scholarly journals Biomechanical simulations and 3D printing for endovascular device testing

2020 ◽  
Author(s):  
Michele Conti ◽  
Stefania Marconi ◽  
Ferdinando Auricchio
Keyword(s):  
3D Printing ◽  
Mechanical Response ◽  
Ex Vivo ◽  
Invasive Procedure ◽  
Patient Specific ◽  
Human Aorta ◽  
In Vitro Tests ◽  
Aortic Diseases ◽  
Endovascular Device

Endovascular aortic repair is a minimally invasive procedure to treat aortic diseases such as aneurysms and dissections. Thanks to technological advancements, such procedure has steadily shifted from the abdominal aorta towards the ascending part, i.e., near the heart, calling for an extensive and comprehensive benchmarking of (novel) endografts. Given such considerations, we have exploited porcine aorta with a pulse duplicator to analyse the mechanical interaction between the endovascular device and the native tissue. Our results have implications for using the porcine aorta as a model for human aorta in research. Particularly, the combination of in vitro tests performed using ex-vivo tissue, integrated validated patient-specific numerical simulations, mock arteries manufactured by 3D printing, can offer important insight on biomechanical impact of endograft design on post-operative aortic mechanical response.

scholarly journals Generation of vascular chimerism within donor organs

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shahar Cohen ◽  
Shirly Partouche ◽  
Michael Gurevich ◽  
Vladimir Tennak ◽  
Vadym Mezhybovsky ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Patient Specific ◽  
Machine Perfusion ◽  
Organ Perfusion ◽  
Perfusion Process ◽  
Hind Limbs ◽  
Porcine Organs ◽  
Immunological Barrier

AbstractWhole organ perfusion decellularization has been proposed as a promising method to generate non-immunogenic organs from allogeneic and xenogeneic donors. However, the ability to recellularize organ scaffolds with multiple patient-specific cells in a spatially controlled manner remains challenging. Here, we propose that replacing donor endothelial cells alone, while keeping the rest of the organ viable and functional, is more technically feasible, and may offer a significant shortcut in the efforts to engineer transplantable organs. Vascular decellularization was achieved ex vivo, under controlled machine perfusion conditions, in various rat and porcine organs, including the kidneys, liver, lungs, heart, aorta, hind limbs, and pancreas. In addition, vascular decellularization of selected organs was performed in situ, within the donor body, achieving better control over the perfusion process. Human placenta-derived endothelial progenitor cells (EPCs) were used as immunologically-acceptable human cells to repopulate the luminal surface of de-endothelialized aorta (in vitro), kidneys, lungs and hind limbs (ex vivo). This study provides evidence that artificially generating vascular chimerism is feasible and could potentially pave the way for crossing the immunological barrier to xenotransplantation, as well as reducing the immunological burden of allogeneic grafts.

scholarly journals 3D printed patient-specific aortic root models with internal sensors for minimally invasive applications

2020 ◽  
Vol 6 (35) ◽  
pp. eabb4641 ◽  
Author(s):  
Ghazaleh Haghiashtiani ◽  
Kaiyan Qiu ◽  
Jorge D. Zhingre Sanchez ◽  
Zachary J. Fuenning ◽  
Priya Nair ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Aortic Root ◽  
Three Dimensional ◽  
Sensor Arrays ◽  
Invasive Procedure ◽  
Patient Specific ◽  
Anatomical Site ◽  
Transcatheter Aortic Valve ◽  
Critical Regions

Minimally invasive surgeries have numerous advantages, yet complications may arise from limited knowledge about the anatomical site targeted for the delivery of therapy. Transcatheter aortic valve replacement (TAVR) is a minimally invasive procedure for treating aortic stenosis. Here, we demonstrate multimaterial three-dimensional printing of patient-specific soft aortic root models with internally integrated electronic sensor arrays that can augment testing for TAVR preprocedural planning. We evaluated the efficacies of the models by comparing their geometric fidelities with postoperative data from patients, as well as their in vitro hemodynamic performances in cases with and without leaflet calcifications. Furthermore, we demonstrated that internal sensor arrays can facilitate the optimization of bioprosthetic valve selections and in vitro placements via mapping of the pressures applied on the critical regions of the aortic anatomies. These models may pave exciting avenues for mitigating the risks of postoperative complications and facilitating the development of next-generation medical devices.

