in health and disease drive the need to quantify lipids within single cells. Single-cell lipid assays are challenging due to the small size of cells (∼1 pL) and the large numbers of lipid species present at concentrations spanning orders of magnitude. A growing number of methodologies enable assay of large numbers of lipid analytes, perform high-resolution spatial measurements, or permit highly sensitive lipid assays in single cells. Covered in this review are mass spectrometry, Raman imaging, and fluorescence-based assays including microscopy and microseparations.
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Sex as a Biological Variable in Tissue Engineering and Regenerative Medicine
Vol. 25 (2023), pp. 311–331More LessAlthough sex differences have been noted in cellular function and behavior, therapy efficacy, and disease incidence and outcomes, the adoption of sex as a biological variable in tissue engineering and regenerative medicine remains limited. Furthering the development of personalized, precision medicine requires considering biological sex at the bench and in the clinic. This review provides the basis for considering biological sex when designing tissue-engineered constructs and regenerative therapies by contextualizing sex as a biological variable within the tissue engineering triad of cells, matrices, and signals. To achieve equity in biological sex within medicine requires a cultural shift in science and engineering research, with active engagement by researchers, clinicians, companies, policymakers, and funding agencies.
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Engineered Compounds to Control Ice Nucleation and Recrystallization
Vol. 25 (2023), pp. 333–362More LessOne of the greatest concerns in the subzero storage of cells, tissues, and organs is the ability to control the nucleation or recrystallization of ice. In nature, evidence of these processes, which aid in sustaining internal temperatures below the physiologic freezing point for extended periods of time, is apparent in freeze-avoidant and freeze-tolerant organisms. After decades of studying these proteins, we now have easily accessible compounds and materials capable of recapitulating the mechanisms seen in nature for biopreser-vation applications. The output from this burgeoning area of research can interact synergistically with other novel developments in the field of cryobiology, making it an opportune time for a review on this topic.
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Current Trends in Anti-Aging Strategies
Vol. 25 (2023), pp. 363–385More LessThe process of aging manifests from a highly interconnected network of biological cascades resulting in the degradation and breakdown of every living organism over time. This natural development increases risk for numerous diseases and can be debilitating. Academic and industrial investigators have long sought to impede, or potentially reverse, aging in the hopes of alleviating clinical burden, restoring functionality, and promoting longevity. Despite widespread investigation, identifying impactful therapeutics has been hindered by narrow experimental validation and the lack of rigorous study design. In this review, we explore the current understanding of the biological mechanisms of aging and how this understanding both informs and limits interpreting data from experimental models based on these mechanisms. We also discuss select therapeutic strategies that have yielded promising data in these model systems with potential clinical translation. Lastly, we propose a unifying approach needed to rigorously vet current and future therapeutics and guide evaluation toward efficacious therapies.
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Neurotechnology for Pain
Vol. 25 (2023), pp. 387–412More LessNeurotechnologies for treating pain rely on electrical stimulation of the central or peripheral nervous system to disrupt or block pain signaling and have been commercialized to treat a variety of pain conditions. While their adoption is accelerating, neurotechnologies are still frequently viewed as a last resort, after many other treatment options have been explored. We review the pain conditions commonly treated with electrical stimulation, as well as the specific neurotechnologies used for treating those conditions. We identify barriers to adoption, including a limited understanding of mechanisms of action, inconsistent efficacy across patients, and challenges related to selectivity of stimulation and off-target side effects. We describe design improvements that have recently been implemented, as well as some cutting-edge technologies that may address the limitations of existing neurotechnologies. Addressing these challenges will accelerate adoption and change neurotechnologies from last-line to first-line treatments for people living with chronic pain.
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Label-Free Optical Metabolic Imaging in Cells and Tissues
Vol. 25 (2023), pp. 413–443More LessOver the last half century, the autofluorescence of the metabolic cofactors NADH (reduced nicotinamide adenine dinucleotide) and FAD (flavin adenine dinucleotide) has been quantified in a variety of cell types and disease states. With the spread of nonlinear optical microscopy techniques in biomedical research, NADH and FAD imaging has offered an attractive solution to noninvasively monitor cell and tissue status and elucidate dynamic changes in cell or tissue metabolism. Various tools and methods to measure the temporal, spectral, and spatial properties of NADH and FAD autofluorescence have been developed. Specifically, an optical redox ratio of cofactor fluorescence intensities and NADH fluorescence lifetime parameters have been used in numerous applications, but significant work remains to mature this technology for understanding dynamic changes in metabolism. This article describes the current understanding of our optical sensitivity to different metabolic pathways and highlights current challenges in the field. Recent progress in addressing these challenges and acquiring more quantitative information in faster and more metabolically relevant formats is also discussed.
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Previous Volumes
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Volume 26 (2024)
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Volume 25 (2023)
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Volume 24 (2022)
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Volume 23 (2021)
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Volume 22 (2020)
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Volume 21 (2019)
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Volume 20 (2018)
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Volume 19 (2017)
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Volume 18 (2016)
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Volume 17 (2015)
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Volume 16 (2014)
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Volume 15 (2013)
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Volume 14 (2012)
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Volume 13 (2011)
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Volume 12 (2010)
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Volume 11 (2009)
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Volume 10 (2008)
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Volume 9 (2007)
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Volume 8 (2006)
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Volume 7 (2005)
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Volume 6 (2004)
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Volume 5 (2003)
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Volume 4 (2002)
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Volume 3 (2001)
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Volume 2 (2000)
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Volume 1 (1999)
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Volume 0 (1932)