Biomaterials. 2016 Dec;110:45-59. doi: 10.1016/j.biomaterials.2016.09.003. Epub 2016 Sep 5.

Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip.

Zhang YS¹, Arneri A², Bersini S³, Shin SR⁴, Zhu K⁵, Goli-Malekabadi Z⁶, Aleman J⁷, Colosi C⁸, Busignani F⁹, Dell'Erba V¹⁰, Bishop C¹¹, Shupe T¹¹, Demarchi D¹², Moretti M¹³, Rasponi M¹⁴, Dokmeci MR⁴, Atala A¹¹, Khademhosseini A¹⁵.

Abstract

Engineering cardiac tissues and organ models remains a great challenge due to the hierarchical structure of the native myocardium. The need of integrating blood vessels brings additional complexity, limiting the available approaches that are suitable to produce integrated cardiovascular organoids. In this work we propose a novel hybrid strategy based on 3D bioprinting, to fabricate endothelialized myocardium. Enabled by the use of our composite bioink, endothelial cells directly bioprinted within microfibrous hydrogel scaffolds gradually migrated towards the peripheries of the microfibers to form a layer of confluent endothelium. Together with controlled anisotropy, this 3D endothelial bed was then seeded with cardiomyocytes to generate aligned myocardium capable of spontaneous and synchronous contraction. We further embedded the organoids into a specially designed microfluidic perfusion bioreactor to complete the endothelialized-myocardium-on-a-chip platform for cardiovascular toxicity evaluation. Finally, we demonstrated that such a technique could be translated to human cardiomyocytes derived from induced pluripotent stem cells to construct endothelialized human myocardium. We believe that our method for generation of endothelialized organoids fabricated through an innovative 3D bioprinting technology may find widespread applications in regenerative medicine, drug screening, and potentially disease modeling.