scholarly journals The Potential of CRISPR/Cas9 Gene Editing as a Treatment Strategy for Inherited Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Sameh A. Abdelnour ◽  
Long Xie ◽  
Abdallah A. Hassanin ◽  
Erwei Zuo ◽  
Yangqing Lu
Keyword(s):  
Therapeutic Potential ◽  
Ex Vivo ◽  
Genetic Diseases ◽  
Patient Specific ◽  
Innovative Technology ◽  
Rna Molecules ◽  
Inherited Diseases ◽  
Genomic Editing

Clustered regularly interspaced short palindromic repeats (CRISPR) is a promising innovative technology for genomic editing that offers scientists the chance to edit DNA structures and change gene function. It has several possible uses consisting of editing inherited deficiencies, treating, and reducing the spread of disorders. Recently, reports have demonstrated the creation of synthetic RNA molecules and supplying them alongside Cas9 into genome of eukaryotes, since distinct specific regions of the genome can be manipulated and targeted. The therapeutic potential of CRISPR/Cas9 technology is great, especially in gene therapy, in which a patient-specific mutation is genetically edited, or in the treating of human disorders that are untreatable with traditional treatments. This review focused on numerous, in vivo, in vitro, and ex vivo uses of the CRISPR/Cas9 technology in human inherited diseases, discovering the capability of this versatile in medicine and examining some of the main limitations for its upcoming use in patients. In addition to introducing a brief impression of the biology of the CRISPR/Cas9 scheme and its mechanisms, we presented the utmost recent progress in the uses of CRISPR/Cas9 technology in editing and treating of human genetic diseases.

Different Finite Element Strategies to Satisfy Clinical and Engineering Requirements in Modeling a Novel Percutaneous Device

2012 ◽  
Author(s):  
Claudio Capelli ◽  
Giovanni Biglino ◽  
Lorenza Petrini ◽  
Francesco Migliavacca ◽  
Philipp Bonhoeffer ◽  
...  
Keyword(s):  
Finite Element ◽  
Right Ventricular Outflow Tract ◽  
Patient Specific ◽  
In Vitro Tests ◽  
Loading Conditions ◽  
Modeling Tools ◽  
Transcatheter Heart Valve ◽  
Specific Loading ◽  
Valve Implantation

By taking into account patient-specific properties, finite element (FE) models can aid in the optimization of the devices’ mechanical performances, accelerating the time of development and reducing testing costs. Patient-specific cardiovascular modeling can also drive the development of novel devices [1], by means of anatomical elements that are more representative than animal surrogates [2], and integrating standard in vitro tests with patient-specific loading conditions [3]. Transcatheter heart valve implantation can particularly benefit from a modeling approach. In the field of treatment of valve dysfunctions, percutaneous techniques are relatively new or under development, and modeling tools can contribute to improve these procedures (e.g. design modifications or different routes for device insertion) and increase patient safety in the early introduction of new devices into clinical practice. For a feasible clinical application, computational methods need to be fully validated against physical data, to take into account patient-specific properties, and to provide results in a short time. Instead, from an engineering perspective, models can cost-effectively aid the design phase by improving preclinical testing with more realistic loading conditions for accurate simulation of mechanical behaviour and prediction of durability. This study aims to identify optimal modeling strategies to respond to both clinical and engineering requirements. As a case study, simulations were conducted on a new percutaneous pulmonary valve implantation (PPVI) device [4] tested within a patient-specific right ventricular outflow tract model.

Living the heart in three dimensions: applications of 3D printing in CHD

2019 ◽  
Vol 29 (06) ◽  
pp. 733-743 ◽  
Author(s):  
Mari Nieves Velasco Forte ◽  
Tarique Hussain ◽  
Arno Roest ◽  
Gorka Gomez ◽  
Monique Jongbloed ◽  
...  
Keyword(s):  
3D Printing ◽  
Heart Surgery ◽  
Wide Spectrum ◽  
Three Dimensional ◽  
Structural Heart Disease ◽  
Medical Personnel ◽  
Three Dimensions ◽  
Patient Specific ◽  
3D Printed

