Critical Reviews in Biomedical Engineering最新文献

At the nanoscale, pushing, pulling, and shearing forces drive biochemical processes in development and remodeling as well as in wound healing and disease progression. Research in the field of mechanobiology investigates not only how these loads affect biochemical signaling pathways but also how signaling pathways respond to local loading by triggering mechanical changes such as regional stiffening of a tissue. This feedback between mechanical and biochemical signaling is increasingly recognized as fundamental in embryonic development, tissue morphogenesis, cell signaling, and disease pathogenesis. Historically, the interdisciplinary field of mechanobiology has been driven by the development of technologies for measuring and manipulating cellular and molecular forces, with each new tool enabling vast new lines of inquiry. In this review, we discuss recent advances in the manufacturing and capabilities of molecular-scale force and strain sensors. We also demonstrate how DNA nanotechnology has been critical to the enhancement of existing techniques and to the development of unique capabilities for future mechanosensor assembly. DNA is a responsive and programmable building material for sensor fabrication. It enables the systematic interrogation of molecular biomechanics with forces at the 1- to 200-pN scale that are needed to elucidate the fundamental means by which cells and proteins transduce mechanical signals.

Noncontact lower extremity injuries are commonly related to jumping and landing activities. This review presents an overview of relevant biomechanical variables that can be modified in training to improve jumping performance, landing mechanics, and consequently, reduce injury risks. Relevant studies from the last 2 decades in the Compendex, Pubmed, and Scopus databases were considered for this review. Studies related to jumping and landing kinetics, kinematics, injuries, performance, and/or simulation were included. The use of experimental methods as the drop jump landing and jumping countermovement are widely used to measure biomechanical variables. At the same time, there has been a continuous development of simulation models that could present results without the need for testing on human subjects, with the final objective of exploring the limits of an athlete's performance without increasing the risk of any injury. The most common injuries occur in the knee and ankle ligaments and are directly related to joint angles and moments (i.e., torque or joint loading) at the hip, ankle, and knee joints. Jumping and landing biomechanics are considerably different between male and female subjects for different experimental methods and in both cases, these kinematics factors can be improved over shorter- or longer-time training to develop a better landing strategy.

Clustered regularly interspaced palindromic repeats (CRISPR) technique plays a vital role in preclinical modelling of many respiratory diseases. Diseases such as chronic obstructive pulmonary disease (COPD), asthma, acute tracheal bronchitis, pneumonia, tuberculosis, lung cancer, and influenza infection continue to significantly impact human health. CRISPR associated (Cas) proteins, isolated from the immune system of prokaryotes, are one component of a very useful technique to manipulate gene sequences or editing and gene expression with significant implications for respiratory research in the field of molecular biology. CRISPR technology is a promising tool that is easily adaptable for specific editing of DNA sequences of interest with a goal towards modifying or eliminating gene function. Among its many potential applications, CRISPR can be applied to correcting genetic defects as well as for therapeutic approaches for treatment. This review elucidates recent advances in CRISPR-Cas technology in airway diseases.

Common radiation dermatitis over radiation fields can be mild as minor erythema but can also be associated with blisters and skin desquamation. This phenomenon has been widely investigated and documented, especially in breast cancer patients. Obesity, smoking, and diabetes are known risk factors; however, we cannot predict the severity of radiation dermatitis prior to treatment. The overwhelming radiation recall dermatitis is an acute inflammatory reaction confined to previously irradiated areas that can be triggered when chemotherapy agents are administered after radiotherapy. This rare, painful skin reaction leads to treatment cessation or alteration. In this study, we investigate the feasibility of using thermography as a tool to predict the response of normal breast tissue and skin to radiation therapy and the risk of developing radiation recall dermatitis. Six women with viable in-breast tumor (breast cancer) and eight women who underwent tumor resection (lumpectomy) were monitored by a thermal camera prior to radiotherapy treatment (breast region) and on weekly basis, in the same environmental conditions, through the radiation course of treatment. One patient developed radiation recall dermatitis when treated with chemotherapy following radiation therapy, and needed intensive local treatments and narcotics with full recovery thereafter. Clinical and treatment data as well as response to radiation were collected prospectively. The ongoing thermal changes observed during the radiation treatment for all patients, with and without viable tumor in the breast, were documented, analyzed, and reported here with detailed comparison to the recognized data for the patient diagnosed with radiation recall dermatitis.

The human immunodeficiency virus (HIV) envelope glycoprotein protein 120 (gp120) induces neurotoxicity associated with HIV-associated neurocognitive disorders (HAND). Mechanism of Gp120-mediated neurotoxicity is primarily apoptosis. Currently, there are no therapeutics that address gp120 neurotoxicity. A biocompatible, efficacious therapeutic that easily crosses the blood-brain barrier (BBB) is needed to treat neuronal toxicity observed in HIV-infected individuals. Magnetic nanoparticles (MNPs) have successfully delivered anti-HIV agents across in vitro BBB transwell model. However, MNPs at high doses may damage cells. Exosomal extracellular vesicles (xEVs) are endogenous nanocarriers capable of crossing the BBB. Unlike MNPs, xEVs interact with cells in a paracrine or juxtracrine manner, lacking long-range site specificity. Here we investigated the efficacy of an MNP and xEV-coupled therapeutic (M-NEXT) as a nanocarrier for targeted delivery of anti-HIV fusion agent across the BBB to inhibit HIV-gp120 associated neuropathology. M-NEXT consisting of MNPs encapsulated within xEV carrying T20 peptide on the surface was synthesized and characterized via zeta potential, dynamic light scattering, and TEM imaging. Preliminary efficacy studies using SH-SY5Y cocultured with the in vitro BBB model showed that the M-NEXT-T20-fusion peptide protected neurons from HIV gp120-mediated neurotoxicity. Additionally, BBB integrity and permeability assessed via trans-endothelial resistance (TEER) and a Dextran-FITC transport assay was unaffected. SH-SY5Y viability measured by XTT assay was not significantly modulated by M-NEXT. In summary, preliminary findings support M-NEXT as effective nanocarriers for delivery of anti-HIV gp120 associated neurotoxicity agents.

