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Objective Patients with life- or limb-threatening severe injuries pose a challenge to prehospital services. Time-critical decision making and treatment are challenging because of occasional incomplete information, limited resources, adverse environments, and a range of basic and advanced technical skills available. To prepare for these infrequent critical situations, medical personnel from the helicopter emergency medical service at Oslo University Hospital developed a 1-day advanced trauma training course focusing on individual skills and teamwork during resuscitative procedures. Methods Participants were trained under supervision in teams on an established live tissue model with anesthetized pigs. A questionnaire-based evaluation was conducted before and after training to measure the feasibility of covering the allocated learning objectives in the time allotted and participants’ perception of any change in their skills as a result of the course. Results The self-reported skill level in all learning objectives improved significantly. Combining all learning objectives, the median self-reported skill level was significantly increased from 4 to 6 points (P Conclusion Experienced prehospital physicians and other health staff reported an increased level of skill and competence in lifesaving and limb-saving procedures after completing a brief, intense 1-day course using living anesthetized pigs and cadaver models.

All human tissues experience aging that eventually causes organ dysfunction and disease. Cellular senescence was discovered in fibroblasts cultured in vitro. In adults, it is a primary defense mechanism against cancer, but also a major contributor to lifespan limits and disorders associated with aging. To assess how human blood vessels change in an aged environment, we developed an elementary tissue model-on-a-chip that comprises an in vitro three-dimensional model of a blood vessel embedded in a collagen gel with young or senescent skin fibroblasts. We found that senescent fibroblasts mechanically altered the surrounding extracellular matrix by exerting excessive traction stress. We then found that senescent fibroblasts induced sprouting angiogenesis of a microvessel via their senescence-associated secretory phenotype (SASP). Finally, we gathered evidence that the mechanical changes of the microenvironment play a role in sustaining SASP-induced angiogenesis. The model proved useful in monitoring morphological changes in blood vessels induced by senescent fibroblasts while controlling the proportion of senescent cells, and enabled the study of SASP inhibitors, a class of drugs useful in aging and cancer research.

Osteochondral defects contain damage to both the articular cartilage and underlying subchon- dral bone, which remains a significant challenge in orthopedic surgery. Layered structure of bone, cartilage and the bone-cartilage interface must be taken into account in the case of biofabrication of the osteochondral (OC) interface. In this study, a dual layered OC interface was bioprinted using a newly developed aspiration-assisted bioprinting (AAB) technique, which has been the first time that scaffold-free bioprinting was applied to OC interface engineering. Tissue spheroids, made of human adipose-derived stem cells (ADSCs), were differentiated in three dimensions (3D) into chondrogenic and osteogenic spheroids, which were confirmed by immunostaining and histology qualitatively, and biochemistry assays and gene expression, quantitatively. Remarkably, the OC interface was bioprinted by accurate positioning of a layer of osteogenic spheroids onto a sacrificial alginate support followed by another layer of chondrogenic spheroids overlaid by the same support. Spheroids in individual zones fused and the maintenance of phenotypes in both zones confirmed the successful biofabrication of the histomorphologically-relevant OC interface. The biofabrication of OC tissue model without the use of polymeric scaffolds unveils great potential not only in regenerative medicine but also in drug testing and disease modeling for osteoarthritis.

Cutaneous squamous cell carcinoma (cSCC) causes approximately 10,000 deaths annually in the U. S. Current therapies are largely ineffective against metastatic and locally advanced cSCC. There is a need to identify novel, effective, and less toxic small molecule cSCC therapeutics. We developed a 3-dimensional bioprinted skin (3DBPS) model of cSCC tumors together with a microscopy assay to test chemotherapeutic effects in tissue. The full thickness SCC tissue model was validated using hematoxylin and eosin (H&E) and immunohistochemical histological staining, confocal microscopy, and cDNA microarray analysis. A nondestructive, 3D fluorescence confocal imaging assay with tdTomato-labeled A431 SCC and ZsGreen-labeled keratinocytes was developed to test efficacy and general toxicity of chemotherapeutics. Fluorescence-derived imaging biomarkers indicated that 50% of cancer cells were killed in the tissue after 1μM 5-Fluorouracil 48-hour treatment, compared to a baseline of 12% for untreated controls. The imaging biomarkers also showed that normal keratinocytes were less affected by treatment (11% killed) than the untreated tissue, which had no significant killing effect. Data showed that 5-Fluorouracil selectively killed cSCC cells more than keratinocytes. Our 3DBPS assay platform provides cellular-level measurement of cell viability and can be adapted to achieve nondestructive high-throughput screening (HTS) in bio-fabricated tissues.

Computer modeling and simulation is fast-moving towards clinical applications to advance cardiac diagnosis and aid treatment planning. As cardiac models become more popular and useful, the need to tailor these models for individual subjects has grown. Therefore, model identification becomes an important step of cardiac modeling. Cardiac model identification is a challenging task, particularly for simulation in high organizational scales such as tissue and organ scales, as the models are nonlinear and involve hidden ion channel gating variables. In this study, we proposed a two-stage model calibration algorithm to estimate the parameters of cardiac tissue model using membrane potential data. Specifically, an ensemble Kalman Filter (EnKF) is used in the first stage to track the membrane potentials and the hidden ion channel gating variables; the outputs from the EnKF are used as the initial values to calculate forward prediction in the second stage. The optimization algorithm minimizes the sum of squared errors in both stages through a coarse and a fine optimization. The proposed method is validated through multiple simulation designs, which shows good accuracy and efficiency.

