BMC biomedical engineering最新文献

Many people suffer from movement disability due to amputation or neurological diseases. Fortunately, with modern neurotechnology now it is possible to intercept motor control signals at various points along the neural transduction pathway and use that to drive external devices for communication or control. Here we will review the latest developments in human motor decoding. We reviewed the various strategies to decode motor intention from human and their respective advantages and challenges. Neural control signals can be intercepted at various points in the neural signal transduction pathway, including the brain (electroencephalography, electrocorticography, intracortical recordings), the nerves (peripheral nerve recordings) and the muscles (electromyography). We systematically discussed the sites of signal acquisition, available neural features, signal processing techniques and decoding algorithms in each of these potential interception points. Examples of applications and the current state-of-the-art performance were also reviewed. Although great strides have been made in human motor decoding, we are still far away from achieving naturalistic and dexterous control like our native limbs. Concerted efforts from material scientists, electrical engineers, and healthcare professionals are needed to further advance the field and make the technology widely available in clinical use.

Background: In virtual reality (VR) applications such as games, virtual training, and interactive neurorehabilitation, one can employ either the first-person user perspective or the third-person perspective to perceive the virtual environment; however, applications rarely offer both perspectives for the same task. We used a targeted-reaching task in a large-scale virtual reality environment (N=30 healthy volunteers) to evaluate the effects of user perspective on the head and upper extremity movements, and on user performance. We further evaluated how different cognitive challenges would modulate these effects. Finally, we obtained the user-reported engagement level under the different perspectives.

Results: We found that first-person perspective resulted in larger head movements (3.52±1.3m) than the third-person perspective (2.41±0.7m). First-person perspective also resulted in more upper-extremity movement (30.08±7.28m compared to 26.66±4.86m) and longer completion times (61.3±16.4s compared to 53±10.4s) for more challenging tasks such as the "flipped mode", in which moving one arm causes the opposite virtual arm to move. We observed no significant effect of user perspective alone on the success rate. Subjects reported experiencing roughly the same level of engagement in both first-person and third-person perspectives (F(1.58)=0.9,P=.445).

Conclusion: User perspective and its interaction with higher-cognitive load tasks influences the extent of movement and user performance in a virtual theater environment, and may influence the choice of the interface type (first or third person) in immersive training depending on the user conditions and exercise requirements.

Background: Stroke rehabilitation often uses the motor relearning concept that require patients to perform active practice of skill-specific training and to receive feedback. Treadmill training augmented with real-time visualisation feedback and functional electrical stimulation may have a beneficial synergistic effect on motor recovery. This study aims to determine the feasibility of this kind of enhanced treadmill training for gait rehabilitation among patients after stroke. A system for dynamic visualisation of lower-limb movement based on 3-dimentional motion capture and a computer timed functional electrical stimulation system was developed. Participants received up to 20-min enhanced treadmill training instead of their over-ground gait training once or twice a week for 6 weeks at Coathill hospital, Lanarkshire, United Kingdom. Number of training sessions attended, and training duration were used to assess feasibility. Ankle kinematics in the sagittal plane of walking with and without functional electrical stimulation support of the pre-tibial muscles were also compared and used to confirm the functional electrical stimulation was triggered at the targeted time.

Results: Six patients after stroke participated in the study. The majority of participants were male (5/6) with a age range from 30 to 84 years and 4/6 had left hemiplegia. All participants suffered from brain infarction and were at least 3 months after stroke. Number of training sessions attended ranged from 5 to 12. The duration of training sessions ranged from 11 to 20 min. No serious adverse events were reported. The computerised functional electrical stimulation to the pre-tibial muscles was able to reduce plantarflexion angle during the swing phase with statistical significance (p = 0.015 at 80%; p = 0.008 at 90 and 100% of the gait cycle).

Conclusions: It is safe and feasible to use treadmill gait training augmented with real-time visual feedback and computer-controlled functional electrical stimulation with patients after stroke in routine clinical practice.

Trial registration: NCT03348215. Registered 20 November 2017.

Background: A growing need exists for neuroscience platforms that can perform simultaneous chronic recording and stimulation of neural tissue in animal models in a telemetry-controlled fashion with signal processing for analysis of the chronic recording data and external triggering capability. We describe the system design, testing, evaluation, and implementation of a wireless simultaneous stimulation-and-recording device (SRD) for modulating cortical circuits in physiologically identified sites in primary somatosensory (SI) cortex in awake-behaving and freely-moving rats. The SRD was developed using low-cost electronic components and open-source software. The function of the SRD was assessed by bench and in-vivo testing.

