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  • Exploring Dynamics and Structure of Biomolecules, Cryoprotectants, and Water Using Molecular Dynamics Simulations: Implications for Biostabilization and Biopreservation
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Lindong Weng, Shannon L. Stott, Mehmet Toner

    Successful stabilization and preservation of biological materials often utilize low temperatures and dehydration to arrest molecular motion. Cryoprotectants are routinely employed to help the biological entities survive the physicochemical and mechanical stresses induced by cold or dryness. Molecular interactions between biomolecules, cryoprotectants, and water fundamentally determine the outcomes of preservation. The optimization of assays using the empirical approach is often limited in structural and temporal resolution, whereas classical molecular dynamics simulations can provide a cost-effective glimpse into the atomic-level structure and interaction of individual molecules that dictate macroscopic behavior. Computational research on biomolecules, cryoprotectants, and water has provided invaluable insights into the development of new cryoprotectants and the optimization of preservation methods. We describe the rapidly evolving state of the art of molecular simulations of these complex systems, summarize the molecular-scale protective and stabilizing mechanisms, and discuss the challenges that motivate continued innovation in this field.

    更新日期:2019-11-18
  • Current and Future Considerations in the Use of Mechanical Circulatory Support Devices: An Update, 2008–2018
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Marc A. Simon, Timothy N. Bachman, John Watson, J. Timothy Baldwin, William R. Wagner, Harvey S. Borovetz

    Our review in the 2008 volume of this journal detailed the use of mechanical circulatory support (MCS) for treatment of heart failure (HF). MCS initially utilized bladder-based blood pumps generating pulsatile flow; these pulsatile flow pumps have been supplanted by rotary blood pumps, in which cardiac support is generated via the high-speed rotation of computationally designed blading. Different rotary pump designs have been evaluated for their safety, performance, and efficacy in clinical trials both in the United States and internationally. The reduced size of the rotary pump designs has prompted research and development toward the design of MCS suitable for infants and children. The past decade has witnessed efforts focused on tissue engineering–based therapies for the treatment of HF. This review explores the current state and future opportunities of cardiac support therapies within our larger understanding of the treatment options for HF.

    更新日期:2019-11-18
  • Prevention of Opioid Abuse and Treatment of Opioid Addiction: Current Status and Future Possibilities
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Kinam Park, Andrew Otte

    Prescription opioid medications have seen a dramatic rise in misuse and abuse, leading regulators and scientists to develop policies and abuse-deterrent technologies to combat the current opioid epidemic. These abuse-deterrent formulations (ADFs) are intended to deter physical and chemical tampering of opioid-based products, while still providing safe and effective delivery for therapeutic purposes. Even though formulations with varying abuse-deterrent technologies have been approved, questions remain about their effectiveness. While these formulations provide a single means to combat the epidemic, a greater emphasis should be placed on formulations for treatment of addiction and overdose to help those struggling with opioid dependence. This article analyzes various ADFs currently in clinical use and explores potential novel systems for treatment of addiction and prevention of overdose.

    更新日期:2019-11-18
  • The Biocompatibility Challenges in the Total Artificial Heart Evolution
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Eleonora Dal Sasso, Andrea Bagno, Silvia T.G. Scuri, Gino Gerosa, Laura Iop

    There are limited therapeutic options for final treatment of end-stage heart failure. Among them, implantation of a total artificial heart (TAH) is an acceptable strategy when suitable donors are not available. TAH development began in the 1930s, followed by a dramatic evolution of the actuation mechanisms operating the mechanical pumps. Nevertheless, the performance of TAHs has not yet been optimized, mainly because of the low biocompatibility of the blood-contacting surfaces. Low hemocompatibility, calcification, and sensitivity to infections seriously affect the success of TAHs. These unsolved issues have led to the withdrawal of many prototypes during preclinical phases of testing. This review offers a comprehensive analysis of the pathophysiological events that may occur in the materials that compose TAHs developed to date. In addition, this review illustrates bioengineering strategies to prevent these events and describes the most significant steps toward the achievement of a fully biocompatible TAH.

    更新日期:2019-11-18
  • New Sensor and Wearable Technologies to Aid in the Diagnosis and Treatment Monitoring of Parkinson's Disease
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Mariana H.G. Monje, Guglielmo Foffani, José Obeso, Álvaro Sánchez-Ferro

    Parkinson's disease (PD) is a degenerative disorder of the brain characterized by the impairment of the nigrostriatal system. This impairment leads to specific motor manifestations (i.e., bradykinesia, tremor, and rigidity) that are assessed through clinical examination, scales, and patient-reported outcomes. New sensor-based and wearable technologies are progressively revolutionizing PD care by objectively measuring these manifestations and improving PD diagnosis and treatment monitoring. However, their use is still limited in clinical practice, perhaps because of the absence of external validation and standards for their continuous use at home. In the near future, these systems will progressively complement traditional tools and revolutionize the way we diagnose and monitor patients with PD.

    更新日期:2019-11-18
  • Hydrogel-Based Strategies to Advance Therapies for Chronic Skin Wounds
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Lucília P. da Silva, Rui L. Reis, Vitor M. Correlo, Alexandra P. Marques

    Chronic skin wounds are the leading cause of nontraumatic foot amputations worldwide and present a significant risk of morbidity and mortality due to the lack of efficient therapies. The intrinsic characteristics of hydrogels allow them to benefit cutaneous healing essentially by supporting a moist environment. This property has long been explored in wound management to aid in autolytic debridement. However, chronic wounds require additional therapeutic features that can be provided by a combination of hydrogels with biochemical mediators or cells, promoting faster and better healing. We survey hydrogel-based approaches with potential to improve the healing of chronic wounds by reviewing their effects as observed in preclinical models. Topics covered include strategies to ablate infection and resolve inflammation, the delivery of bioactive agents to accelerate healing, and tissue engineering approaches for skin regeneration. The article concludes by considering the relevance of treating chronic skin wounds using hydrogel-based strategies.

    更新日期:2019-11-18
  • Biomaterials: Been There, Done That, and Evolving into the Future
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Buddy D. Ratner

    Biomaterials as we know them today had their origins in the late 1940s with off-the-shelf commercial polymers and metals. The evolution of materials for medical applications from these simple origins has been rapid and impactful. This review relates some of the early history; addresses concerns after two decades of development in the twenty-first century; and discusses how advanced technologies in both materials science and biology will address concerns, advance materials used at the biointerface, and improve outcomes for patients.