The Tissue Mimicking Materials (TMM), are widely used in medical research, training, clinical simulators etc., to simulate the properties which are much more similar to that of the real biological tissues. In medical research TMM plays a vital role as the idealized tissue models to design and to test the methods, systems and clinical tools etc. In general TMM are made from bio polymers (agar, agarose, gelatin and gellan gum) and chemically synthesized polymers (polyvinyl alcohol, polymerized siloxanes, poly vinyl chlorides). The bio polymers have the properties of high mass fraction of water (>80%), due to this these biopolymers are not stable for long term use and also have a bacterial growth in a material. On the other hand, the chemically synthesized polymers have a lack of less similar properties to that of the skin. Ratio of softener and polymer, mass fraction of mineral oil and micronized glass beads are factors playing the major role in deciding the properties of TMM. Moreover, by using these TMM the mechanics of needle insertion such as applied force, friction between the needle and tissue and velocity of insertion etc. are studied to use it effectively in clinical applications. Even though, quite number of TMM are developed and tested, the TMM having properties which are very closer to real biological tissue at different aging periods are not available. Therefore, the researchers are working continuously to develop such kind of materials and it needs a depth understanding of available materials and its properties. This paper focuses on presenting a detailed literature study on development and characterization of various TMM, which will be useful for the researchers to develop new TMM for clinical training and clinical tool testing applications

Large-scale population testing is a key tool to mitigate the spread of respiratory pathogens, as in the current COVID-19 pandemic, where swabs are used to collect samples in the upper airways (e.g. nasopharyngeal and mid-turbinate nasal cavities) for diagnostics. However, the high volume of supplies required to achieve large-scale population testing has posed unprecedented challenges for swab manufacturing and distribution, resulting in a global shortage that has heavily impacted testing capacity world-wide and prompted the development of new swabs suitable for large-scale production. Newly designed swabs require rigorous pre-clinical and clinical validation studies that are costly and time consuming (i.e. months to years long); reducing the risks associated with swab validation is therefore paramount for their rapid deployment. To address these shortages, we developed a 3D-printed tissue model that mimics the nasopharyngeal and mid-turbinate nasal cavities, and we validated its use as a new tool to rapidly test swab performance. In addition to the nasal architecture, the tissue model mimics the soft nasal tissue with a silk-based sponge lining, and the physiological nasal fluid with asymptomatic and symptomatic viscosities of synthetic mucus. We performed several assays comparing standard flocked and injection-molded swabs. We quantified the swab pick-up and release, and determined the effect of viral load and mucus viscosity on swab efficacy by spiking the synthetic mucus with heat-inactivated SARS-CoV-2 virus. By molecular assays, we found that injected molded swabs performed similarly or superiorly in comparison to standard flocked swabs and we underscored a viscosity-dependent difference in cycle threshold values between the asymptomatic and symptomatic mucus for both swabs. To conclude, we developed an in vitro nasal tissue model, that corroborated previous swab performance data from clinical studies, with the potential of providing researchers with a clinically relevant, reproducible, safe, and cost-effective validation tool for the rapid development of newly designed swabs.

The three-dimensional bioprinting technologies have attracted increasing attention due to their flexibility in producing architecturally relevant tissue constructs. Here, we present an enabling vertical embedded extrusion bioprinting strategy using uniaxial or coaxial nozzles, which allows formation of vertical structures of homogeneous or heterogeneous properties in nature. By adjusting the bioprinting parameters, the characteristics of the bioprinted vertical patterns could be precisely controlled. Using this strategy, we demonstrated two proof-of-concept applications in tissue biofabrication. Specifically, intestinal villi and hair follicles, two liner-shaped tissue types in the human body, were successfully generated with the vertical embedded bioprinting method, reconstructing some of their key structures as well as restoring partial functions in vitro. Caco-2 cells in the bioprinted intestinal villus constructs proliferated and aggregated properly, also showing functional biomarker expressions such as ZO-1 and villin. Moreover, preliminary hair follicle structures featuring keratinized human keratinocytes and spheroid-shaped human dermal papilla cells were formed after vertical bioprinting and culturing. In summary, this vertical embedded extrusion bioprinting technique harnessing a uniaxial or coaxial format will likely bring further improvements in the reconstruction of certain human tissues and organs, especially those with a linear structure in nature, potentially leading to wide utilities in tissue engineering, tissue model engineering, and drug discovery. This article is protected by copyright. All rights reserved.

In order to design electromagnetic applicators for diagnostic and therapeutic applications, an adequate dielectric tissue model is required. In addition, tissue temperature will heavily influence the dielectric properties and the dielectric model should, thus, be extended to incorporate this temperature dependence. Thus, this work has a dual purpose. Given the influence of temperature, dehydration, and probe-to-tissue contact pressure on dielectric measurements, this work will initially present the first setup to actively control and monitor the temperature of the sample, the dehydration rate of the investigated sample, and the applied probe-to-tissue contact pressure. Secondly, this work measured the dielectric properties of porcine muscle in the 0.5–40 GHz frequency range for temperatures from 20 °C to 45 °C. Following measurements, a single-pole Cole–Cole model is presented, in which the five Cole–Cole parameters (ϵ∞, σs, Δϵ, τ, and α) are given by a first order polynomial as function of tissue temperature. The dielectric model closely agrees with the limited dielectric models known in literature for muscle tissue at 37 °C, which makes it suited for the design of in vivo applicators. Furthermore, the dielectric data at 41–45 °C is of great importance for the design of hyperthermia applicators.