Results: The SRD recorded spontaneous spiking and bursting neuronal activity, evoked responses to programmed intracortical microstimulation (ICMS) delivered internally by the SRD, and evoked responses to external peripheral forelimb stimulation.

Conclusions: The SRD is capable of wireless stimulation and recording on a predetermined schedule or can be wirelessly synchronized with external input as would be required in behavioral testing prior to, during, and following ICMS.

Background: Organoids derived from induced pluripotent stem (iPS) or embryonic stem (ES) cells have been evaluated as in vitro models of development and disease. However, maintaining these cells under long-term static culture conditions is difficult because of nutrition shortages and waste accumulation. To overcome these issues, perfusion culture systems are required for organoid technology. A system with a stable microenvironment, nutrient availability, and waste removal will accelerate organoid generation. The aim of this study was to develop a novel perfusion system for renal organoids by maintaining the air-liquid interface with a device fabricated using a 3D printer.

Results: Our results revealed slow flow at the organoid cultivation area based on microbead movement on the membrane, which depended on the perfusion rate under the membrane. Moreover, the perfused culture medium below the organoids via a porous membrane diffused throughout the organoids, maintaining the air-liquid interface. The diffusion rates within organoids were increased according to the flow rate of the culture medium under the membrane. The perfused culture medium also stimulated cytoskeletal and basement membrane re-organization associated with promotion tubular formation under 2.5 μL/min flow culture. In contrast, tubules in organoids were diminished at a flow rate of 10 μL/min.

Conclusions: Our liquid-air interface perfusion system accelerated organization of the renal organoids. These results suggest that suitable perfusion conditions can accelerate organization of epithelial cells and tissues in renal organoids in vitro.

Background: Therapy resistant ulcers are wounds that remain open for a long time period and often arise from chronic venous disease, prolonged pressure or diabetes. For healing of chronic wounds, revitalization of the inert wound bed, which is achieved by angiogenic sprouting of new blood vessels is of great importance. An alternative treatment option to conventional therapies is the use of skin substitutes: dermal (DS), epidermal (ES) or bi-layered skin substitutes (SS). The aim of this study was to determine the mode of action of an autologous SS, ES and DS with regards to endothelial cell proliferation, migration and angiogenic sprouting into a fibrin hydrogel.

Results: SS consists of a fully differentiated epidermis expanding over the acellular donor dermis (AD) which has become repopulated with fibroblasts. DS is the same construct as SS but without the epidermis and ES is the same construct as SS but without the fibroblasts. As a control, AD was used throughout. It was found that the bi-layered SS was the most potent substitute in inducing migration and sprouting of endothelial cells. The cross talk between dermis and epidermis resulted in the strongest induction of sprouting via VEGF and uPAR. ES stimulated sprouting more than DS again via VEGF and uPAR. The slight induction of sprouting mediated by DS was not mediated by VEGF, but was in part stimulated through uPAR.

Conclusion: This in vitro study supports our clinical observations that a bi-layered SS is a strong stimulator of angiogenesis and therefore has the potential to revitalize an inert wound bed.

Adenovirus (Ad) has been most extensively evaluated gene transfer vector in clinical trials due to facile production in high viral titer, highly efficient transduction, and proven safety record. Similarly, an oncolytic Ad, which replicates selectively in cancer cells through genetic modifications, is actively being evaluated in various phases of clinical trials as a promising next generation therapeutic against cancer. Most of these trials with oncolytic Ads to date have employed intratumoral injection as the standard administration route. Although these locally administered oncolytic Ads have shown promising outcomes, the therapeutic efficacy is not yet optimal due to poor intratumoral virion retention, nonspecific shedding of virion to normal organs, variable infection efficacy due to heterogeneity of tumor cells, adverse antiviral immune response, and short biological activity of oncolytic viruses in situ. These inherent problems associated with locally administered Ad also holds true for other oncolytic viral vectors. Thus, this review will aim to discuss various nanomaterial-based delivery strategies to improve the intratumoral administration efficacy of oncolytic Ad as well as other types of oncolytic viruses.

