Design and Fabrication of a Soft Robotic Direct Cardiac Compression Device

A direct cardiac compression (DCC) device is an active sleeve that is surgically placed around the heart to help the failing heart to pump without contacting blood. Soft robotic techniques enable fabrication of a conformable DCC device containing modular actuators oriented in a biomimetic manner that can restore the natural motion of the heart and provide tunable active assistance. In this paper we describe the fabrication of a DCC device; the optimization of pneumatic actuators, their integration into a matrix with a modulus in the range of cardiac tissue and methods to affix this device to the heart wall. Pneumatic air muscles (PAMs) were fabricated using a modified McKibben technique and four types of internal bladders; low durometer silicone tubes molded in-house, polyester terephthalate (PET) heat shrink tubing, nylon medical balloons and thermoplastic urethane (TPU) balloons thermally formed in-house. Balloons were bonded to air supply lines, placed inside a braided nylon mesh with a 6.35mm resting diameter and bonded at one end. When pressurized to 145kPa silicone tubes failed and PET, nylon and TPU actuators generated isometric axial forces of 14.28, 19.65 and 19.05N respectively, with axial contractions of 33.11, 28.69 and 37.54%. Circumferential actuators placed around the heart reduced the cross-sectional area by 33.34% and 50.63% for silicone and TPU actuators respectively. PAMs were integrated into a soft matrix in a biomimetic orientation using three techniques; casting, thermal forming and layering. Designs were compared on an in vitro cardiac simulator and generated a volumetric displacement of up to 96ml when actuated for 200ms at 1Hz. Layering produced the lowest profile device that successfully conformed to the heart and this design is currently undergoing in vivo testing.

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Dangshen Erling Decoction Ameliorates Myocardial Hypertrophy via Inhibiting Myocardial Inflammation

Frontiers in Pharmacology ◽

10.3389/fphar.2021.725186 ◽

2022 ◽

Vol 12 ◽

Author(s):

Yigang Zhong ◽

Liuying Chen ◽

Miaofu Li ◽

Lian Chen ◽

Yufeng Qian ◽

...

Keyword(s):

Signaling Pathway ◽

Cardiac Tissue ◽

Myocardial Hypertrophy ◽

Cell Model ◽

H9c2 Cell ◽

Myocardial Inflammation ◽

Cross Sectional ◽

Tnf Α

Myocardial hypertrophy plays an essential role in the structural remodeling of the heart and the progression to heart failure (HF). There is an urgent need to understand the mechanisms underlying cardiac hypertrophy and to develop treatments for early intervention. Dangshen Erling decoction (DSELD) is a clinically used formula in Chinese medicine for treating coronary heart disease in patients with HF. However, the mechanism by which DSELD produces its cardioprotective effects remains largely unknown. This study explored the effects of DSELD on myocardial hypotrophy both in vitro and in vivo. In vitro studies indicated that DSELD significantly (p < 0.05) reduced the cross-sectional area of the myocardium and reduced elevated lactate dehydrogenase (LDH), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 levels in the induced H9C2 cell model to study inflammation. In vivo experiments revealed that DSELD restores cardiac function and significantly reduces myocardial fibrosis in isoproterenol (ISO)-induced HF mouse model (p < 0.05). In addition, DSELD downregulated the expression of several inflammatory cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF), IL-1α, IL-1β, IL-3, IL-5, IL-7, IL-12, IL-13, and TNF-α in HF (p < 0.05). Further analysis of the cardiac tissue demonstrated that DSELD produces its anti-inflammatory effects via the Toll-like receptor (TLR)4 signaling pathway. The expression of TLR4 downstream proteins such as matrix metalloproteinase-9 (MMP9) and myeloid differentiation factor-88 (MyD88) was among the regulated targets. In conclusion, these observations suggest that DSELD exerts antihypertrophic effects by alleviating the inflammatory injury via the TLR4 signaling pathway in HF and thus holds promising therapeutic potentials.