IntroductionFull quantification of positron emission tomography (PET) data requires an input function. This generally means arterial blood sampling, which is invasive, labor-intensive and burdensome. There is no current, standardized method to fully quantify PET radiotracers with irreversible kinetics in the absence of blood data. Here, we present Source-to-Target Automatic Rotating Estimation (STARE), a novel, data-driven approach to quantify the net influx rate (Ki) of irreversible PET radiotracers, that requires only individual-level PET data and no blood data. We validate STARE with [18F]FDG PET and assess its performance using simulations.MethodsSTARE builds upon a source-to-target tissue model, where the tracer time activity curves (TACs) in multiple “target” regions are expressed at once as a function of a “source” region, based on the two-tissue irreversible compartment model, and separates target region Ki from source Ki by fitting the source-to-target model across all target regions simultaneously. To ensure identifiability, data-driven, subject-specific anchoring is used in the STARE minimization, which takes advantage of the PET signal in a vasculature cluster in the FOV that is automatically extracted and partial volume-corrected. To avoid the need for any a priori determination of a single source region, each of the considered regions acts in turn as the source, and a final Ki is estimated in each region by averaging the estimates obtained in each source rotation.ResultsIn a large dataset of [18F]FDG human scans (N=69), STARE Ki estimates were in good agreement with corresponding arterial blood-based estimates (regression slope=0.88, r=0.80), and were precisely estimated, as assessed by comparing STARE Ki estimates across several runs of the algorithm (coefficient of variation across runs=6.74 ± 2.48%). In simulations, STARE Ki estimates were largely robust to factors that influence the individualized anchoring used within its algorithm.ConclusionThrough simulations and application to [18F]FDG PET data, feasibility is demonstrated for STARE blood-free, data-driven quantification of Ki. Future work will include applying STARE to PET data obtained with a portable PET camera and to other irreversible radiotracers.

Introduction We evaluate diagnostic radiology residents’ perceptions of an ultrasound-guided and stereotactic breast biopsy simulator used at an academic medical center. This simulator is low-cost and easily reproducible. We aim to understand if this simulator improves residents’ self-reported confidence in performing breast biopsy procedures on live patients. Methods Twenty-eight diagnostic radiology residents were instructed in how to perform ultrasound-guided breast biopsies and stereotactic breast biopsies using real biopsy and imaging equipment, but with tissue models in lieu of live persons. The hands-on experience was preceded by a didactic lecture. The ultrasound-guided tissue model was created with blueberries that were inserted in tofu, and the stereotactic tissue model was created by placing crushed calcium carbonate tablets into cored eggplant. Residents were asked to fill out a survey before and after participating in the simulation, where they self-reported their confidence level at performing ultrasound-guided and stereotactic breast biopsies. Results Twenty-eight diagnostic radiology residents participated in the simulation. All residents completed the pre-simulation survey and of these residents, twenty-one completed the post-simulation survey. Prior to the simulation residents reported a median confidence level of 3.5 out of 10 in performing ultrasound-guided breast biopsies, and a median confidence level of 1.0 out of 10 in performing stereotactic-guided breast biopsies. After the simulation, residents reported a median confidence level of 7.0 out of 10 in performing ultrasound-guided breast biopsies, and a median confidence level of 3.0 out of 10 in performing stereotactic-guided breast biopsies. Increases in resident confidence level were statistically significant for both biopsy types (p < 0.01). Conclusion Simulated biopsies can increase the confidence of diagnostic radiology residents that are learning to perform breast biopsies before they perform real biopsies on live patients. Providing simulation training and thereby improving resident confidence may help reduce physician error and patient harm due to poor biopsy techniques.

The viscoelastic behavior of hydrogel matrices sensitively influences the cell behavior in 3D culture and biofabricated tissue model systems. Previous reports have demonstrated that cells tend to adhere, spread, migrate and proliferate better in hydrogels with pronounced stress relaxation. However, it is currently unknown if cells respond more sensitively to the amplitude of stress relaxation, or to the relaxation time constant. To test this, we compare the behavior of fibroblasts cultured for up to 10 days in alginate and oxidized alginate hydrogels with similar Young’s moduli but diverging stress relaxation behavior. We find that fibroblasts elongate, migrate and proliferate better in hydrogels that display a higher stress relaxation amplitude. By contrast, the cells’ response to the relaxation time constant was less pronounced and less consistent. Together, these data suggest that it is foremost the stress relaxation amplitude of the matrix that determines the ability of cells to locally penetrate and remodel the matrix, which subsequently leads to better spreading, faster migration, and higher cell proliferation. We conclude that the stress relaxation amplitude is a central design parameter for optimizing cell behavior in 3-D hydrogels.

