Annual Review of Biomedical Engineering最新文献

The 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.

The 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.

Penetrating 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.

One 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.

The 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.

Lipids 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.

Hemolysis (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.

Photoacoustic 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.

Energy-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.

Over 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.