Cancer treatment strategies require mathematical modeling of different coupled phenomena as well as uncertainty quantification of resulting computational solutions. Due to variability in thermophysical tissue properties among individuals, and even for the same individual under different physiological conditions, uncertainties in such parameters must appropriately be taken into account for accurate planning and control of hyperthermia and thermal ablation. The objective of this work is to estimate thermophysical properties of ex vivo tissue, with bovine muscle used for experiments. The Markov chain Monte Carlo method and approximate Bayesian computation algorithm are used to find solutions of the inverse problems examined in this work. These techniques provide a framework for not only solving the inverse problem but also finding uncertainty quantification.

Concussions are a major health concern due to the unpredictable onset and resolution of debilitating post-concussion symptoms. This review discusses physiological, structural and functional brain changes post-concussion, novel non-invasive medical imaging techniques to improve diagnosis, and the role exercise could play in concussion recovery. After sustaining a concussion, about 50% of youth and 20% of adults have symptoms that last for more than a month. Understanding concussion severity has become consequential in recent years as professional sports leagues have acknowledged their harmful short- and long-term effects. Despite these effects, concussed children and adults continue to return to activity and sport prior to a full recovery. This premature return can be enabled because routine clinical medical imaging techniques are unable to detect post-concussion brain damage. However, there have been advances in MRI approaches that clearly indicate brain damage due to concussion. In terms of recovery, rest has been the long-standing prescribed concussion treatment; however, subsymptom exacerbating exercise has been shown to be a safe and effective treatment option. Novel controlled aerobic exercise interventions have improved concussion outcomes by reducing recovery time and symptom severity.

Applications of fractional calculus in magnetic resonance imaging (MRI) have increased over the last twenty years. From the mathematical, computational, and biophysical perspectives, fractional calculus provides new tools for describing the complexity of biological tissues (cells, organelles, membranes and macromolecules). Specifically, fractional order models capture molecular dynamics (transport, rotation, and vibration) by incorporating power law convolution kernels into the time and space derivatives appearing in the equations that govern nuclear magnetic resonance (NMR) phenomena. Hence, it is natural to expect fractional calculus models of relaxation and diffusion to be applied to problems in NMR and MRI. Early studies considered the fractal dimensions of multi-scale materials in the non-linear growth of the mean squared displacement, assumed power-law decays of the spectral density, and suggested stretched exponential signal relaxation to describe non-Gaussian behavior. Subsequently, fractional order generalization of the Bloch, and Bloch-Torrey equations were developed to characterize NMR (and MRI) relaxation and diffusion. However, even for simple geometries, analytical solutions of fractional order equations in time and space are difficult to obtain, and predictions of the corresponding changes in image contrast are not always possible. Currently, a multifaceted approach using coarse graining, simulation, and accelerated computation is being developed to identify 'imaging' biomarkers of disease. This review surveys the principal fractional order models used to describe NMR and MRI phenomena, identifies connections and limitations, and finally points to future applications of the approach.

Mitochondria are among the most dynamic organelles regulating a wide array of cellular processes. They are the cellular hub for oxidative phosphorylation, energy production, and cellular metabolism, and they are important determinants of cell fate, as they control cell death/survival pathways. The mitochondrial network plays a critical role in cellular inflammatory responses, and mitochondria are central in many pathologic conditions such as chronic inflammatory and aging-associated degenerative diseases. Recent advancements in our understanding of the pathogenic pathways and the role of mitochondria therein have identified highly specific therapeutic targets in order to develop personalized nanomedicine approaches for treatment. A wide array of nanoparticle-based formulations has been employed for potential usage in both diagnosing and treating chronic and fatal conditions, with gold nanoparticles and liposomal encapsulation being of particular interest. In this review, we highlight and summarize the advantages and challenges of developing these nanoformulations for targeted and spatiotemporally controlled drug delivery. We discuss the potential of nanotherapy in neoplasms to target the mitochondrial regulated cell death pathways and recent seminal developments in liposomal nanotherapy against chronic inflammatory lung diseases. The need for further development of nanoparticle-based treatment options for neuroinflammatory and neurodegenerative conditions, such as Alzheimer's disease (AD), is also discussed.

Cardiovascular disease is a worldwide main cause of morbidity and mortality. Treatment alternatives include the use of cardiovascular implants that have generated a constant search for materials, and transformation processes that provide structures similar to those that need to be replaced. Among the biomaterials available for vascular implants, silk fibroin (SF) is of great interest because it is a natural, biodegradable, biocompatible protein. In addition, SF has outstanding mechanical properties and can be easily processed by various techniques. This article presents a general review of SF, its potential use as a biomaterial for vascular applications, and modifications that improve its hemocompatibility.