A Call to the Heart-A Perspective on the State of 3D Bioprinting of Cardiac Tissue

3D Bioprinting is actively being utilized in a wide variety of tissue applications as both the enabling technology and the science behind the bioinks or biomaterials are continually advancing.  Cardiovascular tissue in-particular has been of interest to many tissue engineering groups, making recent headlines likely because cardiac-related disease (namely ischemic disease) remains the number one cause of mortality around the globe according to the World Health Organization. 

 Basic research in the field of cardiovascular regenerative medicine has historically been primarily focused on the molecular and cellular-driven aspects of the recovery process after ischemic injury in order to determine optimal therapeutic agents to apply to the injured tissue area, but with the advent of 3D bioprinting, the concept of either replacing the damaged tissue with a patch or to alleviate heart failure with the replacement of a whole new organ is becoming a reality. 

The investigation into how cardiac tissue could be fabricated has led to discovering ways to fabricate valve constructs in order to improve-upon the synthetic valve replacements that are currently in practice. Before the advent of the availability of 3D printing-based approaches, valves were fabricated using injection molding, a technique common to many standard fabrication strategies. However, molding was extremely limited in terms of incorporating the inherent complex structure and material composition of valve tissue.  3D bioprinting of valve constructs enabled the composition heterogeneity necessary in valve function and resulted in cell viability for up to 21 days by also utilizing more native-like extracellular matrix materials as a support structure. Specifically, in the context of valve tissue, it is not as simple as determine support materials that assist in viability, but also determining materials that allowing the cells to exert the mechanical forces and or changes to their environment this is part of their function in the native heart valve (i.e. Hockaday et al 2012; Duan et al 2014). While these studies approached the physiological size of human valve tissue, validation on the function of these constructs had not yet been completed. The extensive research on just a component of this organ system illustrates the overall complexity of heart tissue in the context of biofabrication.

 In addition to the flow regulation and thereby mechanical properties of valve tissue that is required for normal function, the fabrication of the whole heart tissue has unique considerations that need to be kept in-mind for clinical applications.  A unique aspect to cardiac tissue is the fact it is not only a tissue comprised of cells and extracellular matrix but is also driven by electromechanical forces, and these forces need to be synchronized with the host tissue for proper function to occur (Huang et al 2018). The determination of optimal materials for cardiac tissue fabrication has been investigated and reviewed by others (Serpooshan et al 2018).  The recapitulation of the form of the total heart structure is an active topic of research and discussion as evidenced by the recently published work from Carnegie-Mellon University. In this work, the researchers conducted functional testing on the to-scale cardiac tissue that was fabricated (Feinberg et al 2019). The material composition and integrated fabrication strategy that Feinberg and colleagues developed and is described in this article is part of the offering at FluidForm. Other companies such as BioLife4D has also made public their commitment to making a whole human heart. Advanced Solutions Life Sciences, is making strides in generating vascularizing strategies for 3D tissue constructs, as well as providing the only 6-axis robotic arm based bioprinter technology which can print onto a contoured surface and is altogether well-suited to execute the fabrication strategies previously described. 

Personally, having a background in cardiac tissue regeneration, the excitement, and innovation around methodologies to alleviate ischemic heart disease is very exciting to witness and be a part of.  All this recent attention in the cardiac tissue space begs the question- what will be the first human organ system made via 3D bioprinting? 

References:

Hockaday, L; Kang, K; Colangelo, N; Cheung, P; Duan, B; Malone, E; Wu, J; Girardi, L; Bonassar, L; Lipson, H; Chu, C; Butcher, J. Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds. Biofabrication. 2012, 4(3): 035005

Duan, B; Hockaday, L; Kang, K; Butcher, J. 3D Bioprinting of Heterogeneous Aortic Valve Conduits with Alginate/Gelatin Hydrogels. J Biomed Mater Res A. 2014, 101(5): 1255–1264

Huang, N; Serpooshan V; Morris, V; Sayed, N, Pardon, G; Abilez, O; Nakayama, K; Pruitt, B; Wu, S; Yoon, Y; Zhang, J; Wu, J. Nature Communications Biology. 2018, 1:199 

Serpooshan, V; Mahmoudi, M; Hu, D; Hu, J; Wu, S. Bioengineering cardiac constructs using 3D printing. Journal of 3D Printing in Medicine.  2018, 1(2): 123-139

Lee, A; Hudson, A; D. Shiwarski, D; Tashman, J; Hinton, Yerneni, S; Bliley, J; Campbell, Feinberg, A. 3D bioprinting of collagen to rebuild components of the human heart. Science. 2019,365: 482–487.

About the Author:

Dr. Lehanna Sanders is a cellular and molecular biologist and has done research within the field of regenerative medicine for 8 years.  She received her Bachelor’s degree in Cellular, Molecular, and Development Biology from Purdue University where she completed an honors thesis project in Biomedical Engineering.  She then completed her PhD at Vanderbilt  University where she published work in the area of molecular repair processes following acute cardiac injury.  During her time at Vanderbilt, she served on the Skills Development Committee for the NHLBI Progenitor Cell Biology Consortium, as well as a member of the Board of the Directors for the Life Science Tennessee-Academic Alliance.  She now works in Business Development for Advanced Solutions Life Sciences, where she is continuing to grow the field of regenerative biology through working closely with scientists and engineers to advance innovations in 3D bioprinting and biofabrication.

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