    更新日期:2019-11-18
  • Frontiers of Medical Robotics: From Concept to Systems to Clinical Translation
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Jocelyne Troccaz, Giulio Dagnino, Guang-Zhong Yang

    Medical robotics is poised to transform all aspects of medicine—from surgical intervention to targeted therapy, rehabilitation, and hospital automation. A key area is the development of robots for minimally invasive interventions. This review provides a detailed analysis of the evolution of interventional robots and discusses how the integration of imaging, sensing, and robotics can influence the patient care pathway toward precision intervention and patient-specific treatment. It outlines how closer coupling of perception, decision, and action can lead to enhanced dexterity, greater precision, and reduced invasiveness. It provides a critical analysis of some of the key interventional robot platforms developed over the years and their relative merit and intrinsic limitations. The review also presents a future outlook for robotic interventions and emerging trends in making them easier to use, lightweight, ergonomic, and intelligent, and thus smarter, safer, and more accessible for clinical use.

    更新日期:2019-11-18
  • Challenges and Opportunities in the Design of Liver-on-Chip Microdevices
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Avner Ehrlich, Daniel Duche, Gladys Ouedraogo, Yaakov Nahmias

    The liver is the central hub of xenobiotic metabolism and consequently the organ most prone to cosmetic- and drug-induced toxicity. Failure to detect liver toxicity or to assess compound clearance during product development is a major cause of postmarketing product withdrawal, with disastrous clinical and financial consequences. While small animals are still the preferred model in drug development, the recent ban on animal use in the European Union created a pressing need to develop precise and efficient tools to detect human liver toxicity during cosmetic development. This article includes a brief review of liver development, organization, and function and focuses on the state of the art of long-term cell culture, including hepatocyte cell sources, heterotypic cell–cell interactions, oxygen demands, and culture medium formulation. Finally, the article reviews emerging liver-on-chip devices and discusses the advantages and pitfalls of individual designs. The goal of this review is to provide a framework to design liver-on-chip devices and criteria with which to evaluate this emerging technology.

    更新日期:2019-11-18
  • Programming Stimuli-Responsive Behavior into Biomaterials
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Barry A. Badeau, Cole A. DeForest

    Stimuli-responsive materials undergo triggered changes when presented with specific environmental cues. These dynamic systems can leverage biological signals found locally within the body as well as exogenous cues administered with spatiotemporal control, providing powerful opportunities in next-generation diagnostics and personalized medicine. Here, we review the synthetic and strategic advances used to impart diverse responsiveness to a wide variety of biomaterials. Categorizing systems on the basis of material type, number of inputs, and response mechanism, we examine past and ongoing efforts toward endowing biomaterials with customizable sensitivity. We draw an analogy to computer science, whereby a stimuli-responsive biomaterial transduces a set of inputs into a functional output as governed by a user-specified logical operator. We discuss Boolean and non-Boolean operations, as well as the various chemical and physical modes of signal transduction. Finally, we examine current limitations and promising directions in the ongoing development of programmable stimuli-responsive biomaterials.

    更新日期:2019-11-18
  • Mechanobiology of Macrophages: How Physical Factors Coregulate Macrophage Plasticity and Phagocytosis
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Nikhil Jain, Jens Moeller, Viola Vogel

    In addition to their early-recognized functions in host defense and the clearance of apoptotic cell debris, macrophages play vital roles in tissue development, homeostasis, and repair. If misregulated, they steer the progression of many inflammatory diseases. Much progress has been made in understanding the mechanisms underlying macrophage signaling, transcriptomics, and proteomics, under physiological and pathological conditions. Yet, the detailed mechanisms that tune circulating monocytes/macrophages and tissue-resident macrophage polarization, differentiation, specification, and their functional plasticity remain elusive. We review how physical factors affect macrophage phenotype and function, including how they hunt for particles and pathogens, as well as the implications for phagocytosis, autophagy, and polarization from proinflammatory to prohealing phenotype. We further discuss how this knowledge can be harnessed in regenerative medicine and for the design of new drugs and immune-modulatory drug delivery systems, biomaterials, and tissue scaffolds.

    更新日期:2019-11-18
  • Skin-Mountable Biosensors and Therapeutics: A Review
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Eun Kwang Lee, Min Ku Kim, Chi Hwan Lee

    Miniaturization of electronic components and advances in flexible and stretchable materials have stimulated the development of wearable health care systems that can reflect and monitor personal health status by health care professionals. New skin-mountable devices that offer seamless contact onto the human skin, even under large deformations by natural motions of the wearer, provide a route for both high-fidelity monitoring and patient-controlled therapy. This article provides an overview of several important aspects of skin-mountable devices and their applications in many medical settings and clinical practices. We comprehensively describe various transdermal sensors and therapeutic systems that are capable of detecting physical, electrophysiological, and electrochemical responses and/or providing electrical and thermal therapies and drug delivery services, and we discuss the current challenges, opportunities, and future perspectives in the field. Finally, we present ways to protect the embedded electronic components of skin-mountable devices from the environment by use of mechanically soft packaging materials.

    更新日期:2019-11-18
  • Digital Manufacturing for Microfluidics
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Arman Naderi, Nirveek Bhattacharjee, Albert Folch

    The microfluidics field is at a critical crossroads. The vast majority of microfluidic devices are presently manufactured using micromolding processes that work very well for a reduced set of biocompatible materials, but the time, cost, and design constraints of micromolding hinder the commercialization of many devices. As a result, the dissemination of microfluidic technology—and its impact on society—is in jeopardy. Digital manufacturing (DM) refers to a family of computer-centered processes that integrate digital three-dimensional (3D) designs, automated (additive or subtractive) fabrication, and device testing in order to increase fabrication efficiency. Importantly, DM enables the inexpensive realization of 3D designs that are impossible or very difficult to mold. The adoption of DM by microfluidic engineers has been slow, likely due to concerns over the resolution of the printers and the biocompatibility of the resins. In this article, we review and discuss the various printer types, resolution, biocompatibility issues, DM microfluidic designs, and the bright future ahead for this promising, fertile field.

    更新日期:2019-11-18
  • Single-Cell Omics Analyses Enabled by Microchip Technologies
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Yanxiang Deng, Amanda Finck, Rong Fan

    Single-cell omics studies provide unique information regarding cellular heterogeneity at various levels of the molecular biology central dogma. This knowledge facilitates a deeper understanding of how underlying molecular and architectural changes alter cell behavior, development, and disease processes. The emerging microchip-based tools for single-cell omics analysis are enabling the evaluation of cellular omics with high throughput, improved sensitivity, and reduced cost. We review state-of-the-art microchip platforms for profiling genomics, epigenomics, transcriptomics, proteomics, metabolomics, and multi-omics at single-cell resolution. We also discuss the background of and challenges in the analysis of each molecular layer and integration of multiple levels of omics data, as well as how microchip-based methodologies benefit these fields. Additionally, we examine the advantages and limitations of these approaches. Looking forward, we describe additional challenges and future opportunities that will facilitate the improvement and broad adoption of single-cell omics in life science and medicine.