Background: Excessive extracellular matrix (ECM) deposition is a hallmark feature in fibrosis and tissue remodelling diseases. Typically, mesenchymal cells will produce collagens under standard 2D cell culture conditions, however these do not assemble into fibrils. Existing assays for measuring ECM production are often low throughput and not disease relevant. Here we describe a robust, high content, pseudo-3D phenotypic assay to quantify mature fibrillar collagen deposition which is both physiologically relevant and amenable to high throughput compound screening. Using pulmonary fibroblasts derived from patients with idiopathic pulmonary fibrosis (IPF), we developed the 'scar-in-a-jar' assay into a medium-throughput phenotypic assay to robustly quantify collagen type I deposition and other extracellular matrix (ECM) proteins over 72 h.

Results: This assay utilises macromolecular crowding to induce an excluded volume effect and enhance enzyme activity, which in combination with TGF-β₁ stimulation significantly accelerates ECM production. Collagen type I is upregulated approximately 5-fold with a negligible effect on cell number. We demonstrate the robustness of the assay achieving a Z prime of approximately 0.5, and % coefficient of variance (CV) of < 5 for the assay controls SB-525334 (ALK5 inhibitor) and CZ415 (mTOR inhibitor). This assay has been used to confirm the potency of a number of potential anti-fibrotic agents. Active compounds from the 'scar-in-a-jar' assay can be further validated for other markers of ECM deposition and fibroblast activation such as collagen type IV and α-smooth muscle actin exhibiting a 4-fold and 3-fold assay window respectively.

Conclusion: In conclusion, we have developed 'scar -in-a-jar is' into a robust disease-relevant medium-throughput in vitro assay to accurately quantify ECM deposition. This assay may enable iterative compound profiling for IPF and other fibroproliferative and tissue remodelling diseases.

Background: Mesenchymal stromal cells (MSCs) are widely used in clinical trials for bone repair and regeneration. Despite previous evidence showing a prominent osteogenic potential of 2D cultured CD271 enriched MSCs, the osteogenic potential of CD271 enriched cells cultured on 3D scaffold is unknown. Apatite-wollastonite glass ceramic (A-W) is an osteoconductive biomaterial shown to be compatible with MSCs. This is the first study comparing the attachment, growth kinetics, and osteogenic potential of two MSC populations, namely heterogeneous plastic adherence MSCs (PA-MSCs) and CD271-enriched MSCs (CD271-MSCs), when cultured on A-W 3D scaffold.

Results: The paired MSC populations were assessed for their attachment, growth kinetics and ALP activity using confocal and scanning electron microscopy and the quantifications of DNA contents and p-nitrophenyl (pNP) production respectively. While the PA-MSCs and CD271-MSCs had similar expansion and tri-lineage differentiation capacity during standard 2D culture, they showed different proliferation kinetics when seeded on the A-W scaffolds. PA-MSCs displayed a well-spread attachment with more elongated morphology compared to CD271- MSCs, signifying a different level of interaction between the cell populations and the scaffold surface. Following scaffold seeding PA-MSCs fully integrated into the scaffold surface and showed a stronger propensity for osteogenic differentiation as indicated by higher ALP activity than CD271-MSCs. Furthermore, A-W scaffold seeded uncultured non-enriched bone marrow mononuclear cells also demonstrated a higher proliferation rate and greater ALP activity compared to their CD271-enriched counterpart.

Conclusions: Our findings suggest that CD271-positive enrichment of a population is not beneficial for osteogenesis when the cells are seeded on A-W scaffold. Furthermore, unselected heterogeneous MSCs or BMMNCs are more promising for A-W scaffold based bone regeneration. This leads to a conclusion of broader clinical relevance for tissue engineering: on the basis of our observations here the osteogenic potential observed in 2D cell culture should not be considered indicative of likely performance in a 3D scaffold based system, even when one of the cell populations is effectively a subset of the other.

Background: Due to the presence of high noise level in tomographic series of energy filtered transmission electron microscopy (EFTEM) images, alignment and 3D reconstruction steps become so difficult. To improve the alignment process which will in turn allow a more accurate and better three dimensional tomography reconstructions, a preprocessing step should be applied to the EFTEM data series.

Results: Experiments with real EFTEM data series at low SNR, show the feasibility and the accuracy of the proposed denoising approach being competitive with the best existing methods for Poisson image denoising. The effectiveness of the proposed denoising approach is thanks to the use of a nonparametric Bayesian estimation in the Contourlet Transform with Sharp Frequency Localization Domain (CTSD) and variance stabilizing transformation (VST). Furthermore, the optimal inverse Anscome transformation to obtain the final estimate of the denoised images, has allowed an accurate tomography reconstruction.

Conclusion: The proposed approach provides qualitative information on the 3D distribution of individual chemical elements on the considered sample.