3D Bioprinting The Heart & Cardiovascular System

Category: Blog,From Academia
blank blank Nov 02, 2020

From Academia” features recent, relevant, close to commercialization academic publications in the space of healthcare 3D printing, 3D bioprinting, and related emerging technologies. In this issue, we included three recent publications all focusing on 3D bioprinting the heart. The first article is a review article overviewing recent progress on attempts to reconstruct the heart and heart tissues for various applications. The second is a now well-circulated paper from Adam Feinberg’s group on FRESH 3D bioprint a full-size heart. The final article showcase creative ways to scale bioprinting using multi-material projection-based stereolithography with a sacrificial bioink.

Email: Rance Tino (tino.rance@gmail.com) if you want to pen an Expert Corner blog for us or want to share relevant academic publications with us.

Recent Applications of Three Dimensional Printing in Cardiovascular Medicine

Authored by Chiara Gardin, Letizia Ferroni, Christian Latremouille, Juan Carlos Chachques, Dinko Mitrečić and Barbara Zavan, Cells. 17 March 2020

Cardiovascular 3D printing workflow includes acquisition of imaging data, segmentation, imaging modeling, and actual 3D printing. Reprinted with permission from Vukicevic et al. [12]. Copyright. Cells
Cardiovascular 3D printing workflow includes the acquisition of imaging data, segmentation, imaging modeling, and actual 3D printing. Reprinted with permission from
Vukicevic et al. [12]. Copyright. Cells

Example of 3D bioprinting of heart valve conduit with encapsulation of human aortic VICs (HAVICs) within the leaflets. Copyright. Cells
Example of 3D bioprinting of heart valve conduit with encapsulation of human aortic VICs (HAVICs) within the leaflets. Copyright. Cells

Abstract: 

Three dimensional (3D) printing, which consists of the conversion of digital images into a 3D physical model, is a promising and versatile field that, over the last decade, has experienced rapid development in medicine. Cardiovascular medicine, in particular, is one of the fastest-growing areas for medical 3D printing.

In this review, we firstly describe the major steps and the most common technologies used in the 3D printing process, then we present current applications of 3D printing with relevance to the cardiovascular field. The technology is more frequently used for the creation of anatomical 3D models useful for teaching, training, and procedural planning of complex surgical cases, as well as for facilitating communication with patients and their families.

However, the most attractive and novel application of 3D printing in the last years is bioprinting, which holds the great potential to solve the ever-increasing crisis of organ shortage. In this review, we then present some of the 3D bioprinting strategies used for fabricating fully functional cardiovascular tissues, including myocardium, heart tissue patches, and heart valves.

The implications of 3D bioprinting in drug discovery, development, and delivery systems are also briefly discussed, in terms of in vitro cardiovascular drug toxicity. Finally, we describe some applications of 3D printing in the development and testing of cardiovascular medical devices, and the current regulatory frameworks that apply to the manufacturing and commercialization of 3D printed products.

FRESH 3D Bioprinting a Full-Size Model of the Human Heart

Authored by Eman Mirdamadi, Joshua W. Tashman, Daniel J. Shiwarski, Rachelle N. Palchesko, and Adam W. Feinberg. ACS Biomaterials Science & Engineering, 23 October 2020

Printing a full-size model of the adult human heart using alginate. (A) Three-dimensional CAD model of an adult human heart based on an MRI scan (BodyParts3D). (B) CAD model is processed in Meshmixer to ensure all regions of interest are printable. (C) G-code pathing rendered in 3D of the heart. (D) Full-size heart FRESH printed using alginate. (E) Alginate heart stained with a 0.1% (w/v) Alizarin red floating in an aqueous solution with a 1.5″ long printing needle in the foreground for scale. (F) Alginate heart (not stained) removed from the solution and handled I air to show that the model deforms similar to a real heart. (G) Half print of the alginate heart done to show the internal structure (scale bar = 1.5 cm). (H) Pulmonary and (I) aortic valves printed inside the heart model (scale bar = 1 cm). (J) Papillary muscle and (K) trabeculae carnae printed inside the heart model (scale bar = 1 cm). Copyright. ACS Biomaterials Science & Engineering
Printing a full-size model of the adult human heart using alginate. (A) Three-dimensional CAD model of an adult human heart based on an MRI scan (BodyParts3D). (B) CAD model is processed in Meshmixer to ensure all regions of interest are printable. (C) G-code pathing rendered in 3D of the heart. (D) Full-size heart FRESH printed using alginate. (E) Alginate heart stained with a 0.1% (w/v) Alizarin red floating in an aqueous solution with a 1.5″ long printing needle in the foreground for scale. (F) Alginate heart (not stained) removed from the solution and handled I air to show that the model deforms similarly to a real heart (Video below). (G) Half print of the alginate heart done to show the internal structure (scale bar = 1.5 cm). (H) Pulmonary and (I) aortic valves printed inside the heart model (scale bar = 1 cm). (J) Papillary muscle and (K) trabeculae carnae printed inside the heart model (scale bar = 1 cm).
Copyright. ACS Biomaterials Science & Engineering

Abstract: 

Recent advances in embedded three-dimensional (3D) bioprinting have expanded the design space for fabricating geometrically complex tissue scaffolds using hydrogels with mechanical properties comparable to native tissues and organs in the human body.