The present study was performed to screen in vitro potential acute inhalation toxicity using an EpiAirwayTM tissue model (human tracheal/bronchial tissue) for the nano-sized titanium dioxide, GST manufactured as a photocatalyst through of sludge recycling and to compare with P-25 a commercialized photocatalytic material. According to the protocol provided by in vitro tissue manufacturer, the GST was exposure to the tissue for 3 hours in 450, 500, 650, 850 mg/mL concentration after preliminary dose range finding study and then tissue viability (%, IC75) was calculated using the MTT assay. Besides, the histopathological observation was performed to compare to the MTT assay. As a result of study, IC75 could not be confirmed at 850 mg/mL in both GST and P-25 and the grade was confirmed to be IC75> 600 mg/mL in vitro model tissue category. Therefore, it was considered that the GHS category could be classified as ‘No classification’ in screening method for potential acute inhalation toxicity. Also, not the morphological effects of epithelial cells in tissue model were observed compared with the vehicle control and histological findings were similar to the results of MTT Viability assay. Based on these results, the potential acute inhalation toxicity for GST produced through sludge recycling using in vitro tissue model inhalation toxicity showed that it could be non-hazardous substance. However, further study (in vivo study, etc.) is thought to be needed to ascertain whether GST is a toxic effect or safe.

Rationale: Particulate matter with an aerodynamic diameter equal or less than 2.5 µm (PM2.5) represents a main constituent of polluted air with a potential detrimental impact on human health. Objec...

Size and function of bioartificial tissue models are still limited due to the lack of blood vessels and dynamic perfusion for nutrient supply. In this study, we evaluated the use of cytocompatible methacryl-modified gelatin for the fabrication of a hydrogel-based tube by dip-coating and subsequent photo-initiated cross-linking. The wall thickness of the tubes and the diameter were tuned by the degree of gelatin methacryl-modification and the number of dipping cycles. The dipping temperature of the gelatin solution was adjusted to achieve low viscous fluids of approximately 0.1 Pa s and was different for gelatin derivatives with different modification degrees. A versatile perfusion bioreactor for the supply of surrounding tissue models was developed, which can be adapted to several geometries and sizes of blood-vessel mimicking tubes. The manufactured bendable gelatin tubes were permeable for water and dissolved substances, like Nile Blue and serum albumin. As a proof of concept, human fibroblasts in a three-dimensional collagen tissue model were successfully supplied with nutrients via the central gelatin tube under dynamic conditions for 2 days. Moreover, the tubes could be used as scaffolds to build-up a functional and viable endothelial layer. Hence, the presented tools can contribute to solving current challenges in tissue engineering.

Ischemia reperfusion injury (IRI) involvement in pressure ulcers (PU) progression via a surge of oxidative stress and inflammatory responses is well documented. IRI strongly depends on the mechanical loading history. We present a generalized IRI model considering external loading, dynamic tissue healing capacity, accumulating mechanical and reperfusion-mediated damages and competing repair processes of saturating nature. Reperfusion depends on strain and strain rate to enhance loading history sensitivity. Tissue-specific ulceration susceptibility is assumed dependent on variable accumulated damage. We study damage evolution under cyclic loading having several strain expulsion profiles and demonstrate load relief history has critical impact on PU progression. Abrupt load removal generally follows existing models representing extreme repair/damage. We show (first time in silico) that under certain conditions (previously experimentally identified), IRI becomes repairing rather than damaging. In particular, we recapitulate the preconditioning and postconditioning IRI hallmarks. Finally, it is customary among physicians and nurses to promptly alleviate mechanical load applied to patients lying in bed for extended periods and in risk of developing PUs. We demonstrate this practice can be harmful. If load removal is performed early while reperfusion is still beneficial, then this conduct is suitable. However, if critical tissue damage has been crossed, then abrupt expulsion can constitute the worst-case scenario for patient outcome. If no preliminary patient documentation is available, we recommend gradual load removal since risks of accelerated damage eventually leading to ulceration supersede the improved repair potential benefit.

Aim: A revised method of preparing the mimetic tissue model for quantitative imaging mass spectrometry (IMS) is evaluated. Concepts of assessing detection capability are adapted from other imaging or mass spectrometry (MS)-based technologies to improve upon the reliability of IMS quantification. Materials & methods: The mimetic tissue model is prepared by serially freezing spiked-tissue homogenates into a cylindrical mold to create a plug of tissue with a stepped concentration gradient of matrix-matched standards. Weighted least squares (WLS) linear regression is applied due to the heteroscedastisity (change in variance with intensity) of most MS data. Results & conclusions: Imaging poses several caveats for quantification which are unique compared with other MS-based methods. Aspects of the design, construction, application, and evaluation of the matrix-matched standard curve for the mimetic tissue model are discussed. In addition, the criticality of the ion distribution in the design of a purposeful liquid chromatography coupled to mass spectrometry (LC–MS) validation is reviewed. [Formula: see text]