    更新日期:2019-11-18
  • Frontiers in Cryo Electron Microscopy of Complex Macromolecular Assemblies
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Jana Ognjenović, Reinhard Grisshammer, Sriram Subramaniam

    In recent years, cryo electron microscopy (cryo-EM) technology has been transformed with the development of better instrumentation, direct electron detectors, improved methods for specimen preparation, and improved software for data analysis. Analyses using single-particle cryo-EM methods have enabled determination of structures of proteins with sizes smaller than 100 kDa and resolutions of ∼2 Å in some cases. The use of electron tomography combined with subvolume averaging is beginning to allow the visualization of macromolecular complexes in their native environment in unprecedented detail. As a result of these advances, solutions to many intractable challenges in structural and cell biology, such as analysis of highly dynamic soluble and membrane-embedded protein complexes or partially ordered protein aggregates, are now within reach. Recent reports of structural studies of G protein–coupled receptors, spliceosomes, and fibrillar specimens illustrate the progress that has been made using cryo-EM methods, and are the main focus of this review.

    更新日期:2019-11-18
  • A Contemporary Look at Biomechanical Models of Myocardium
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Reza Avazmohammadi, João S. Soares, David S. Li, Samarth S. Raut, Robert C. Gorman, Michael S. Sacks

    Understanding and predicting the mechanical behavior of myocardium under healthy and pathophysiological conditions are vital to developing novel cardiac therapies and promoting personalized interventions. Within the past 30 years, various constitutive models have been proposed for the passive mechanical behavior of myocardium. These models cover a broad range of mathematical forms, microstructural observations, and specific test conditions to which they are fitted. We present a critical review of these models, covering both phenomenological and structural approaches, and their relations to the underlying structure and function of myocardium. We further explore the experimental and numerical techniques used to identify the model parameters. Next, we provide a brief overview of continuum-level electromechanical models of myocardium, with a focus on the methods used to integrate the active and passive components of myocardial behavior. We conclude by pointing to future directions in the areas of optimal form as well as new approaches for constitutive modeling of myocardium.

    更新日期:2019-11-18
  • The Driving Force: Nuclear Mechanotransduction in Cellular Function, Fate, and Disease
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Melanie Maurer, Jan Lammerding

    Cellular behavior is continuously affected by microenvironmental forces through the process of mechanotransduction, in which mechanical stimuli are rapidly converted to biochemical responses. Mounting evidence suggests that the nucleus itself is a mechanoresponsive element, reacting to cytoskeletal forces and mediating downstream biochemical responses. The nucleus responds through a host of mechanisms, including partial unfolding, conformational changes, and phosphorylation of nuclear envelope proteins; modulation of nuclear import/export; and altered chromatin organization, resulting in transcriptional changes. It is unclear which of these events present direct mechanotransduction processes and which are downstream of other mechanotransduction pathways. We critically review and discuss the current evidence for nuclear mechanotransduction, particularly in the context of stem cell fate, a largely unexplored topic, and in disease, where an improved understanding of nuclear mechanotransduction is beginning to open new treatment avenues. Finally, we discuss innovative technological developments that will allow outstanding questions in the rapidly growing field of nuclear mechanotransduction to be answered.

    更新日期:2019-11-18
  • Controlling Matter at the Molecular Scale with DNA Circuits
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Dominic Scalise, Rebecca Schulman

    In recent years, a diverse set of mechanisms have been developed that allow DNA strands with specific sequences to sense information in their environment and to control material assembly, disassembly, and reconfiguration. These sequences could serve as the inputs and outputs for DNA computing circuits, enabling DNA circuits to act as chemical information processors to program complex behavior in chemical and material systems. This review describes processes that can be sensed and controlled within such a paradigm. Specifically, there are interfaces that can release strands of DNA in response to chemical signals, wavelengths of light, pH, or electrical signals, as well as DNA strands that can direct the self-assembly and dynamic reconfiguration of DNA nanostructures, regulate particle assemblies, control encapsulation, and manipulate materials including DNA crystals, hydrogels, and vesicles. These interfaces have the potential to enable chemical circuits to exert algorithmic control over responsive materials, which may ultimately lead to the development of materials that grow, heal, and interact dynamically with their environments.

    更新日期:2019-11-18
  • The Meniscus in Normal and Osteoarthritic Tissues: Facing the Structure Property Challenges and Current Treatment Trends
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Caroline A. Murphy, Atul K. Garg, Joana Silva-Correia, Rui L. Reis, Joaquim M. Oliveira, Maurice N. Collins

    The treatment of meniscus injuries has recently been facing a paradigm shift toward the field of tissue engineering, with the aim of regenerating damaged and diseased menisci as opposed to current treatment techniques. This review focuses on the structure and mechanics associated with the meniscus. The meniscus is defined in terms of its biological structure and composition. Biomechanics of the meniscus are discussed in detail, as an understanding of the mechanics is fundamental for the development of new meniscal treatment strategies. Key meniscal characteristics such as biological function, damage (tears), and disease are critically analyzed. The latest technologies behind meniscal repair and regeneration are assessed.

    更新日期:2019-11-18
  • Intracranial Pressure and Intracranial Elastance Monitoring in Neurocritical Care
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Thomas Heldt, Tommaso Zoerle, Daniel Teichmann, Nino Stocchetti

    Patients with acute brain injuries tend to be physiologically unstable and at risk of rapid and potentially life-threatening decompensation due to shifts in intracranial compartment volumes and consequent intracranial hypertension. Invasive intracranial pressure (ICP) monitoring therefore remains a cornerstone of modern neurocritical care, despite the attendant risks of infection and damage to brain tissue arising from the surgical placement of a catheter or pressure transducer into the cerebrospinal fluid or brain tissue compartments. In addition to ICP monitoring, tracking of the intracranial capacity to buffer shifts in compartment volumes would help in the assessment of patient state, inform clinical decision making, and guide therapeutic interventions. We review the anatomy, physiology, and current technology relevant to clinical management of patients with acute brain injury and outline unmet clinical needs to advance patient monitoring in neurocritical care.

    更新日期:2019-11-18
  • Human Positron Emission Tomography Neuroimaging
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2019-06-05
    Jacob M. Hooker, Richard E. Carson

    Neuroimaging with positron emission tomography (PET) is the most powerful tool for understanding pharmacology, neurochemistry, and pathology in the living human brain. This technology combines high-resolution scanners to measure radioactivity throughout the human body with specific, targeted radioactive molecules, which allow measurements of a myriad of biological processes in vivo. While PET brain imaging has been active for almost 40 years, the pace of development for neuroimaging tools, known as radiotracers, and for quantitative analytical techniques has increased dramatically over the past decade. Accordingly, the fundamental questions that can be addressed with PET have expanded in basic neurobiology, psychiatry, neurology, and related therapeutic development. In this review, we introduce the field of human PET neuroimaging, some of its conceptual underpinnings, and motivating questions. We highlight some of the more recent advances in radiotracer development, quantitative modeling, and applications of PET to the study of the human brain.

