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Novel 3D Bioprinting Approach Generates Vascularized and Well-organized Cardiac Tissue Constructs

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Review of “A multi-cellular 3D bioprinting approach for vascularized heart tissue engineering based on HUVECs and iPSC-derived cardiomyocytes” from Scientific Reports by Stuart P. Atkinson 

While generating transplantable somatic cell types from pluripotent stem cell sources remains a difficult task, recapitulating the inherent complexity required of engineered 3D tissue constructs with tailored biological and mechanical properties also represents a significant challenge to the field. However, 3D bioprinting has emerged as an important means to deposit different cell types and biomaterials in heterogeneous structures that morphologically and structurally mimic complex biological tissue architectures.

Now, a new Scientific Reports study from the laboratories of Claudia Bearzi and Roberto Rizzi (IBCN, CNR, Rome, Italy) has employed a high-resolution microfluidic printing head (MPH)-based approach to generate vascularized cardiac tissue from induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and human umbilical vein endothelial cells (HUVECs) [1]. The authors anticipate that their research will represent a significant step towards the replacement of damaged myocardium [2] in patients suffering from cardiovascular diseases [3, 4] by creating complex cardiac tissue constructs that favor synchronous cardiac contractions and large vessel formation.

Maiullari et al. encapsulated mouse iPSC-CMs and HUVECS in hydrogel strands containing a precisely tuned mix of alginate and PEG monoacrylate-fibrinogen (PF) before printing through the lab’s custom MPH that allows the simultaneous and controlled deposition of multiple cell-laden bioinks in the required precise 3D arrangement. While alginate allows the controlled deposition of hydrogel fibers, PF allows cell spreading and differentiation during long-term in vitro culture. 

Importantly, this precise mode of bioprinting in combination with the blood vessel-like shapes generated by HUVECs permitted the generation of heterogeneous cardiac tissue with the long-range cellular organization of iPSC-derived CMs required for contractile activity. The proper alignment/orientation of iPSC-CMs is essential for synchronous cardiac contractions, and assessments revealed that their engineered cardiac tissue partially resembled functional native cardiac tissue. Furthermore, the authors demonstrated for the first time that the engineered cardiac tissue integrated well into the host’s vasculature during in vivo testing, thereby providing a rapid blood supply to the implant to avoid necrosis.

Not only do the authors highlight MPH-mediated bioprinting of iPSC-CMs and HUVECs as a means to generate host-like vascularized cardiac tissue for innovative reconstructive therapies in the heart, but they also highlight an opportunity to apply bioprinted endothelial cells in the revascularization of ischemic or damaged organs to counteract cell death and promote regeneration.

For more exciting studies on bioprinting and stem cell therapies for cardiovascular disease, stay tuned to the Stem Cells Portal!

References

  1. Maiullari F, Costantini M, Milan M, et al., A multi-cellular 3D bioprinting approach for vascularized heart tissue engineering based on HUVECs and iPSC-derived cardiomyocytes. Scientific Reports 2018;8:13532.
  2. Jessup M and Brozena S, Heart Failure. New England Journal of Medicine 2003;348:2007-2018.
  3. Lopez AD, Mathers CD, Ezzati M, et al., Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 2006;367:1747-57.
  4. Bui AL, Horwich TB, and Fonarow GC, Epidemiology and risk profile of heart failure. Nature Reviews Cardiology 2010;8:30.