Achieving adequate surgical exposure is fundamental to good surgical practice. Traditionally, in the repair of ventral and open inguinal hernias, this has been accomplished with the aid of self-retaining retractors or by extending the incision length. We propose that using disposable wound protectors, surgical exposure will be improved for a given incision length in the repair of ventral and open inguinal hernias, compared to traditional methods. Through the use of an animal tissue model, we compared incisions of varying lengths and measured the dimensions of the exposure achieved with disposable wound protectors (Alexis™) and a Mollison self-retainer. We calculated the surface area and, therefore, exposure gained using the specified wound retraction devices and compared the results. The average superficial surface area of wound with a self-retainer compared to the small and extra-small disposable wound protector was 2.65 cm2 vs 2.27 cm2 (small) and 2.2 cm2 (extra-small) for 2 cm incision length, 3.6 cm2 vs 4.93 cm2 and 4.2 cm2 for 3 cm incision length, 5.19 cm2 vs 8.25 cm2 and 6.27 cm2 for 4 cm incision length, 6.17 cm2 vs 12.25 cm2 and 9.07 cm2 for 5 cm incision length, and 8.75 cm2 vs 16.73 cm2 and 10.78 cm2 for 6 cm incision length [p = 0.038 (small) and p = 0.049 (extra-small)]. Our results show a statistically significant increase in surface area of a wound for each incision length when a disposable wound protector was used for exposure, compared to a self-retainer. Our results demonstrate that the use of disposable wound protectors provides superior surgical exposure for a given incision length compared to traditional techniques in the repair of ventral and open inguinal hernia repairs.

Background: Significant advances in minimally invasive implantation of mechanical circulatory support devices have been made. These approaches are technically challenging and associated with a learning curve. Simulation and training opportunities in these techniques are limited. We developed a high-fidelity novel model for minimally invasive left ventricular assist device implantation.Material and methods: Using a modified inanimate simulator (LSI SOLUTIONS®) and an animal tissue model, a hybrid simulator was created, with a porcine ex vivo heart secured within the inanimate simulator in the normal anatomic position. Key components of the minimally invasive left ventricular assist device implantation were performed, including left ventricular apical coring, attachment of the apical ring, attachment of the assist device, and creation of the aortic-outflow graft anastomosis.Results: A novel composite inanimate and tissue model for minimally invasive left ventricular assist device implantation was successfully developed. These simulation techniques were reproducible, and the model demonstrated ability to successfully simulate key components of the procedure.Conclusions: This high-fidelity, reproducible hybrid model allows for crucial components of minimally invasive LVAD implantation to be performed. This model has the potential to be used as an adjunct to surgical training, providing a safe and controlled learning environment for trainees to acquire skills in minimally invasive LVAD implantation.

Cervical insufficiency is an important cause of preterm birth, which leads to severe newborn complications. Standard treatment for cervical insufficiency is cerclage, which has variable success rates, resulting in a clinical need for alternative treatments. Our objective was to develop an ex vivo model of softened cervical tissue to study an injectable silk-based hydrogel as a novel alternative treatment for cervical insufficiency. Cervical tissue from non-pregnant women was enzymatically treated and characterized to determine tissue hydration, collagen organization, and mechanical properties via unconfined compression. Enzymatic treatment led to an 86 ± 7.9% decrease in modulus which correlated to a decrease in collagen organization as observed by differences in collagen birefringence. The softened tissue was injected with a crosslinked silk-hyaluronic acid composite hydrogel. After injection, the mechanical properties and volume increase of the hydrogel-treated tissue were measured resulting in a 54 ± 16% volume increase with minimal effect on tissue mechanical properties. In addition, cervical fibroblasts on silk-hyaluronic acid hydrogels remained viable and exhibited increased proliferation and metabolic activity over 5 days. Overall, this study developed an ex vivo pregnant-like human tissue model to assess cervical augmentation and showed the potential of silk-based hydrogels as an alternative treatment for cervical insufficiency.

Idiopathic pulmonary fibrosis (IPF) is a complex disease of unknown etiology with no current curative treatment. Modeling pulmonary fibrotic (PF) tissue has the potential to improve our understanding of IPF disease progression and treatment. Rodent animal models do not replicate human fibroblastic foci (Hum-FF) pathology, and current iterations of in vitro model systems (e.g., collagen hydrogels, polyacrylamide hydrogels, and fibrosis-on-chip systems) are unable to replicate the three-dimensional (3D) complexity and biochemical composition of human PF tissue. Herein, we fabricated a 3D bioengineered pulmonary fibrotic (Eng-PF) tissue utilizing cell laden silk collagen type I dityrosine cross-linked hydrogels and Flexcell bioreactors. We show that silk collagen type I hydrogels have superior stability and mechanical tunability compared to other hydrogel systems. Using customized Flexcell bioreactors, we reproduced Hum-FF-like pathology with airway epithelial and microvascular endothelial cells. Eng-PF tiss...

Summary Purpose To provide a high-fidelity, animal tissue-based model for the advanced surgical simulation of laparoscopic dismembered pyeloplasty in infants and children. Materials and methods A previously described animal tissue model using chicken crop was surgically modified and attached to piglet kidney specimens in order to provide organ model realistically resembling infant and children hydronephrosis for simulation of dismembered laparoscopic pyeloplasty. Dismembered pyeloplasty could then be carried out in a standard pelvi-trainer using a standard instrumentation as in a regular case. Results The model created could prove to be a high-fidelity, animal tissue model for the surgical simulation of dismembered pyeloplasty. The surgical modification of the used animal tissues of chicken crop and piglet kidney respectively used in this fusion model was able to provide a high grade of resembling a realistic organ situs for infant and pediatric pyeloplasty, respectively. The surgical procedure could be carried out as a simulation of a regular case while providing high-grade realistic anatomy, adequate sizes of a dilated renal pelvis and of the ureter, respectively. Biological as well as haptic conditions of the tissue were able to resemble human tissue in a high grade as well. Discussion Despite a live animal model has been described for dismembered pyeloplasty, its time-consuming creation and possible conflict concerning animal welfare cadaver models are more practicable for daily simulation. In literature so far animal-tissue models described range from folded chicken skin to a chicken crop model. While these types of models have its own advantages and disadvantages none of them provide adequate anatomical relations. By dissecting chicken crop and fixating it to a piglet's kidney this limitation could be overcome and furthermore will enable future modifications for a perfused model for laparoscopic dismembered pyeloplasty. Conclusion The fusion of a previously described tissue model of chicken crop for simulation of pyeloplasty along with also previously used piglet kidneys for surgical simulation can provide a highly realistic model for surgical simulation of pediatric dismembered laparoscopic pyeloplasty. In addition, this model rules out the disadvantage of native animal kidney specimens which the lack of pathology of a dilated renal pelvis. Surgical modification is an established method to provide high-fidelity animal tissue models for surgical simulation and therefore training of complex procedures, respectively. For simulation purposes in pediatric laparoscopic urology, i.e., reconstructive procedures such as dismembered pyeloplasty this model appears to be promising in terms of providing realistic pathology in pediatric dimensions.

