3D Printing for Congenital Heart Disease and Drug Toxicity

Category: Blog,From Academia
blank blank Nov 15, 2020

In this issue, we included three latest publications focusing on 3D printing for congenital heart disease and a novel organ on a chip model focusing on cardiac toxicity. The first two articles focus on how 3D printed models based on 3D echocardiogram datasets can be useful in intervention or treatment planning for congenital heart disease. The third article demonstrates the potential feasibility of using an organ-on-a-chip model combining breast cancer and cardiac cells to monitor breast cancer treatment and associated cardiac toxicity/side effects from chemotherapy. “From Academia” features recent, relevant, close to commercialization academic publications. Subjects include but not limited to healthcare 3D printing, 3D bioprinting, and related emerging technologies.

Email: Rance Tino (tino.rance@gmail.com) if you want to share relevant academic publications with us.

3D printing applications for percutaneous structural interventions in congenital heart disease

– Authored by Hannah Tredway, Nikhil Pasumarti, Matthew A. Crystal, Kanwal M. Farooqi. Mini-invasive Surgery. 6 November 2020

3D Printing for Congenital Heart Disease
3D DynaCT reconstruction and 3D printed models: pre-Melody valve implantation in the RVOT (A, C); and post-Melody valve implantation in the RVOT (B, D). Reprinted with permission from Poterucha et al. 3D: three-dimensional; RVOT: right ventricular outflow tract. Copyright Mini-invasive Surgery.

Abstract: 

The past several decades have seen remarkable advancements in percutaneous interventions for the treatment of congenital heart disease (CHD). These advancements have been significantly aided by improvements in noninvasive diagnostic imaging. The use of three-dimensional (3D) printed models for planning and simulation of catheter-based procedures has been demonstrated for numerous cardiac defects and has been shown to reduce complications, procedure times, and limit radiation exposure. This paper reviews the process by which patient-specific 3D cardiac models are produced, as well as numerous applications of these models for use in percutaneous interventions in CHD.

3D Printing for Congenital Heart Disease
Echocardiography-based 3D printing of patient-specific models. Segmentation of LAA (shaded area) from 3D TEE data (A, D) is turned into a digital object (B, E), and printed using tissue-mimicking material (C, F). The major and minor ostial diameters and depth of the LAA are measured. Arrows denote pulmonary vein ridge; stars denote appendicular trabeculations. Closure devices are then sized and placed within the 3D model (G-I), and device compression and (H) protrusion are measured using a digital caliper. Device stability is assessed using the tug-test (I). Device placement visualized on TEE (J-L), and color Doppler assessment showing no peri-device leak (M). Reprinted with permission from Fan et al. Copyright Mini-invasive Surgery.

3D Echocardiography Provides Highly Accurate 3D Printed Models in Congenital Heart Disease

– Authored by K. L. Mowers, J. B. Fullerton, D. Hicks, G. K. Singh, M. C. Johnson & S. Anwar. Pediatric Cardiology. 20 October 2020

3D Printing for Congenital Heart Disease
Illustration of the process to segment 3D echocardiographic images. Three-dimensional echocardiographic data of a patient with an unrepaired atrioventricular septal defect with a common AV valve. Copyright. Pediatric Cardiology

Abstract: 

Cardiac 3D printing is mainly performed from magnetic resonance imaging (MRI) and computed tomography (CT) 3D datasets, though anatomic detail of atrioventricular (AV) valves may be limited. 3D echo provides excellent visualization of AV valves. Thus, we tested the feasibility and accuracy of 3D printing from 3D echo in this pilot series of subjects with congenital heart disease (CHD), with a focus on valve anatomy.

Five subjects with CHD were identified. 3D echo data were converted to 3D printable files and printed in collaboration with 3D Systems Healthcare (Golden, Colorado). A novel technique for valve modeling was utilized using commercially available software.

Two readers (KM, SA) independently measured valve structures from 3D models and compared them to source echo images. 3D printing was feasible for all cases. Table 1 shows measurements comparing 2D echo to 3D models. Bland Altman analysis showed close agreement and no significant bias between 2D and digital 3D models (mean difference 0.0, 95% CI 1.1 to − 1.1) or 2D vs printed 3D models, though with wider limits of agreement (mean difference − 0.3, 95% CI 1.9 to − 2.6). The accuracy of 3D models compared to 2D was within < 0.5 mm.