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Aspiration Revisited: Prospective Evaluation of a Physiologically Pressurized Model With Animal Correlation and Broader Applicability to Filler Complications

Aesthetic Surgery Journal ◽

10.1093/asj/sjab194 ◽

2021 ◽

Author(s):

Hyoung-Jin Moon ◽

Won Lee ◽

Ji-Soo Kim ◽

Eun-Jung Yang ◽

Hema Sundaram

Keyword(s):

Normal Saline ◽

False Negative ◽

Vascular Complications ◽

Filler Injection ◽

Negative Results ◽

Needle Position ◽

False Negative Results ◽

In Vivo Testing

Abstract Background Aspiration testing before filler injection is controversial. Some believe that aspiration can help prevent inadvertent intravascular injection, while others cite false-negative results and question its value given that the needle position always changes somewhat during injection procedures. Objectives To test the relation of false-negative results to the viscosity of the material within the needle lumen and determine whether a less viscous material within the needle lumen could decrease the incidence of false-negative results. Methods In vitro aspiration tests were performed using 30-G and 27-G needle gauges, two cross-linked hyaluronic acid fillers, normal saline bags pressurized at 140 and 10 mmHg to mimic human arterial and venous pressures, and three needle lumen conditions (normal saline, air, and filler). Testing was repeated three times under each study condition (72 tests in total). For in vivo correlation, aspiration tests were performed on femoral arteries and central auricular veins in three rabbits (4–5 aspirations per site, 48 tests in total). Results In vitro and in vivo testing using 30-G needles containing filler both showed false-negative results on aspiration testing. In vitro and in vivo testing using needles containing saline or air showed positive findings. Conclusions False-negative results from aspiration testing may be reduced by pre-filling the needle lumen with saline rather than a filler. The pressurized system may help overcome challenges of animal models with intravascular pressures significantly different from those of humans. The adaptability of this system to mimic various vessel pressures may facilitate physiologically relevant studies of vascular complications.

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Effective decellularisation of human saphenous veins for biocompatible arterial tissue engineering applications: Bench optimisation and feasibility in vivo testing

Journal of Tissue Engineering ◽

10.1177/2041731420987529 ◽

2021 ◽

Vol 12 ◽

pp. 204173142098752

Author(s):

Nadiah S Sulaiman ◽

Andrew R Bond ◽

Vito D Bruno ◽

John Joseph ◽

Jason L Johnson ◽

...

Keyword(s):

Tissue Engineering ◽

Mechanical Strength ◽

Vascular Tissue ◽

Sodium Dodecyl ◽

Host Cells ◽

Replacement Model ◽

In Vivo Testing ◽

Vascular Scaffolds

Human saphenous vein (hSV) and synthetic grafts are commonly used conduits in vascular grafting, despite high failure rates. Decellularising hSVs (D-hSVs) to produce vascular scaffolds might be an effective alternative. We assessed the effectiveness of a detergent-based method using 0% to 1% sodium dodecyl sulphate (SDS) to decellularise hSV. Decellularisation effectiveness was measured in vitro by nuclear counting, DNA content, residual cell viability, extracellular matrix integrity and mechanical strength. Cytotoxicity was assessed on human and porcine cells. The most effective SDS concentration was used to prepare D-hSV grafts that underwent preliminary in vivo testing using a porcine carotid artery replacement model. Effective decellularisation was achieved with 0.01% SDS, and D-hSVs were biocompatible after seeding. In vivo xeno-transplantation confirmed excellent mechanical strength and biocompatibility with recruitment of host cells without mechanical failure, and a 50% patency rate at 4-weeks. We have developed a simple biocompatible methodology to effectively decellularise hSVs. This could enhance vascular tissue engineering toward future clinical applications.

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Occupational Exposure to Carbon Nanotubes and Carbon Nanofibres: More Than a Cobweb

Nanomaterials ◽

10.3390/nano11030745 ◽

2021 ◽

Vol 11 (3) ◽

pp. 745

Author(s):

Enrico Bergamaschi ◽

Giacomo Garzaro ◽

Georgia Wilson Jones ◽

Martina Buglisi ◽

Michele Caniglia ◽

...

Keyword(s):

Carbon Nanotubes ◽

Animal Studies ◽

Chemical Properties ◽

Biological Behavior ◽

Cross Sectional ◽

Carbon Nanofibres ◽

Material Entity ◽

Cross Sectional Design

Carbon nanotubes (CNTs) and carbon nanofibers (CNFs) are erroneously considered as singular material entities. Instead, they should be regarded as a heterogeneous class of materials bearing different properties eliciting peculiar biological outcomes both in vitro and in vivo. Given the pace at which the industrial production of CNTs/CNFs is increasing, it is becoming of utmost importance to acquire comprehensive knowledge regarding their biological activity and their hazardous effects in humans. Animal studies carried out by inhalation showed that some CNTs/CNFs species can cause deleterious effects such as inflammation and lung tissue remodeling. Their physico-chemical properties, biological behavior and biopersistence make them similar to asbestos fibers. Human studies suggest some mild effects in workers handling CNT/CNF. However, owing to their cross-sectional design, researchers have been as yet unable to firmly demonstrate a causal relationship between such an exposure and the observed effects. Estimation of acceptable exposure levels should warrant a proper risk management. The aim of this review is to challenge the conception of CNTs/CNFs as a single, unified material entity and prompt the establishment of standardized hazard and exposure assessment methodologies able to properly feeding risk assessment and management frameworks.