AbstractAdvances in biomedical engineering have led to three-dimensional (3D)-printed models being used for a broad range of different applications. Teaching medical personnel, communicating with patients and relatives, planning complex heart surgery, or designing new techniques for repair of CHD via cardiac catheterisation are now options available using patient-specific 3D-printed models. The management of CHD can be challenging owing to the wide spectrum of morphological conditions and the differences between patients. Direct visualisation and manipulation of the patients’ individual anatomy has opened new horizons in personalised treatment, providing the possibility of performing the whole procedure in vitro beforehand, thus anticipating complications and possible outcomes. In this review, we discuss the workflow to implement 3D printing in clinical practice, the imaging modalities used for anatomical segmentation, the applications of this emerging technique in patients with structural heart disease, and its limitations and future directions.

scholarly journals Two-Photon Polymerisation 3D Printing of Microneedle Array Templates with Versatile Designs: Application in the Development of Polymeric Drug Delivery Systems

2020 ◽  
Vol 37 (9) ◽  
Author(s):  
Ana Sara Cordeiro ◽  
Ismaiel A. Tekko ◽  
Mohamed H. Jomaa ◽  
Lalitkumar Vora ◽  
Emma McAlister ◽  
...  
Keyword(s):  
Drug Delivery ◽  
3D Printing ◽  
Flexible Manufacturing ◽  
Ex Vivo ◽  
Low Cost ◽  
Insertion Depth ◽  
Two Photon ◽  
Polymeric Drug Delivery ◽  
Polymeric Drug Delivery Systems

Abstract Purpose To apply a simple and flexible manufacturing technique, two-photon polymerisation (2PP), to the fabrication of microneedle (MN) array templates with high precision and low cost in a short time. Methods Seven different MN array templates were produced by 2PP 3D printing, varying needle height (900–1300 μm), shape (conical, pyramidal, cross-shaped and with pedestal), base width (300–500 μm) and interspacing (100–500 μm). Silicone MN array moulds were fabricated from these templates and used to produce dissolving and hydrogel-forming MN arrays. These polymeric MN arrays were evaluated for their insertion in skin models and their ability to deliver model drugs (cabotegravir sodium and ibuprofen sodium) to viable layers of the skin (ex vivo and in vitro) for subsequent controlled release and/or absorption. Results The various templates obtained with 2PP 3D printing allowed the reproducible fabrication of multiple MN array moulds. The polymeric MN arrays produced were efficiently inserted into two different skin models, with sharp conical and pyramidal needles showing the highest insertion depth values (64–90% of needle height). These results correlated generally with ex vivo and in vitro drug delivery results, where the same designs showed higher drug delivery rates after 24 h of application. Conclusion This work highlights the benefits of using 2PP 3D printing to prototype variable MN array designs in a simple and reproducible manner, for their application in drug delivery.

Hypotensive effects of the triterpene oleanolic acid for cardiovascular prevention

2020 ◽  
Vol 13 ◽  
Author(s):  
A. Sureda ◽  
M. Monserrat-Mesquida ◽  
S. Pinya ◽  
P. Ferriol ◽  
S. Tejada
Keyword(s):  
Blood Pressure ◽  
Oleanolic Acid ◽  
Ex Vivo ◽  
Biological Activities ◽  
Cardiovascular Prevention ◽  
In Vivo Studies ◽  
Antihypertensive Activity ◽  
In Vitro Tests

Background:: Hypertension is a high prevalent chronic disease worldwide and a major cardiovascular risk factor. Oleanolic acid (3β-hydroxy-olea-12-en-28-oic acid) is a wide distributed bioactive pentacyclic triterpenoid with diverse biological activities such as anti-inflammatory, hepaprotective anti-diabetic or anti-hypertensive. Objective:: The aim of this study was to review and highlight the available data about antihypertensive activity of oleanolic acid and the described mechanisms of action. Method:: Extensive searches were made in the available literature on oleanolic acid and the data investigating its antihypertensive effects were analysed. Results:: Most of research has been performed on animal models of hypertension, ex vivo studies with aortic ring and some in vitro tests with cell cultures, whereas clinical trials are still lacking. Treatment of hypertensive animals with oleanolic acid significantly ameliorated the rise in the systolic blood pressure. In addition, the hypotensive effects of oleanolic acid are also related to a potent diuretic-natriuretic activity and nephroprotection. In vitro studies have characterized the participation of various signalling pathways that modulate the release of vasodilation mediators. Conclusion:: In vitro and in vivo studies suggest that oleanolic acid effectively reduce blood pressure and could be an interesting co-adjuvant to conventional treatment of hypertension.