    更新日期:2019-11-18
  • Proteomics by mass spectrometry: approaches, advances, and applications.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2009-04-30
    John R Yates,Cristian I Ruse,Aleksey Nakorchevsky

    Mass spectrometry (MS) is the most comprehensive and versatile tool in large-scale proteomics. In this review, we dissect the overall framework of the MS experiment into its key components. We discuss the fundamentals of proteomic analyses as well as recent developments in the areas of separation methods, instrumentation, and overall experimental design. We highlight both the inherent strengths and limitations of protein MS and offer a rough guide for selecting an experimental design based on the goals of the analysis. We emphasize the versatility of the Orbitrap, a novel mass analyzer that features high resolution (up to 150,000), high mass accuracy (2-5 ppm), a mass-to-charge range of 6000, and a dynamic range greater than 10(3). High mass accuracy of the Orbitrap expands the arsenal of the data acquisition and analysis approaches compared with a low-resolution instrument. We discuss various chromatographic techniques, including multidimensional separation and ultra-performance liquid chromatography. Multidimensional protein identification technology (MudPIT) involves a continuum sample preparation, orthogonal separations, and MS and software solutions. We discuss several aspects of MudPIT applications to quantitative phosphoproteomics. MudPIT application to large-scale analysis of phosphoproteins includes (a) a fractionation procedure for motif-specific enrichment of phosphopeptides, (b) development of informatics tools for interrogation and validation of shotgun phosphopeptide data, and (c) in-depth data analysis for simultaneous determination of protein expression and phosphorylation levels, analog to western blot measurements. We illustrate MudPIT application to quantitative phosphoproteomics of the beta adrenergic pathway. We discuss several biological discoveries made via mass spectrometry pipelines with a focus on cell signaling proteomics.

    更新日期:2019-11-01
  • Synergizing Engineering and Biology to Treat and Model Skeletal Muscle Injury and Disease.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2015-12-09
    Nenad Bursac,Mark Juhas,Thomas A Rando

    Although skeletal muscle is one of the most regenerative organs in our body, various genetic defects, alterations in extrinsic signaling, or substantial tissue damage can impair muscle function and the capacity for self-repair. The diversity and complexity of muscle disorders have attracted much interest from both cell biologists and, more recently, bioengineers, leading to concentrated efforts to better understand muscle pathology and develop more efficient therapies. This review describes the biological underpinnings of muscle development, repair, and disease, and discusses recent bioengineering efforts to design and control myomimetic environments, both to study muscle biology and function and to aid in the development of new drug, cell, and gene therapies for muscle disorders. The synergy between engineering-aided biological discovery and biology-inspired engineering solutions will be the path forward for translating laboratory results into clinical practice.

    更新日期:2019-11-01
  • Mechanics in neuronal development and repair.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2013-05-07
    Kristian Franze,Paul A Janmey,Jochen Guck

    Biological cells are well known to respond to a multitude of chemical signals. In the nervous system, chemical signaling has been shown to be crucially involved in development, normal functioning, and disorders of neurons and glial cells. However, there are an increasing number of studies showing that these cells also respond to mechanical cues. Here, we summarize current knowledge about the mechanical properties of nervous tissue and its building blocks, review recent progress in methodology and understanding of cellular mechanosensitivity in the nervous system, and provide an outlook on the implications of neuromechanics for future developments in biomedical engineering to aid overcoming some of the most devastating and currently incurable CNS pathologies such as spinal cord injuries and multiple sclerosis.

    更新日期:2019-11-01
  • Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2011-03-23
    Stephen F Badylak,Doris Taylor,Korkut Uygun

    The definitive treatment for end-stage organ failure is orthotopic transplantation. However, the demand for transplantation far exceeds the number of available donor organs. A promising tissue-engineering/regenerative-medicine approach for functional organ replacement has emerged in recent years. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. However, significant challenges for three-dimensional organ engineering approach remain. This manuscript describes the fundamental concepts of whole-organ engineering, including characterization of the extracellular matrix as a scaffold, methods for decellularization of vascular organs, potential cells to reseed such a scaffold, techniques for the recellularization process and important aspects regarding bioreactor design to support this approach. Critical challenges and future directions are also discussed.

    更新日期:2019-11-01
  • Design of Catalytic Peptides and Proteins Through Rational and Combinatorial Approaches.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2016-03-30
    Yoshiaki Maeda,Olga V Makhlynets,Hiroshi Matsui,Ivan V Korendovych

    This review focuses on recent progress in noncomputational methods to introduce catalytic function into proteins, peptides, and peptide assemblies. We discuss various approaches to creating catalytic activity and classification of noncomputational methods into rational and combinatorial classes. The section on rational design covers recent progress in the development of short peptides and oligomeric peptide assemblies for various natural and unnatural reactions. The section on combinatorial design describes recent advances in the discovery of catalytic peptides. We present the future prospects of these and other new approaches in a broader context, including implications for functional material design.

    更新日期:2019-11-01
  • Emerging Themes in Image Informatics and Molecular Analysis for Digital Pathology.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2016-07-16
    Rohit Bhargava,Anant Madabhushi

    Pathology is essential for research in disease and development, as well as for clinical decision making. For more than 100 years, pathology practice has involved analyzing images of stained, thin tissue sections by a trained human using an optical microscope. Technological advances are now driving major changes in this paradigm toward digital pathology (DP). The digital transformation of pathology goes beyond recording, archiving, and retrieving images, providing new computational tools to inform better decision making for precision medicine. First, we discuss some emerging innovations in both computational image analytics and imaging instrumentation in DP. Second, we discuss molecular contrast in pathology. Molecular DP has traditionally been an extension of pathology with molecularly specific dyes. Label-free, spectroscopic images are rapidly emerging as another important information source, and we describe the benefits and potential of this evolution. Third, we describe multimodal DP, which is enabled by computational algorithms and combines the best characteristics of structural and molecular pathology. Finally, we provide examples of application areas in telepathology, education, and precision medicine. We conclude by discussing challenges and emerging opportunities in this area.

    更新日期:2019-11-01
  • Engineered Models of Confined Cell Migration.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2016-07-16
    Colin D Paul,Wei-Chien Hung,Denis Wirtz,Konstantinos Konstantopoulos

    Cells in the body are physically confined by neighboring cells, tissues, and the extracellular matrix. Although physical confinement modulates intracellular signaling and the underlying mechanisms of cell migration, it is difficult to study in vivo. Furthermore, traditional two-dimensional cell migration assays do not recapitulate the complex topographies found in the body. Therefore, a number of experimental in vitro models that confine and impose forces on cells in well-defined microenvironments have been engineered. We describe the design and use of microfluidic microchannel devices, grooved substrates, micropatterned lines, vertical confinement devices, patterned hydrogels, and micropipette aspiration assays for studying cell responses to confinement. Use of these devices has enabled the delineation of changes in cytoskeletal reorganization, cell-substrate adhesions, intracellular signaling, nuclear shape, and gene expression that result from physical confinement. These assays and the physiologically relevant signaling pathways that have been elucidated are beginning to have a translational and clinical impact.