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Recapitulating Cardiac Structure and Function In Vitro from Simple to Complex Engineering

Micromachines ◽

10.3390/mi12040386 ◽

2021 ◽

Vol 12 (4) ◽

pp. 386

Author(s):

Ana Santos ◽

Yongjun Jang ◽

Inwoo Son ◽

Jongseong Kim ◽

Yongdoo Park

Keyword(s):

Tissue Engineering ◽

Extracellular Matrix ◽

Computational Modeling ◽

Cardiac Tissue ◽

Cardiac Development ◽

Heart Tissue ◽

Cardiac Tissue Engineering ◽

Cardiac Cells

Cardiac tissue engineering aims to generate in vivo-like functional tissue for the study of cardiac development, homeostasis, and regeneration. Since the heart is composed of various types of cells and extracellular matrix with a specific microenvironment, the fabrication of cardiac tissue in vitro requires integrating technologies of cardiac cells, biomaterials, fabrication, and computational modeling to model the complexity of heart tissue. Here, we review the recent progress of engineering techniques from simple to complex for fabricating matured cardiac tissue in vitro. Advancements in cardiomyocytes, extracellular matrix, geometry, and computational modeling will be discussed based on a technology perspective and their use for preparation of functional cardiac tissue. Since the heart is a very complex system at multiscale levels, an understanding of each technique and their interactions would be highly beneficial to the development of a fully functional heart in cardiac tissue engineering.

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DDEL-12. NANOPARTICLE DELIVERY OF DOXORUBICIN FOR THE TREATMENT OF DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)

Neuro-Oncology ◽

10.1093/neuonc/noaa222.047 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii286-iii286

Author(s):

Caitlin Ung ◽

Maria Tsoli ◽

Jie Liu ◽

Domenico Cassano ◽

Dannielle Upton ◽

...

Keyword(s):

Treatment Strategies ◽

Pediatric Brain Tumors ◽

Diffuse Intrinsic Pontine Glioma ◽

Confocal Imaging ◽

Cell Content ◽

Potent Effect ◽

Orthotopic Mouse Model ◽

In Vivo Testing

Abstract DIPGs are the most aggressive pediatric brain tumors. Currently, the only treatment is irradiation but due to its palliative nature patients die within 12 months. Effective delivery of chemotherapy across the blood-brain barrier (BBB) has been a key challenge for the eradication of this disease. We have developed a novel gold nanoparticle functionalised with human serum albumin (Au-NP, 98.8 ±19 nm) for the delivery of doxorubicin. In this study, we evaluated the cytotoxic efficacy of doxorubicin delivered through gold nanoparticles (Au-NP-Dox). We found that DIPG neurospheres were equally sensitive to doxorubicin and Au-NP-Dox (at equimolar concentration) by alamar blue assay. Colony formation assays demonstrated a significantly more potent effect of Au-NP-Dox compared to doxorubicin alone, while the Au-NP had no effect. Furthermore, western blot analysis indicated increased apoptotic markers cleaved Parp, caspase 3/7 and phosphorylated H2AX in Au-NP-Dox treated DIPG neurospheres. Live cell content and confocal imaging demonstrated significantly higher uptake of Au-NP-Dox compared to doxorubicin alone. Treatment of a DIPG orthotopic mouse model with Au-NP-Dox showed no signs of toxicity with stable weights being maintained during treatment. However, in contrast to the above in vitro findings the in vivo study showed no anti-tumor effect possibly due to poor penetration of Au-NP-Dox into the brain. We are currently evaluating whether efficacy can be improved using measures to open the BBB transiently. This study highlights the need for rigorous in vivo testing of new treatment strategies before clinical translation to reduce the risk of administration of ineffective treatments.

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In vitro and in vivo testing and correlation for oral controlled/ modified release dosage forms. report of the 2nd workshop held December 1988, Washington, DC. U.S.A.