The advantage of approaches such as Freeform Reversible Embedding of Suspended Hydrogels (FRESH) printing is the ability to embed soft biomaterials in a thermoreversible support bath at sizes ranging from a few millimeters to centimeters. In this study, we were able to expand this printable size range by FRESH bioprinting a full-size model of an adult human heart from patient-derived magnetic resonance imaging (MRI) data sets.

We used alginate as the printing biomaterial to mimic the elastic modulus of cardiac tissue. In addition to achieving high print fidelity on a low-cost printer platform, FRESH-printed alginate proved to create mechanically tunable and suturable models. This demonstrates that large-scale 3D bioprinting of soft hydrogels is possible using FRESH and that cardiac tissue constructs can be produced with potential future applications in surgical training and planning.

Printing a perfusable, full-size segment of the coronary artery. (A) Three-dimensional model of the human heart is segmented to isolate a region of a coronary artery superimposed on the left ventricle wall. (B) Coronary artery in the image file was further processed and scaled in size by 2× to make the artery lumen hollow and patent. (C) Coronary artery segment 3D FRESH printed in alginate with a needle inserted at the proximal end. (D) Coronary artery segment after perfusion with red glycerol, demonstrating patency through the bifurcation. Copyright. ACS Biomaterials Science & Engineering
Printing a perfusable, full-size segment of the coronary artery. (A) Three-dimensional model of the human heart is segmented to isolate a region of a coronary artery superimposed on the left ventricle wall. (B) Coronary artery in the image file was further processed and scaled in size by 2× to make the artery lumen hollow and patent. (C) Coronary artery segment 3D FRESH printed in alginate with a needle inserted at the proximal end. (D) Coronary artery segment after perfusion with red glycerol, demonstrating patency through the bifurcation. Copyright. ACS Biomaterials Science & Engineering

Vascular bioprinting with enzymatically degradable bioinks via multi-material projection-based stereolithography

Authored by Alexander Thomas, Isabel Orellanoc, Tobias Lam, Benjamin Noichl, Michel-Andreas Geiger, Anna Klara Amler, Anna Elisabeth Kreuder, Christopher Palmer, Georg Duda, Roland Lauster, Lutz Kloke. Acta Biomaterialia. 24 September 2020

Bioprinting of vascular constructs. (a) CAD model of vascular construct. (b) Vascular construct directly after bioprinting (left), after 3 hours (middle) and after 40 hours (right). Scale bar indicates 1000 µm. (c) Close-up of released, attaching GFP-HUVECs 3 hours post-print. Scale bar indicates 200 µm. (d) Sectional views on a printed channel lined with GFP-HUVECs (green) expressing CD31 (red) on day 28. Scale bar indicates 200 µm. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.). Copyright. Acta Biomaterialia
Bioprinting of vascular constructs. (a) CAD model of the vascular construct. (b) Vascular construct directly after bioprinting (left), after 3 hours (middle), and after 40 hours (right). Scale bar indicates 1000 µm. (c) Close-up of released, attaching GFP-HUVECs 3 hours post-print. Scale bar indicates 200 µm. (d) Sectional views on a printed channel lined with GFP-HUVECs (green) expressing CD31 (red) on day 28. Scale bar indicates 200 µm. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.). Copyright. Acta Biomaterialia

Abstract

The introduction of cavities and channels into 3D bioprinted constructs is a prerequisite for recreating physiological tissue architectures and integrating vasculature. Projection-based stereolithography inherently offers high printing speed with high spatial resolution, but so far has been incapable of fabricating complex native tissue architectures with cellular and biomaterial diversity. The use of sacrificial photo inks, i.e. photopolymerizable biomaterials that can be removed after printing, theoretically allows for the creation of any construct geometry via a multi-material printing process. However, the realization of this strategy has been challenging because of difficult technical implementation and a lack of performant biomaterials. In this work, we use our projection-based, multi-material stereolithographic bioprinter, and an enzymatically degradable sacrificial photoink to overcome the current hurdles. Multiple, hyaluronic acid-based photoinks were screened for printability, mechanical properties and digestibility through hyaluronidase. A formulation meets all major requirements, i.e. desirable printing properties, generation of sufficiently strong hydrogels, as well as fast digestion rate, was identified. The biocompatibility of the material system was confirmed by the embedding of human umbilical vein endothelial cells with the followed enzymatic release. As a proof-of-concept, we bioprinted vascular models containing perfusable, endothelial cell-lined channels that remained stable for 28 days in culture. Our work establishes digestible sacrificial biomaterials as a new material strategy for 3D bioprinting of complex tissue models.

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