    更新日期:2019-11-01
  • Chemical exchange saturation transfer contrast agents for magnetic resonance imaging.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2008-07-24
    A Dean Sherry,Mark Woods

    Magnetic resonance imaging (MRI) contrast agents have become an important tool in clinical medicine. The most common agents are Gd(3+)-based complexes that shorten bulk water T(1) by rapid exchange of a single inner-sphere water molecule with bulk solvent water. Current gadolinium agents lack tissue specificity and typically do not respond to their chemical environment. Recently, it has been demonstrated that MR contrast may be altered by an entirely different mechanism based on chemical exchange saturation transfer (CEST). CEST contrast can originate from exchange of endogenous amide or hydroxyl protons or from exchangeable sites on exogenous CEST agents. This has opened the door for the discovery of new classes of responsive agents ranging from MR gene reporter molecules to small molecules that sense their tissue environment and respond to biological events.

    更新日期:2019-11-01
  • Living-cell microarrays.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2009-05-06
    Martin L Yarmush,Kevin R King

    Living cells are remarkably complex. To unravel this complexity, living-cell assays have been developed that allow delivery of experimental stimuli and measurement of the resulting cellular responses. High-throughput adaptations of these assays, known as living-cell microarrays, which are based on microtiter plates, high-density spotting, microfabrication, and microfluidics technologies, are being developed for two general applications: (a) to screen large-scale chemical and genomic libraries and (b) to systematically investigate the local cellular microenvironment. These emerging experimental platforms offer exciting opportunities to rapidly identify genetic determinants of disease, to discover modulators of cellular function, and to probe the complex and dynamic relationships between cells and their local environment.

    更新日期:2019-11-01
  • Multiscale computational models of complex biological systems.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2013-05-07
    Joseph Walpole,Jason A Papin,Shayn M Peirce

    Integration of data across spatial, temporal, and functional scales is a primary focus of biomedical engineering efforts. The advent of powerful computing platforms, coupled with quantitative data from high-throughput experimental methodologies, has allowed multiscale modeling to expand as a means to more comprehensively investigate biological phenomena in experimentally relevant ways. This review aims to highlight recently published multiscale models of biological systems, using their successes to propose the best practices for future model development. We demonstrate that coupling continuous and discrete systems best captures biological information across spatial scales by selecting modeling techniques that are suited to the task. Further, we suggest how to leverage these multiscale models to gain insight into biological systems using quantitative biomedical engineering methods to analyze data in nonintuitive ways. These topics are discussed with a focus on the future of the field, current challenges encountered, and opportunities yet to be realized.

    更新日期:2019-11-01
  • Mechanical regulation of nuclear structure and function.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2012-06-05
    Rui P Martins,John D Finan,Farshid Guilak,David A Lee

    Mechanical loading induces both nuclear distortion and alterations in gene expression in a variety of cell types. Mechanotransduction is the process by which extracellular mechanical forces can activate a number of well-studied cytoplasmic signaling cascades. Inevitably, such signals are transduced to the nucleus and induce transcription factor-mediated changes in gene expression. However, gene expression also can be regulated through alterations in nuclear architecture, providing direct control of genome function. One putative transduction mechanism for this phenomenon involves alterations in nuclear architecture that result from the mechanical perturbation of the cell. This perturbation is associated with direct mechanical strain or osmotic stress, which is transferred to the nucleus. This review describes the current state of knowledge relating the nuclear architecture and the transfer of mechanical forces to the nucleus mediated by the cytoskeleton, the nucleoskeleton, and the LINC (linker of the nucleoskeleton and cytoskeleton) complex. Moreover, remodeling of the nucleus induces alterations in nuclear stiffness, which may be associated with cell differentiation. These phenomena are discussed in relation to the potential influence of nuclear architecture-mediated mechanoregulation of transcription and cell fate.

    更新日期:2019-11-01
  • Robotics, motor learning, and neurologic recovery.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2004-07-17
    David J Reinkensmeyer,Jeremy L Emken,Steven C Cramer

    Robotic devices are helping shed light on human motor control in health and injury. By using robots to apply novel force fields to the arm, investigators are gaining insight into how the nervous system models its external dynamic environment. The nervous system builds internal models gradually by experience and uses them in combination with impedance and feedback control strategies. Internal models are robust to environmental and neural noise, generalized across space, implemented in multiple brain regions, and developed in childhood. Robots are also being used to assist in repetitive movement practice following neurologic injury, providing insight into movement recovery. Robots can haptically assess sensorimotor performance, administer training, quantify amount of training, and improve motor recovery. In addition to providing insight into motor control, robotic paradigms may eventually enhance motor learning and rehabilitation beyond the levels possible with conventional training techniques.

    更新日期:2019-11-01
  • Advances in quantitative electroencephalogram analysis methods.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2004-07-17
    Nitish V Thakor,Shanbao Tong

    Quantitative electroencephalogram (qEEG) plays a significant role in EEG-based clinical diagnosis and studies of brain function. In past decades, various qEEG methods have been extensively studied. This article provides a detailed review of the advances in this field. qEEG methods are generally classified into linear and nonlinear approaches. The traditional qEEG approach is based on spectrum analysis, which hypothesizes that the EEG is a stationary process. EEG signals are nonstationary and nonlinear, especially in some pathological conditions. Various time-frequency representations and time-dependent measures have been proposed to address those transient and irregular events in EEG. With regard to the nonlinearity of EEG, higher order statistics and chaotic measures have been put forward. In characterizing the interactions across the cerebral cortex, an information theory-based measure such as mutual information is applied. To improve the spatial resolution, qEEG analysis has also been combined with medical imaging technology (e.g., CT, MR, and PET). With these advances, qEEG plays a very important role in basic research and clinical studies of brain injury, neurological disorders, epilepsy, sleep studies and consciousness, and brain function.

    更新日期:2019-11-01
  • Fractal analysis of the vascular tree in the human retina.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2004-07-17
    Barry R Masters

    The retinal circulation of the normal human retinal vasculature is statistically self-similar and fractal. Studies from several groups present strong evidence that the fractal dimension of the blood vessels in the normal human retina is approximately 1.7. This is the same fractal dimension that is found for a diffusion-limited growth process, and it may have implications for the embryological development of the retinal vascular system. The methods of determining the fractal dimension for branching trees are reviewed together with proposed models for the optimal formation (Murray Principle) of the branching vascular tree in the human retina and the branching pattern of the human bronchial tree. The limitations of fractal analysis of branching biological structures are evaluated. Understanding the design principles of branching vascular systems and the human bronchial tree may find applications in tissue and organ engineering, i.e., bioartificial organs for both liver and kidney.