Journal of Controlled Release ◽

10.1016/0168-3659(90)90064-z ◽

1990 ◽

Vol 14 (1) ◽

pp. 95-106 ◽

Cited By ~ 4

Author(s):

Jerome P. Skelly ◽

Gordon L. Amidon ◽

William H. Barr ◽

Leslie Z. Benet ◽

James E. Carter ◽

...

Keyword(s):

Dosage Forms ◽

Washington Dc ◽

Modified Release ◽

In Vivo Testing

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Rectus Femoris Mimicking Ultrasound Phantom for Muscle Mass Assessment: Design, Research, and Training Application

Journal of Clinical Medicine ◽

10.3390/jcm10122721 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2721

Author(s):

Nobuto Nakanishi ◽

Shigeaki Inoue ◽

Rie Tsutsumi ◽

Yusuke Akimoto ◽

Yuko Ono ◽

...

Keyword(s):

Measurement Accuracy ◽

Rectus Femoris ◽

Cross Sectional Area ◽

Sectional Area ◽

Cross Sectional ◽

Phantom Model ◽

Ultrasound Measurements ◽

Ultrasound Phantom

Ultrasound has become widely used as a means to measure the rectus femoris muscle in the acute and chronic phases of critical illness. Despite its noninvasiveness and accessibility, its accuracy highly depends on the skills of the technician. However, few ultrasound phantoms for the confirmation of its accuracy or to improve technical skills exist. In this study, the authors created a novel phantom model and used it for investigating the accuracy of measurements and for training. Study 1 investigated how various conditions affect ultrasound measurements such as thickness, cross-sectional area, and echogenicity. Study 2 investigated if the phantom can be used for the training of various health care providers in vitro and in vivo. Study 1 showed that thickness, cross-sectional area, and echogenicity were affected by probe compression strength, probe angle, phantom compression, and varying equipment. Study 2 in vitro showed that using the phantom for training improved the accuracy of the measurements taken within the phantom, and Study 2 in vivo showed the phantom training had a short-term effect on improving the measurement accuracy in a human volunteer. The new ultrasound phantom model revealed that various conditions affected ultrasound measurements, and phantom training improved the measurement accuracy.

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Coagulation under Mild Hypothermia Assessed by Thromboelastometry

Transfusion Medicine and Hemotherapy ◽

10.1159/000513922 ◽

2021 ◽

pp. 1-7

Author(s):

Tobias Nitschke ◽

Philipp Groene ◽

Alice-Christin Acevedo ◽

Tobias Kammerer ◽

Simon T. Schäfer

Keyword(s):

Mild Hypothermia ◽

Onset Time ◽

Rotational Thromboelastometry ◽

Lysis Time ◽

Sample Data ◽

In Vivo Testing ◽

Fibrinolytic Capacity ◽

Clot Formation Time

Introduction: While previous studies have shown a significant impact of extreme hypo- and hyperthermia on coagulation, effects of much more frequently occurring perioperative mild hypothermia are largely unknown. This study therefore aimed to analyze the effects of mild hypothermia using rotational thromboelastometry in vitro. Materials and Methods: Twelve healthy volunteers were included in this study. Standard thromboelastometric tests (EXTEM, INTEM, FIBTEM) were used to evaluate coagulation in vitro at 39, 37, 35.5, 35, and 33°C. Beyond standard thromboelastometric tests, we also evaluated the effects of mild hypothermia on the TPA-test (ClotPro, Enicor GmbH, Munich, Germany), a new test which aims to detect fibrinolytic capacity by adding tissue plasminogen activator to the sample. Data are presented as the median with 25/75th percentiles. Results: Extrinsically activated coagulation (measured by EXTEM) showed a significant increase in clot formation time (CFT; 37°C: 90 s [81/105] vs. 35°C: 109 s [99/126]; p = 0.0002), while maximum clot firmness (MCF) was not significantly reduced. Intrinsically activated coagulation (measured by INTEM) also showed a significant increase in CFT (37°C: 80 s [72/88] vs. 35°C: 94 s [86/109]; p = 0.0002) without significant effects on MCF. Mild hypothermia significantly increased both the lysis onset time (136 s [132/151; 37°C] vs. 162 s [141/228; 35°C], p = 0.0223) and lysis time (208 s [184/297; 37°C] vs. 249 s [215/358; 35°C]; p = 0.0259). Conclusion: This demonstrates that even under mild hypothermia coagulation is significantly altered in vitro. Perioperative temperature monitoring and management are greatly important and can help to prevent mild hypothermia and its adverse effects. Further investigation and in vivo testing of coagulation under mild hypothermia is needed.

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