This pilot study shows 3D echo datasets can be used to reliably print AV and semilunar valve structures in CHD. The 3D models are highly accurate compared to the source echo images. This is a novel and value-added technique that adds incremental information on cardiac anatomy over current methods.

3D Printing for congenital heart disease
Two-dimensional echocardiographic (apical 4 chamber view) measurements of the common AV valve left AV valve and right AV valve planes for Case 2—a patient with complete common AV canal (top panel). Corresponding measurements from digital 3D model (middle panel) and printed 3D model are shown in the bottom pane. Copyright. Pediatric Cardiology

A Heart‐Breast Cancer‐on‐a‐Chip Platform for Disease Modeling and Monitoring of Cardiotoxicity Induced by Cancer Chemotherapy

– Authored by Junmin Lee  Shreya Mehrotra  Elaheh Zare‐Eelanjegh  Raquel O. Rodrigues  Alireza Akbarinejad  David Ge  Luca Amato  Kiavash Kiaee  YongCong Fang  Aliza Rosenkranz  Wendy Keung  Biman B. Mandal  Ronald A. Li  Ting Zhang  HeaYeon Lee  Mehmet Remzi Dokmeci  Yu Shrike Zhang  Ali Khademhosseini  Su Ryon Shin, Small. 23 October 2020 

Organ on a chip for drug toxicity
Design of the cardiac-breast cancer-on-a-chip platform with the EC immuno-aptasensing system using multiplexed microelectrode array. a) Schematic illustrating the development of healthy and disease cardiac model on chip for addressing the induced cardiotoxicity as a result of BC chemotherapy. b) A photograph of the fabricated microfluidic device having iPSC-derived cardiac tissues and BC tissues. c) Schematic illustration of the integrated cardiac-breast cancer-on-a-chip platform with the EC immuno-aptasensing system using aptamers-functionalized biosensors on microelectrodes. Scale bars: 2 cm. Copyright. Small

Abstract: 

Cardiotoxicity is one of the most serious side effects of cancer chemotherapy. Current approaches to monitoring of chemotherapy-induced cardiotoxicity (CIC) as well as model systems that develop in vivo or in vitro CIC platforms fail to notice early signs of CIC. Moreover, breast cancer (BC) patients with pre-existing cardiac dysfunctions may lead to different incident levels of CIC. Here, a model is presented for investigating CIC where not only induced pluripotent stem cell (iPSC)-derived cardiac tissues are interacted with BC tissues on a dual-organ platform, but electrochemical immuno-aptasensors can also monitor cell secreted multiple biomarkers.

Fibrotic stages of iPSC-derived cardiac tissues are promoted with a supplement of transforming growth factor-β1 to assess the differential functionality in healthy and fibrotic cardiac tissues after treatment with doxorubicin (DOX). The production trend of biomarkers evaluated by using the immuno-aptasensors well-matches the outcomes from conventional enzyme-linked immunosorbent assay, demonstrating the accuracy of the authors’ sensing platform with much higher sensitivity and lower detection limits for early monitoring of CIC and BC progression. Furthermore, the versatility of this platform is demonstrated by applying a nanoparticle-based DOX-delivery system. The proposed platform would potentially help allow early detection and prediction of CIC in individual patients in the future.

Organ on a chip for drug toxicity
Application of our cardiac-breast cancer-on-a-chip platform for further studying cardiotoxicity with NP-based drug delivery system. a) Schematic of the procedure to generate GYSM-NP-DOX. b) Representative immunofluorescence images of live/dead staining for iPSC-derived healthy or fibrotic cardiac and BC tissues after 6 days in culture with a supplement of free DOX or NP-conjugated DOX. Cytotoxicity quantification of free DOX, NPs, and NP+DOX on c) cardiac and d) BC cells for 5 days in culture using Prestoblue (N = 4). EC measurement of e) Troponin T, f) CK-MB, and g) HER-2 rate in the cardiac-breast cancer-on-a-chip with a supplement of free DOX or NP-conjugated DOX (N = 3). (One-way ANOVA with Tukey significant difference post hoc test; *p < 0.05, **p < 0.005, and ***p < 0.0005). Error bars represent standard deviation. Copyright. Small

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