    更新日期:2019-11-01
  • Engineering synthetic vectors for improved DNA delivery: insights from intracellular pathways.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2004-07-17
    Charles M Roth,Sumati Sundaram

    Significant progress has been made in the area of nonviral gene delivery to date. Yet, synthetic vectors remain less efficient by orders of magnitude than their viral counterparts. Research continues toward unraveling and overcoming various barriers to the efficient delivery of DNA, whether in plasmid form encoding a gene or as an oligonucleotide for the selective inhibition of target gene expression. Novel components for overcoming these hurdles are continually being incorporated into the design of synthetic vectors, leading to increasingly more virus-like particles. Despite these advances, general principles defining the design of synthetic vectors are yet to be developed fully. A more quantitative analysis of the cellular uptake and intracellular processing of these vectors is required for the rational manipulation of vector design. Mathematical frameworks with a more conceptual basis will help obtain an integrated perspective on these complex systems. In this review, we critically examine the progress made toward the improved design of synthetic vectors by the strategic exploitation of intracellular mechanisms and explore newer possibilities to overcome obstacles in the practical realization of this field.

    更新日期:2019-11-01
  • Molecular machines.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2004-07-17
    C Mavroidis,A Dubey,M L Yarmush

    Molecular machines are tiny energy conversion devices on the molecular-size scale. Whether naturally occurring or synthetic, these machines are generally more efficient than their macroscale counterparts. They have their own mechanochemistry, dynamics, workspace, and usability and are composed of nature's building blocks: namely proteins, DNA, and other compounds, built atom by atom. With modern scientific capabilities it has become possible to create synthetic molecular devices and interface them with each other. Countless such machines exist in nature, and it is possible to build artificial ones by mimicking nature. Here we review some of the known molecular machines, their structures, features, and characteristics. We also look at certain devices in their early development stages, as well as their future applications and challenges.

    更新日期:2019-11-01
  • Fluid mechanics of heart valves.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2004-07-17
    Ajit P Yoganathan,Zhaoming He,S Casey Jones

    Valvular heart disease is a life-threatening disease that afflicts millions of people worldwide and leads to approximately 250,000 valve repairs and/or replacements each year. Malfunction of a native valve impairs its efficient fluid mechanic/hemodynamic performance. Artificial heart valves have been used since 1960 to replace diseased native valves and have saved millions of lives. Unfortunately, despite four decades of use, these devices are less than ideal and lead to many complications. Many of these complications/problems are directly related to the fluid mechanics associated with the various mechanical and bioprosthetic valve designs. This review focuses on the state-of-the-art experimental and computational fluid mechanics of native and prosthetic heart valves in current clinical use. The fluid dynamic performance characteristics of caged-ball, tilting-disc, bileaflet mechanical valves and porcine and pericardial stented and nonstented bioprostheic valves are reviewed. Other issues related to heart valve performance, such as biomaterials, solid mechanics, tissue mechanics, and durability, are not addressed in this review.

    更新日期:2019-11-01
  • Functional efficacy of tendon repair processes.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2004-07-17
    David L Butler,Natalia Juncosa,Matthew R Dressler

    Despite various attempts to repair and replace injured tendon, an understanding of the repair processes and a systematic approach to achieving functional efficacy remain elusive. In this review the epidemiology of tendon injury and repair is first examined. Using a traditional paradigm for repair assessment, the biology and biomechanics of normal tendon, natural healing, and repair are then explored. New treatment strategies such as functional tissue engineering are discussed, including a functional approach to treatment that involves the development of in vivo functional design parameters to judge the acceptability of a repair outcome. The paper concludes with future directions.

    更新日期:2019-11-01
  • Mechanotransduction at cell-matrix and cell-cell contacts.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2004-07-17
    Christopher S Chen,John Tan,Joe Tien

    Mechanical forces play an important role in the organization, growth, maturation, and function of living tissues. At the cellular level, many of the biological responses to external forces originate at two types of specialized microscale structures: focal adhesions that link cells to their surrounding extracellular matrix and adherens junctions that link adjacent cells. Transmission of forces from outside the cell through cell-matrix and cell-cell contacts appears to control the maturation or disassembly of these adhesions and initiates intracellular signaling cascades that ultimately alter many cellular behaviors. In response to externally applied forces, cells actively rearrange the organization and contractile activity of the cytoskeleton and redistribute their intracellular forces. Recent studies suggest that the localized concentration of these cytoskeletal tensions at adhesions is also a major mediator of mechanical signaling. This review summarizes the role of mechanical forces in the formation, stabilization, and dissociation of focal adhesions and adherens junctions and outlines how integration of signals from these adhesions over the entire cell body affects how a cell responds to its mechanical environment. This review also describes advanced optical, lithographic, and computational techniques for the study of mechanotransduction.

    更新日期:2019-11-01
  • Ocular biomechanics and biotransport.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2004-07-17
    C Ross Ethier,Mark Johnson,Jeff Ruberti

    The eye transduces light, and we usually do not think of it as a biomechanical structure. Yet it is actually a pressurized, thick-walled shell that has an internal and external musculature, a remarkably complex internal vascular system, dedicated fluid production and drainage tissues, and a variety of specialized fluid and solute transport systems. Biomechanics is particularly involved in accommodation (focusing near and far), as well as in common disorders such as glaucoma, macular degeneration, myopia, and presbyopia. In this review, we give a (necessarily brief) overview of many of the interesting biomechanical aspects of the eye, concluding with a list of open problems.

    更新日期:2019-11-01
  • Mechanical bioeffects of ultrasound.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2004-07-17
    Diane Dalecki

    Ultrasound is used widely in medicine as both a diagnostic and therapeutic tool. Through both thermal and nonthermal mechanisms, ultrasound can produce a variety of biological effects in tissues in vitro and in vivo. This chapter provides an overview of the fundamentals of key nonthermal mechanisms for the interaction of ultrasound with biological tissues. Several categories of mechanical bioeffects of ultrasound are then reviewed to provide insight on the range of ultrasound bioeffects in vivo, the relevance of these effects to diagnostic imaging, and the potential application of mechanical bioeffects to the design of new therapeutic applications of ultrasound in medicine.

    更新日期:2019-11-01
  • Optical projection tomography.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2004-07-17
    James Sharpe

    Optical projection tomography is a new approach for three-dimensional (3-D) imaging of small biological specimens. It fills an imaging gap between MRI and confocal microscopy, being most suited to specimens that are from 1 to 10 mm across. The tomographic principles of optical projection tomography (OPT) are explained, its most important applications in biomedical research explored, and comparisons drawn of its pros and cons compared to a number of alternative imaging technologies.

    更新日期:2019-11-01
  • Micro-computed tomography-current status and developments.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2004-07-17
    Erik L Ritman

    The recent rapid increase in interest in tomographic imaging of small animals and of human (and large animal) organ biopsies is driven largely by drug discovery, cancer detection/monitoring, phenotype identification and/or characterization, and development of disease detection methods and monitoring efficacies of drugs in disease treatment. In biomedical applications, micro-computed tomography (CT) scanners can function as scaled-down (i.e., mini) clinical CT scanners that provide a three-dimensional (3-D) image of most, if not the entire, torso of a mouse at image resolution (50-100 microm) scaled proportional to that of a human CT image. Micro-CT scanners, on the other hand, image specimens the size of intact rodent organs at spatial resolutions from cellular (20 microm) down to subcellular dimensions (e.g., 1 microm) and fill the resolution-hiatus between microscope imaging, which resolves individual cells in thin sections of tissue, and mini-CT imaging of intact volumes.

