Annual Review of Biomedical Engineering最新文献

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.

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.

Brain activity and connectivity are distributed in the three-dimensional space and evolve in time. It is important to image brain dynamics with high spatial and temporal resolution. Electroencephalography (EEG) and magnetoencephalography (MEG) are noninvasive measurements associated with complex neural activations and interactions that encode brain functions. Electrophysiological source imaging estimates the underlying brain electrical sources from EEG and MEG measurements. It offers increasingly improved spatial resolution and intrinsically high temporal resolution for imaging large-scale brain activity and connectivity on a wide range of timescales. Integration of electrophysiological source imaging and functional magnetic resonance imaging could further enhance spatiotemporal resolution and specificity to an extent that is not attainable with either technique alone. We review methodological developments in electrophysiological source imaging over the past three decades and envision its future advancement into a powerful functional neuroimaging technology for basic and clinical neuroscience applications.

The development processes of arteries and veins are fundamentally different, leading to distinct differences in anatomy, structure, and function as well as molecular profiles. Understanding the complex interaction between genetic and epigenetic pathways, as well as extracellular and biomechanical signals that orchestrate arterial venous differentiation, is not only critical for the understanding of vascular diseases of arteries and veins but also valuable for vascular tissue engineering strategies. Recent research has suggested that certain transcriptional factors not only control arterial venous differentiation during development but also play a critical role in adult vessel function and disease processes. This review summarizes the signaling pathways and critical transcription factors that are important for arterial versus venous specification. We focus on those signals that have a direct relation to the structure and function of arteries and veins, and have implications for vascular disease processes and tissue engineering applications.

As minimally invasive surgical techniques progress, the demand for efficient, reliable methods for vascular ligation and tissue closure becomes pronounced. The surgical advantages of energy-based vessel sealing exceed those of traditional, compression-based ligatures in procedures sensitive to duration, foreign bodies, and recovery time alike. Although the use of energy-based devices to seal or transect vasculature and connective tissue bundles is widespread, the breadth of heating strategies and energy dosimetry used across devices underscores an uncertainty as to the molecular nature of the sealing mechanism and induced tissue effect. Furthermore, energy-based techniques exhibit promise for the closure and functional repair of soft and connective tissues in the nervous, enteral, and dermal tissue domains. A constitutive theory of molecular bonding forces that arise in response to supraphysiological temperatures is required in order to optimize and progress the use of energy-based tissue fusion. While rapid tissue bonding has been suggested to arise from dehydration, dipole interactions, molecular cross-links, or the coagulation of cellular proteins, long-term functional tissue repair across fusion boundaries requires that the reaction to thermal damage be tailored to catalyze the onset of biological healing and remodeling. In this review, we compile and contrast findings from published thermal fusion research in an effort to encourage a molecular approach to characterization of the prevalent and promising energy-based tissue bond.

This review explores bioheat transfer applications at multiple scales from nanoparticle (NP) heating to whole-body thermoregulation. For instance, iron oxide nanoparticles are being used for nanowarming, which uniformly and quickly rewarms 50-80-mL (≤5-cm-diameter) vitrified systems by coupling with radio-frequency (RF) fields where standard convective warming fails. A modification of this approach can also be used to successfully rewarm cryopreserved fish embryos (∼0.8 mm diameter) by heating previously injected gold nanoparticles with millisecond pulsed laser irradiation where standard convective warming fails. Finally, laser-induced heating of gold nanoparticles can improve the sensitivity of lateral flow assays (LFAs) so that they are competitive with laboratory tests such as the enzyme-linked immunosorbent assay. This approach addresses the main weakness of LFAs, which are otherwise the cheapest, easiest, and fastest to use point-of-care diagnostic tests in the world. Body core temperature manipulation has now become possible through selective thermal stimulation (STS) approaches. For instance, simple and safe heating of selected areas of the skin surface can open arteriovenous anastomosis flow in glabrous skin when it is not already established, thereby creating a convenient and effective pathway to induce heat flow between the body core and environment. This has led to new applications of STS to increase or decrease core temperatures in humans and animals to assist in surgery (perioperative warming), to aid ischemic stress recovery (cooling), and even to enhance the quality of sleep. Together, these multiscale applications of nanoparticle heating and thermoregulation point to dramatic opportunities for translation and impact in these prophylactic, preservative, diagnostic, and therapeutic applications of bioheat transfer.

Mucus selectively controls the transport of molecules, particulate matter, and microorganisms to the underlying epithelial layer. It may be desirable to weaken the mucus barrier to enable effective delivery of drug carriers. Alternatively, the mucus barrier can be strengthened to prevent epithelial interaction with pathogenic microbes or other exogenous materials. The dynamic mucus layer can undergo changes in structure (e.g., pore size) and/or composition (e.g., protein concentrations, mucin glycosylation) in response to stimuli that occur naturally or are purposely administered, thus altering its barrier function. This review outlines mechanisms by which mucus provides a selective barrier and methods to engineer the mucus layer from the perspective of strengthening or weakening its barrier properties. In addition, we discuss strategic design of drug carriers and dosing formulation properties for efficient delivery across the mucus barrier.

Cellular immunotherapy holds great promise for the treatment of human disease. Clinical evidence suggests that T cell immunotherapies have the potential to combat cancers that evade traditional immunotherapy. Despite promising results, adverse effects leading to fatalities have left scientists seeking tighter control over these therapies, which is reflected in the growing body of synthetic biology literature focused on developing tightly controlled, context-independent parts. In addition, researchers are adapting these tools for other uses, such as for the treatment of autoimmune disease, HIV infection, and fungal interactions. We review this body of work and devote special attention to approaches that may lend themselves to the development of an "ideal" therapy: one that is safe, efficient, and easy to manufacture. We conclude with a look toward the future of immunotherapy: how synthetic biology can shift the paradigm from the treatment of disease to a focus on wellness and human health as a whole.

Inorganic nanomaterials have witnessed significant advances in areas of medicine including cancer therapy, imaging, and drug delivery, but their use in soft tissue repair and regeneration is in its infancy. Metallic, ceramic, and carbon allotrope nanoparticles have shown promise in facilitating tissue repair and regeneration. Inorganic nanomaterials have been employed to improve stem cell engraftment in cellular therapy, material mechanical stability in tissue repair, electrical conductivity in nerve and cardiac regeneration, adhesion strength in tissue approximation, and antibacterial capacity in wound dressings. These nanomaterials have also been used to improve or replace common surgical materials and restore functionality to damaged tissue. We provide a comprehensive overview of inorganic nanomaterials in tissue repair and regeneration, and discuss their promise and limitations for eventual translation to the clinic.

The zygapophysial joint, a diarthrodial joint commonly referred to as the facet joint, plays a pivotal role in back pain, a condition that has been a leading cause of global disability since 1990. Along with the intervertebral disc, the facet joint supports spinal motion and aids in spinal stability. Highly susceptible to early development of osteoarthritis, the facet is responsible for a significant amount of pain in the low-back, mid-back, and neck regions. Current noninvasive treatments cannot offer long-term pain relief, while invasive treatments can relieve pain but fail to preserve joint functionality. This review presents an overview of the facet in terms of its anatomy, functional properties, problems, and current management strategies. Furthermore, this review introduces the potential for regeneration of the facet and particular engineering strategies that could be employed as a long-term treatment.