Irreversible Electroporation (IRE) is a promising clinical ablation therapy for the treatment of cancer, but issues with the generation of heat must be solved before safe and effective clinical results can be obtained. In the present study, we show that a metal stent will not be noticeably heated up by IRE pulses under typical clinical conditions. Derivation of this non-intuitive result required the application of Maxwell's equations to the tissue-stent configuration. Subsequently, straightforward and arguably accurate simplifications of the electric field generated by two needles in tissue surrounding a metal stent have enabled the modeling of the heat generation and the transport of heat in IRE procedures. Close to a stent that is positioned in between two needles, temperatures in a typical run of 100 s, 1 Hz pulses, may remain notably lower than without the stent. This is the explanation of the experimentally observed low temperature rim of viable tissue around the stent, whereas all tissue was non-viable without stent, found in tissue model experiments.

Dynamic, in vivo measurement of the optical properties of biological tissues is still an elusive and critically important problem. Here we develop a technique for inverting a Monte Carlo simulation to extract tissue optical properties from the statistical moments of the spatio-temporal response of the tissue by training a 5-layer fully connected neural network. We demonstrate the accuracy of the method across a very wide parameter space on a single homogeneous layer tissue model and demonstrate that the method is insensitive to parameter selection of the neural network model itself. Finally, we propose an experimental setup capable of measuring the required information in real time in an in vivo environment and demonstrate proof-of-concept level experimental results.

Background Sudden cardiac death (SCD) is a leading cause of death worldwide, and the majority of SCDs are caused by acute ventricular arrhythmias (VAs). Early afterdepolarizations (EADs) are an important trigger of VA under pathological conditions, e.g., inherited or acquired long QT syndrome (LQTS). However, it remains unclear how EAD events at the cellular level are spatially organized at the tissue level to induce and maintain ventricular arrhythmias and whether the spatial-temporal patterns of EADs at the tissue level are associated with abnormal T-wave morphologies that are often observed in LQTS, such as broad-based, notched or bifid; late appearance; and pointed T-waves. Result Here, a tissue model of the Purkinje-ventricular system (PVS) was developed to quantitatively investigate the complex spatial-temporal dynamics of EADs during T-wave abnormalities, and we found that (1) while major inhibition of ICaL can substantially reduce the excitability of the PVS leading to conduction failures, moderate ICaL inhibition can promote occurrences of AP alternans at short cycle lengths (CLs), and EAD events preferentially occur with a major reduction of IKr (> 50%) at long CLs; (2) with a minor reduction of ICaL, spatially synchronized steady-state EAD events with inverted and biphasic T-waves can be “weakened” into beat-to-beat concurrences of spatially synchronized EADs and T-wave alternans, and as pacing CLs increase, beat-to-beat concurrences of localized EADs with late-appearing and pointed T-wave morphologies can be observed; (3) under certain conditions, localized EAD events in the midmyocardium may trigger slow uni-directional electric propagation with inverted (antegrade) or upright (retrograde) broad-based T-waves; (4) spatially discordant EADs were typically characterized by desynchronized spontaneous onsets of EAD events between two groups of PVS tissues with biphasic T-wave morphologies, and they can evolve into spatially discordant oscillating EAD patterns with sustained or self-terminated alternating EAD and electrocardiogram (ECG) patterns. Conclusion Our results provide new insights into the spatiotemporal aspects of the onset and development of EADs and suggest possible mechanistic links between the complex spatial dynamics of EADs and T-wave morphologies.

In this work, we present the open source “Simulation and Image Processing for Photoacoustic Imaging (SIMPA)” toolkit that facilitates simulation of multispectral photoacoustic images by streamlining the use of state-of-the-art frameworks that numerically approximate the respective forward models. SIMPA provides modules for all the relevant steps for photoacoustic forward simulation: tissue modelling, optical forward modelling, acoustic modelling, noise modelling, as well as image reconstruction. We demonstrate the capabilities of SIMPA by performing image simulation using MCX and k-Wave for the optical and acoustic forward modelling, as well as an experimentally determined noise model and a custom tissue model.