    更新日期:2019-11-01
  • Advances in high-field magnetic resonance imaging.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2004-07-17
    Xiaoping Hu,David G Norris

    Among advances in magnetic resonance imaging (MRI), the increase of the magnetic field strength is perhaps one of the most significant. The use of high magnetic fields for in vivo magnetic resonance is motivated by a number of considerations. Advantages are increases in signal-to-noise ratio, blood-oxygenation level-dependent contrast, and spectral resolution, while disadvantages include potential reduction of contrast in anatomic imaging owing to lengthening of T1 and effects of susceptibility of high fields. To address these challenges, technical advances have been made in various aspects of MRI, allowing high-field MRI to provide exquisite morphological and functional details in clinical and research settings. This review provides an overview of technical issues and applications of high-field MRI.

    更新日期:2019-11-01
  • Tissue engineering of ligaments.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2004-07-17
    G Vunjak-Novakovic,Gregory Altman,Rebecca Horan,David L Kaplan

    Tissue engineering is emerging as a significant clinical option to address tissue and organ failure by implanting biological substitutes for the compromised tissues. As compared to the transplantation of cells alone, engineered tissues offer the potential advantage of immediate functionality. Engineered tissues can also serve as physiologically relevant models for controlled studies of cells and tissues designed to distinguish the effects of specific signals from the complex milieu of factors present in vivo. A high number of ligament failures and the lack of adequate options to fully restore joint functions have prompted the need to develop new tissue engineering strategies. We discuss the requirements for ligament reconstruction, the available treatment options and their limitations, and then focus on the tissue engineering of ligaments. One representative tissue engineering system involving the integrated use of adult human stem cells, custom-designed scaffolds, and advanced bioreactors with dynamic loading is described.

    更新日期:2019-11-01
  • Breast tissue engineering.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2004-07-17
    Charles W Patrick

    Tissue engineering has the potential to redefine rehabilitation for the breast cancer patient by providing a translatable strategy that restores the postmastectomy breast mound while concomitantly obviating limitations realized with contemporary reconstructive surgery procedures. The engineering design goal is to provide a sufficient volume of viable fat tissue based on a patient's own cells such that deficits in breast volume can be abrogated. To be sure, adipose tissue engineering is in its infancy, but tremendous strides have been made. Numerous studies attest to the feasibility of adipose tissue engineering. The field is now poised to challenge barriers to clinical translation that are germane to most tissue engineering applications, namely scale-up, large animal model development, and vascularization. The innovative and rapid progress of adipose engineering to date, as well as opportunities for its future growth, is presented.

    更新日期:2019-11-01
  • Tissue growth and remodeling.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2004-07-17
    Stephen C Cowin

    The growth and remodeling of a tissue depends on certain features in the history of its mechanical environment as well as its genetic makeup. The mechanical environment influences the tissue's developing morphology, the process of simply increasing the size of existing morphological structures, and the formation of the proteins of which the tissue is constructed. The relationships between genetic information, various epigenetic mechanisms and tissue development are discussed. The developmental growth and remodeling of most structural tissues are enhanced by the use of those tissues and retarded by their disuse. The mechanical or mathematical modeling of tissue growth and development using cellular automata models and continuum mechanical models is reviewed.

    更新日期:2019-11-01
  • Biomaterials: where we have been and where we are going.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2004-07-17
    Buddy D Ratner,Stephanie J Bryant

    Since its inception just over a half century ago, the field of biomaterials has seen a consistent growth with a steady introduction of new ideas and productive branches. This review describes where we have been, the state of the art today, and where we might be in 10 or 20 years. Herein, we highlight some of the latest advancements in biomaterials that aim to control biological responses and ultimately heal. This new generation of biomaterials includes surface modification of materials to overcome nonspecific protein adsorption in vivo, precision immobilization of signaling groups on surfaces, development of synthetic materials with controlled properties for drug and cell carriers, biologically inspired materials that mimic natural processes, and design of sophisticated three-dimensional (3-D) architectures to produce well-defined patterns for diagnostics, e.g., biological microelectromechanical systems (bioMEMs), and tissue engineering.

    更新日期:2019-11-01
  • Tissue engineering applications of therapeutic cloning.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2004-07-17
    Anthony Atala,Chester J Koh

    Few treatment options are available for patients suffering from diseased and injured organs because of a severe shortage of donor organs available for transplantation. Therapeutic cloning, where the nucleus from a donor cell is transferred into an enucleated oocyte in order to extract pluripotent embryonic stem cells, offers a potentially limitless source of cells for replacement therapy. Scientists in the field of tissue engineering apply the principles of cell transplantation, material science, and engineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. The present chapter reviews recent advances that have occurred in therapeutic cloning and tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure.

    更新日期:2019-11-01
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  • The tissue engineeting puzzle: a molecular perspective.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2003-10-07
    Viola Vogel,Gretchen Baneyx

    The inability of biomaterial scaffolds to functionally integrate into surrounding tissue is one of the major roadblocks to developing new biomaterials and tissue-engineering scaffolds. Despite considerable advances, current approaches to engineering cell-surface interactions fall short in mimicking the complexity of signals through which surrounding tissue regulates cell behavior. Cells adhere and interact with their extracellular environment via integrins, and their ability to activate associated downstream signaling pathways depends on the character of adhesion complexes formed between cells and their extracellular matrix. In particular, alpha5beta1 and alphavbeta3 integrins are central to regulating downstream events, including cell survival and cell-cycle progression. In contrast to previous findings that alphavbeta3 integrins promote angiogenesis, recent evidence argues that alphavbeta3 integrins may act as negative regulators of proangiogenic integrins such as alpha5beta1. This suggests that fibronectin is critical for scaffold vascularization because it is the only mammalian adhesion protein that binds and activates alpha5beta1 integrins. Cells are furthermore capable of stretching fibronectin matrices such that the protein partially unfolds, and recent computational simulations provide structural models of how mechanical stretching affects fibronectin function. We propose a model whereby excessive tension generated by cells in contact to biomaterials may in fact render fibronectin fibrils nonangiogenic and potentially inhibit vascularization. The model could explain why current biomaterials independent of their surface chemistries and textures fail to vascularize.