Abstract 17031: Noninvasive CT-Based Hemodynamic Assessment Using 3D Printing and Virtual Functional Assessment Index

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kranthi K Kolli ◽  
Abdul Zahid ◽  
Alexandre Caprio ◽  
Patricia Xu ◽  
Robert Shepherd ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Pressure Drop ◽  
3D Printing ◽  
Functional Assessment ◽  
Patient Specific ◽  
Fractional Flow ◽  
Flow Rates ◽  
Assessment Index ◽  
3D Printed

Background: Virtual functional assessment index (vFAI), an alternative approach for assessing hemodynamic significance of stenosis has been shown to enhance the diagnostic performance of coronary computed tomography angiography (CCTA) based on evaluating the area under pressure drop-flow curve for a stenosis. Previously, this was assessed via computational fluid dynamics. We investigated the evaluation of vFAI from CCTA images using 3D printing and an in vitro flow loop and its efficacy as compared to the invasively measured fractional flow reserve (FFR). Methods and Results: Eighteen patients with varying degrees of coronary artery disease who underwent non-invasive CCTA scans and invasive FFR of their left anterior descending coronary artery (LAD) were included. The LAD artery was segmented and reconstructed using Mimics (Materialise inc.,). The segmented models were then 3D printed using Carbon 3D printer (Carbon Inc.,) with rigid resins. An in vitro flow circulation system representative of invasive measurements in a cardiac catheterization laboratory was developed to experimentally evaluate the hemodynamic parameters of pressure and flow (Fig A). For each model, a range of physiological flow rates was applied by a peristaltic steady flow pump and titrated by a flow sensor. The pressure drop and the pressure ratio (Pd/Pa) were assessed for patient-specific aortic pressure and differing flow rates. vFAI was evaluated as the normalized area under the P d /P a vs Q curve from 0 to 240 mL/min. There was a strong correlation between vFAI and FFR, (R = 0.83, p < 0.001; Fig B) and a very good agreement between the two parameters by Bland-Altman analysis. The mean difference of measurements from the two methods was 0.06 (SD = 0.08, p=0.0063; Fig C), indicating a small systematic overestimation of the FFR by vFAI. Conclusions: vFAI can be effectively derived from 3D CTCA datasets using 3D-printed in vitro models, based on evaluation over a range of hemodynamic conditions.

Abstract WP1: High-Frequency Optical Coherence Tomography for Cerebrovascular Disease

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Ajit S Puri ◽  
Giovanni Ughi ◽  
Robert M King ◽  
Matthew Gounis
Keyword(s):  
Optical Coherence Tomography ◽  
Cerebrovascular Disease ◽  
High Frequency ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Image Resolution ◽  
Patient Specific ◽  
Optical Coherence

Introduction: Optical coherence tomography (OCT) has played an important role in the diagnosis and treatment guidance in coronary artery disease. However, existing OCT systems are not suitable for routine neurovascular applications due to the size and tortuosity of the arteries. Hypothesis: We seek to demonstrate a prototype high-frequency OCT (HF-OCT) capable of high-resolution imaging in simulated cerebrovascular anatomy. Methods: A low-profile HF-OCT system was constructed with an image resolution approaching 10μm. Using an in vitro, patient-specific model of the circle of Willis with circulating porcine blood, we characterized the delivery of the device and ability to image in a tortuous path. Also, human cadaver intracranial atherosclerosis plaques were imaged with HF-OCT and assessed by an expert imager. Finally, neurovascular devices were implanted in 8 pigs (Fig 1) and HF-OCT imaging was compared with gold-standard DSA and CT. Results: In the phantom, optimal blood clearance was achieved through an intermediate catheter (5 Fr Navien) with infusion of contrast at 5 ml/s in the internal carotid and basilar artery, and 3 ml/sec in the MCA. The in vivo study demonstrated that both malapposition of devices or thrombus formation along the device surface could be reliably diagnosed among 3 reviewers (Fleiss’s kappa of 0.87 and 0.9, respectively). This agreement was superior to DSA and CT. Imaging in tortuous swine brachial showed in all cases imaging free of artifacts, uniform illumination and ability to visualize vessel wall layers. Plaque types including ‘lipid pools’, fibrotic, and calcific tissue from cadaver specimens of ICAD could be adequately depicted by HF-OCT. Conclusion: In vitro, in vivo and ex vivo characterization of a novel HF-OCT device has shown it is capable of imaging in the tortuous intracranial vascular anatomy. This technology has to potential to aid in the diagnosis of cerebrovascular disease and guide optimal endovascular treatment.

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