Annual Review of Biomedical Engineering最新文献

Specialized features of vasculature in the central nervous system greatly limit therapeutic treatment options for many neuropathologies. Focused ultrasound, in combination with circulating microbubbles, can be used to transiently and noninvasively increase cerebrovascular permeability with a high level of spatial precision. For minutes to hours following sonication, drugs can be administered systemically to extravasate in the targeted brain regions and exert a therapeutic effect, after which permeability returns to baseline levels. With the wide range of therapeutic agents that can be delivered using this approach and the growing clinical need, focused ultrasound and microbubble (FUS+MB) exposure in the brain has entered human testing to assess safety. This review outlines the use of FUS+MB-mediated cerebrovascular permeability enhancement as a drug delivery technique, details several technical and biological considerations of this approach, summarizes results from the clinical trials conducted to date, and discusses the future direction of the field.

The rise of antibiotic-resistant strains of bacterial pathogens has necessitated the development of new therapeutics. Antimicrobial peptides (AMPs) are a class of compounds with potentially attractive therapeutic properties, including the ability to target specific groups of bacteria. In nature, AMPs exhibit remarkable structural and functional diversity, which may be further enhanced through genetic engineering, high-throughput screening, and chemical modification strategies. In this review, we discuss the molecular mechanisms underlying AMP selectivity and highlight recent computational and experimental efforts to design selectively targeting AMPs. While there has been an extensive effort to find broadly active and highly potent AMPs, it remains challenging to design targeting peptides to discriminate between different bacteria on the basis of physicochemical properties. We also review approaches for measuring AMP activity, point out the challenges faced in assaying for selectivity, and discuss the potential for increasing AMP diversity through chemical modifications.

Since aptamers were first reported in the early 2000s, research on their use for the detection of health-relevant analytical targets has exploded. This review article provides a brief overview of the most recent developments in the field of aptamer-based biosensors for global health applications. The review provides a description of general aptasensing principles and follows up with examples of recent reports of diagnostics-related applications. These applications include detection of proteins and small molecules, circulating cancer cells, whole-cell pathogens, extracellular vesicles, and tissue diagnostics. The review also discusses the main challenges that this growing technology faces in the quest of bringing these new devices from the laboratory to the market.

Cells receive enormous amounts of information from their environment. How they act on this information-by migrating, expressing genes, or relaying signals to other cells-comprises much of the regulatory and self-organizational complexity found across biology. The "parts list" involved in cell signaling is generally well established, but how do these parts work together to decode signals and produce appropriate responses? This fundamental question is increasingly being addressed with optogenetic tools: light-sensitive proteins that enable biologists to manipulate the interaction, localization, and activity state of proteins with high spatial and temporal precision. In this review, we summarize how optogenetics is being used in the pursuit of an answer to this question, outlining the current suite of optogenetic tools available to the researcher and calling attention to studies that increase our understanding of and improve our ability to engineer biology.

The widespread availability of high-performance computing and the popularity of artificial intelligence (AI) with machine learning and deep learning (ML/DL) algorithms at the helm have stimulated the development of many applications involving the use of AI-based techniques in molecular imaging research. Applications reported in the literature encompass various areas, including innovative design concepts in positron emission tomography (PET) instrumentation, quantitative image reconstruction and analysis techniques, computer-aided detection and diagnosis, as well as modeling and prediction of outcomes. This review reflects the tremendous interest in quantitative molecular imaging using ML/DL techniques during the past decade, ranging from the basic principles of ML/DL techniques to the various steps required for obtaining quantitatively accurate PET data, including algorithms used to denoise or correct for physical degrading factors as well as to quantify tracer uptake and metabolic tumor volume for treatment monitoring or radiation therapy treatment planning and response prediction.This review also addresses future opportunities and current challenges facing the adoption of ML/DL approaches and their role in multimodality imaging.

The host-to-host transmission of respiratory infectious diseases is fundamentally enabled by the interaction of pathogens with a variety of fluids (gas or liquid) that shape pathogen encapsulation and emission, transport and persistence in the environment, and new host invasion and infection. Deciphering the mechanisms and fluid properties that govern and promote these steps of pathogen transmission will enable better risk assessment and infection control strategies, and may reveal previously underappreciated ways in which the pathogens might actually adapt to or manipulate the physical and chemical characteristics of these carrier fluids to benefit their own transmission. In this article, I review our current understanding of the mechanisms shaping the fluid dynamics of respiratory infectious diseases.

Additive manufacturing's attributes include print customization, low per-unit cost for small- to mid-batch production, seamless interfacing with mainstream medical 3D imaging techniques, and feasibility to create free-form objects in materials that are biocompatible and biodegradable. Consequently, additive manufacturing is apposite for a wide range of biomedical applications including custom biocompatible implants that mimic the mechanical response of bone, biodegradable scaffolds with engineered degradation rate, medical surgical tools, and biomedical instrumentation. This review surveys the materials, 3D printing methods and technologies, and biomedical applications of metal 3D printing, providing a historical perspective while focusing on the state of the art. It then identifies a number of exciting directions of future growth: (a) the improvement of mainstream additive manufacturing methods and associated feedstock; (b) the exploration of mature, less utilized metal 3D printing techniques; (c) the optimization of additively manufactured load-bearing structures via artificial intelligence; and (d) the creation of monolithic, multimaterial, finely featured, multifunctional implants.

Recreating human organ-level function in vitro is a rapidly evolving field that integrates tissue engineering, stem cell biology, and microfluidic technology to produce 3D organoids. A critical component of all organs is the vasculature. Herein, we discuss general strategies to create vascularized organoids, including common source materials, and survey previous work using vascularized organoids to recreate specific organ functions and simulate tumor progression. Vascularization is not only an essential component of individual organ function but also responsible for coupling the fate of all organs and their functions. While some success in coupling two or more organs together on a single platform has been demonstrated, we argue that the future of vascularized organoid technology lies in creating organoid systems complete with tissue-specific microvasculature and in coupling multiple organs through a dynamic vascular network to create systems that can respond to changing physiological conditions.

Cells of the vascular wall are exquisitely sensitive to changes in their mechanical environment. In healthy vessels, mechanical forces regulate signaling and gene expression to direct the remodeling needed for the vessel wall to maintain optimal function. Major diseases of arteries involve maladaptive remodeling with compromised or lost homeostatic mechanisms. Whereas homeostasis invokes negative feedback loops at multiple scales to mediate mechanobiological stability, disease progression often occurs via positive feedback that generates mechanobiological instabilities. In this review, we focus on the cell biology, wall mechanics, and regulatory pathways associated with arterial health and how changes in these processes lead to disease. We discuss how positive feedback loops arise via biomechanical and biochemical means. We conclude that inflammation plays a central role in overriding homeostatic pathways and suggest future directions for addressing therapeutic needs.