    更新日期:2019-11-01
  • Time-reversal acoustics in biomedical engineering.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2003-10-07
    Mathias Fink,Gabriel Montaldo,Mickael Tanter

    Time reversal is a very powerful method for focusing through complex and heterogeneous media and shows very promising results in biomedical applications. In this paper, we review some of the main applications investigated during the past decade. An iterative implementation of the time-reversal process allows tracking gallstones in real time during lithotripsy treatments. In this application domain, a smart exploitation of the reverberations in solid waveguides permits the focusing of high-amplitude ultrasonic shock waves with a small number of transducers. Finally, because time reversal is able to correct the strong distortions induced by the skull bone on ultrasonic propagation, this adaptive focusing technique is very promising for ultrasonic hyperthermia brain therapy.

    更新日期:2019-11-01
  • Biomonitoring with wireless communications.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2003-10-07
    Thomas F Budinger

    Wireless biomonitoring, first used in human beings for fetal heart-rate monitoring more than 30 years ago, has now become a technology for remote sensing of patients' activity, blood pulse pressure, oxygen saturation, internal pressures, orthopedic device loading, and gastrointestinal endoscopy. Technical advances in miniaturization and wireless communications have enabled development of monitoring devices that can be made available for general use by individuals/patients and caregivers. New methods for short-range wireless communications not encumbered by radio spectrum restrictions (e.g., ultra-wideband) will enable applications of wireless monitoring without interference in ambulatory subjects, in home care, and in hospitals.

    更新日期:2019-11-01
  • Metabolic engineering: advances in modeling and intervention in health and disease.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2003-10-07
    Martin L Yarmush,Scott Banta

    The field of metabolic engineering encompasses a powerful set of tools that can be divided into (a) methods to model complex metabolic pathways and (b) techniques to manipulate these pathways for a desired metabolic outcome. These tools have recently seen increased utility in the medical arena, and this paper aims to review significant accomplishments made using these approaches. The modeling of metabolic pathways has been applied to better understand disease-state physiology in a variety of cellar, subcellular, and organ systems, including the liver, heart, mitochondria, and cancerous cells. Metabolic pathway engineering has been used to generate cells with novel biochemical functions for therapeutic use, and specific examples are provided in the areas of glycosylation engineering and dopamine-replacement therapy. In order to document the potential of applying both metabolic modeling and pathway manipulation, we describe pertinent advances in the field of diabetes research. Undoubtedly, as the field of metabolic engineering matures and is applied to a wider array of problems, new advances and therapeutic strategies will follow.

    更新日期:2019-11-01
  • Neural tissue engineering: strategies for repair and regeneration.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2003-10-07
    Christine E Schmidt,Jennie Baier Leach

    Nerve regeneration is a complex biological phenomenon. In the peripheral nervous system, nerves can regenerate on their own if injuries are small. Larger injuries must be surgically treated, typically with nerve grafts harvested from elsewhere in the body. Spinal cord injury is more complicated, as there are factors in the body that inhibit repair. Unfortunately, a solution to completely repair spinal cord injury has not been found. Thus, bioengineering strategies for the peripheral nervous system are focused on alternatives to the nerve graft, whereas efforts for spinal cord injury are focused on creating a permissive environment for regeneration. Fortunately, recent advances in neuroscience, cell culture, genetic techniques, and biomaterials provide optimism for new treatments for nerve injuries. This article reviews the nervous system physiology, the factors that are critical for nerve repair, and the current approaches that are being explored to aid peripheral nerve regeneration and spinal cord repair.

    更新日期:2019-11-01
  • Engineered nanomaterials for biophotonics applications: improving sensing, imaging, and therapeutics.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2003-10-07
    Jennifer L West,Naomi J Halas

    Advances in chemistry and physics are providing an expanding array of nanostructured materials with unique and powerful optical properties. These nanomaterials provide a new set of tools that are available to biomedical engineers, biologists, and medical scientists who seek new tools as biosensors and probes of biological fluids, cells, and tissue chemistry and function. Nanomaterials are also being used to develop optically controlled devices for applications such as modulated drug delivery as well as optical therapeutics. This review discusses applications that have been successfully demonstrated using nanomaterials including semiconductor nanocrystals, gold nanoparticles, gold nanoshells, and silver plasmon resonant particles.

    更新日期:2019-11-01
  • The engineering of gene regulatory networks.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2003-10-07
    Mads Kaern,William J Blake,J J Collins

    The rapid accumulation of genetic information and advancement of experimental techniques have opened a new frontier in biomedical engineering. With the availability of well-characterized components from natural gene networks, the stage has been set for the engineering of artificial gene regulatory networks with sophisticated computational and functional capabilities. In these efforts, the ability to construct, analyze, and interpret qualitative and quantitative models is becoming increasingly important. In this review, we consider the current state of gene network engineering from a combined experimental and modeling perspective. We discuss how networks with increased complexity are being constructed from simple modular components and how quantitative deterministic and stochastic modeling of these modules may provide the foundation for accurate in silico representations of gene regulatory network function in vivo.

    更新日期:2019-11-01
  • Modeling total heart function.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2003-10-07
    Peter J Hunter,Andrew J Pullan,Bruce H Smaill

    Computational models of the electrical and mechanical function of the heart are reviewed. These models attempt to explain the integrated function of the heart in terms of ventricular anatomy, the structure and material properties of myocardial tissue, the membrane ion channels, and calcium handling and myofilament mechanics of cardiac myocytes. The models have established the computational framework for linking the structure and function of cardiac cells and tissue to the integrated behavior of the intact heart, but many more aspects of physiological function, including metabolic and signal transduction pathways, need to be included before significant progress can be made in understanding many disease processes.

    更新日期:2019-11-01
  • Temporal dynamics of brain anatomy.
    Annu. Rev. Biomed. Eng. (IF 12.257) Pub Date : 2003-10-07
    Arthur W Toga,Paul M Thompson

    The brain changes profoundly in structure and function during development and as a result of diseases such as the dementias, schizophrenia, multiple sclerosis, and tumor growth. Strategies to measure, map, and visualize these brain changes are of immense value in basic and clinical neuroscience. Algorithms that map brain change with sufficient spatial and temporal sensitivity can also assess drugs that aim to decelerate or arrest these changes. In neuroscience studies, these tools can reveal subtle brain changes in adolescence and old age and link these changes with measurable differences in brain function and cognition. Early detection of brain change in patients at risk for dementia; tumor recurrence; or relapsing-remitting conditions, such as multiple sclerosis, is also vital for optimizing therapy. We review a variety of mathematical and computational approaches to detect structural brain change with unprecedented sensitivity, both spatially and temporally. The resulting four-dimensional (4-D) maps of brain anatomy are warehoused in population-based brain atlases. Here, statistical tools compare brain changes across subjects and across populations, adjusting for complex differences in brain structure. Brain changes in an individual can be compared with a normative database comprised of subjects matched for age, gender, and other demographic factors. These dynamic brain maps offer key biological markers for understanding disease progression and testing therapeutic response. The early detection of disease-related brain changes is also critical for possible pre-emptive intervention before the ravages of disease have set in.

    更新日期:2019-11-01
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