The subject of the study in the article is to study the method of excitation of human body tissues using an electric current. The purpose of the work is to develop a method for exciting local current in a human body affecting the microcirculation of blood and excitability of local areas of muscle tissue during the treatment process. The article solves the following tasks: the creation of a model pattern of fabric, the rationale for the generation of electric current inside the sample, the development of the design of the current generation system and measuring the electrical response of the model sample of the tissue on the occurrence of electric current, determining the size and spatial current distribution in the model sample of the fabric, comparison The obtained current values with known and admissible in medical practice its values, determination of the advantages of the proposed method of excitation of current compared to the traditional used in medicine. The following methods were used: analysis of scientific publications for the subject of the study, the calculation of the expected current parameters in the model sample, the method of designing the nodes of the current generation and measurement system of the electrical response, the experimental method of excitation of the current and measuring the sample response to it. The following results were obtained: a new acoustic-magnetic method of exciting electric current in local areas of muscle tissue is justified, which allows determining for them the optimal values of the therapeutic current and the value of its threshold value. model samples of muscle tissue are created, a magnetohydrodynamic method of generating electric current inside the patient's body is justified, design of a system for generating current and measuring the electrical response of a model fabric sample to the occurrence of electric current in it; determining the magnitude and spatial distribution of the current in the model fabric sample; comparison of obtained current values with known and permissible values in medical practice and proved their safety for a person. Calculated ratios are obtained, which connect value of excited local current with parameters of ultrasonic radiation, external permanent magnetic field and biological medium. The materials have been found that the current density excited in the local area of the biological medium is independent of the ultrasound frequency and is determined mainly by the intensity of the ultrasound and the constant magnetic field. The advantages of the current excitation method according to the present invention over the conventional galvanic method of passing current through the patient's skin are the ability to generate current in any desired local area of the patient's tissue and its complete safety. Conclusions: The scientific foundations of the new method of excitation of local current inside the human body have been developed and experimentally tested on model samples. Using this method can significantly increase the effectiveness of the treatment process based on the effect of current on blood microcirculation in predetermined areas of muscle tissue and for the first time will allow distinguishing and determining with high accuracy thresholds of their excitability by electric current., Предметом исследования в статье является изучение способа возбуждения тканей организма человека с помощью электрического тока. Цель работы – разработка метода возбуждения локального тока в теле человека, влияющего на микроциркуляцию крови и возбудимость локальных участков мышечной ткани в течении лечебного процесса. В статье решаются следующие задачи: создание модельного образца ткани, обоснование метода генерации электрического тока внутри образца, разработка конструкции системы генерации тока и измерения электрического отклика модельного образца ткани на возникновение в ней электрического тока, определение величины и пространственного распределения тока в модельном образце ткани, сравнение полученных значений тока с известными и допустимыми в медицинской практике его значениями, определение преимуществ предлагаемого способа возбуждения тока по сравнению с традиционным, используемом в медицине. Используются такие методы: анализ научных публикаций по предмету исследования, расчет ожидаемых параметров тока в модельном образце, метод конструирования узлов системы генерации тока и измерения электрического отклика, экспериментальный метод возбуждения тока и измерения отклика образца на него. Получены следующие результаты: обоснован новый акусто-магнитный метод возбуждения электрического тока в локальных участках мышечной ткани, который позволяет определять для них оптимальные значения лечебного тока и величину его порогового значения, созданы модельные образцы мышечной ткани, обоснован магнитогидродинамический способ генерации электрического тока внутри тела пациента, создана конструкция системы генерации тока и измерения электрического отклика модельного образца ткани на возникновение в ней электрического тока, определена величина и пространственное распределения тока в модельном образце ткани, выполнено сравнение полученных значений тока с известными и допустимыми в медицинской практике его значениями и доказана их безопасность для человека. Получены расчетные соотношения, связывающие величину возбуждаемого локального тока с параметрами ультразвукового излучения, внешнего постоянного магнитного поля и биологической среды. Установлено, что плотность тока, возбуждаемого в локальном участке биологической среды, не зависит от частоты ультразвука и определяется в основном величинами интенсивности ультразвука и постоянного магнитного поля. Преимуществами предлагаемого метода возбуждения тока по сравнению с традиционным гальваническим методом пропускания тока через кожу пациента являются возможность создавать ток в любом требуемом локальном участке ткани пациента и полная его безопасность. Выводы: разработаны и экспериментально проверены на модельных образцах научные основы нового метода возбуждения локального тока внутри тела человека. Использование этого метода может существенно повысить эффективность лечебного процесса на основе воздействия тока на микроциркуляцию крови в заранее заданных участках мышечной ткани и впервые позволит различать и определять с высокой точностью пороги их возбудимости электрическим током., Предметом дослідження в статті є вивчення способу збудження тканин організму людини за допомогою електричного струму. Мета роботи – розробка методу збудження локального струму в тілі людини, що впливає на мікроциркуляцію крові і збудливість локальних ділянок м'язової тканини в перебігу лікувального процесу. У статті вирішуються наступні завдання: створення модельного зразка тканини, обгрунтування методу генерації електричного струму всередині зразка, розробка конструкції системи генерації струму і вимірювання електричного відгуку модельного зразка тканини на виникнення в ній електричного струму, визначення величини і просторового розподілу струму в модельному зразку тканини, порівняння отриманих значень струму з відомими і допустимими в медичній практиці його значеннями, визначення переваг запропонованого способу збудження струму в порівнянні з традиційним, який використовується в медицині. Використовуються такі методи: аналіз наукових публікацій з предмету дослідження, розрахунок очікуваних параметрів струму в модельному зразку, метод конструювання вузлів системи генерації струму і вимірювання електричного відгуку, експериментальний метод збудження струму і вимірювання відгуку зразка на нього. Отримані наступні результати: обґрунтовано новий акусто-магнітний метод збудження електричного струму в локальних ділянках м'язової тканини, який дозволяє визначати для них оптимальні значення лікувального струму і величину його порогового значення, створені модельні зразки м'язової тканини, обгрунтований магнітогідродинамічний спосіб генерації електричного струму всередині тіла пацієнта, створена конструкція системи генерації струму і вимірювання електричного відгуку модельного зразка тканини на виникнення в ній електричного струму, визначена величина і просторовий розподіл струму в модельному зразку тканини, виконано порівняння отриманих значень струму з відомими і допустимими в медичній практиці його значеннями і доведено їх безпечність для людини . Отримано розрахункові співвідношення, що зв'язують величину збудження локального струму з параметрами ультразвукового випромінювання, зовнішнього постійного магнітного поля і біологічного середовища. Встановлено, що щільність струму, що збуджується в локальній ділянці біологічного середовища, не залежить від частоти ультразвуку і визначається в основному величинами інтенсивності ультразвуку і постійного магнітного поля. Перевагами запропонованого методу збудження струму в порівнянні з традиційним гальванічним методом пропускання струму через шкіру пацієнта є можливість створювати струм в будь-якому необхідному локальній ділянці тканини пацієнта і повна його безпека. Висновки: pозроблено та експериментально перевірено на модельних зразках наукові основи нового методу збудження локального струму всередині тіла людини. Використання цього методу може істотно підвищити ефективність лікувального процесу на основі впливу струму на мікроциркуляцію крові в заздалегідь заданих ділянках м'язової тканини і вперше дозволить розрізняти і визначати з високою точністю пороги їх збудливості електричним струмом.

Successful detection and prevention of brain injuries relies on the quantitative identification of cellular injury thresholds associated with the underlying pathology. Here, by combining a recently developed inertial microcavitation rheology technique with a 3D in vitro neural tissue model, we quantify and resolve the structural pathology and critical injury strain thresholds of neural cells occurring at high loading rates such as encountered in blast, cavitation or directed energy exposures. We find that neuronal dendritic spines characterized by MAP2 displayed the lowest physical failure strain at 7.3%, whereas microtubules and filamentous actin were able to tolerate appreciably higher strains (14%) prior to injury. Interestingly, while these critical injury thresholds were similar to previous literature values reported for moderate and lower strain rates ( 100 1/s), the pathology of primary injury reported here was distinctly different by being purely physical in nature as compared to biochemical activation during apoptosis or necrosis. Statement of Significance Mitigation and prevention of cellular injury is challenging in part due to the lack of quantitative correlation between mechanical insult and cellular pathology, especially at high deformation rates (>104 s−1) that occur in blast and directed energy related brain injury, or laser and sonic-based medical procedures. By utilizing a recently developed inertial microcavitation rheology technique for generating high-rate deformations in a 3D in vitro neural tissue model, we quantitatively correlate critical stretch, strain and stress-based injury criteria to observed cell pathology. These quantitative experimental measurements provide unprecedented new detail into the cellular pathology of neural tissues affected by high-rate injury including the first quantitative high-rate injury threshold metrics.

Bordetella pertussis is a highly contagious pathogen which causes whooping cough in humans. A major pathophysiology of infection is the extrusion of ciliated cells and subsequent disruption of the respiratory mucosa. Tracheal cytotoxin (TCT) is the only virulence factor produced by B. pertussis that has been able to recapitulate this pathology in animal models. This pathophysiology is well characterized in a hamster tracheal model, but human data are lacking due to scarcity of donor material. We assessed the impact of TCT and lipopolysaccharide (LPS) on the functional integrity of the human airway mucosa by using in vitro airway mucosa models developed by co-culturing human tracheobronchial epithelial cells and human tracheobronchial fibroblasts on porcine small intestinal submucosa scaffold under airlift conditions. TCT and LPS either alone and in combination induced blebbing and necrosis of the ciliated epithelia. TCT and LPS induced loss of ciliated epithelial cells and hyper-mucus production which interfered with mucociliary clearance. In addition, the toxins had a disruptive effect on the tight junction organization, significantly reduced transepithelial electrical resistance and increased FITC-Dextran permeability after toxin incubation. In summary, the results indicate that TCT collaborates with LPS to induce the disruption of the human airway mucosa as reported for the hamster tracheal model.

Metabolic modeling enables the study of human metabolism in healthy and in diseased conditions, e.g., the prediction of new drug targets and biomarkers for metabolic diseases. To accurately describe blood and urine metabolite dynamics, the integration of multiple metabolically active tissues is necessary. We developed a dynamic multi-tissue model, which recapitulates key properties of human metabolism at the molecular and physiological level based on the integration of transcriptomics data. It enables the simulation of the dynamics of intra-cellular and extra-cellular metabolites at the genome scale. The predictive capacity of the model is shown through the accurate simulation of different healthy conditions (i.e., during fasting, while consuming meals or during exercise), and the prediction of biomarkers for a set of Inborn Errors of Metabolism with a precision of 83%. This novel approach is useful to prioritize new biomarkers for many metabolic diseases, as well as for the integration of various types of personal omics data, towards the personalized analysis of blood and urine metabolites.