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Bioprinting 3D Microfibrous Scaffolds for Engineering Endothelialized Myocardium and Heart-on-a-Chip
accepted manuscript... using Organovo MMX
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.
Direct 3D Bioprinting of Perfusable Vascular Constructs Using a Blend Bioink
Weitao Jiaa, b, c, 1, P. Selcan Gungor-Ozkerima, b, 1, Yu Shrike Zhanga, b, d, , 1, , Kan Yuea, b, Kai Zhua, b, e, Wanjun Liua, b, Qingment Pia, b, Batzaya Byambaaa, b, Mehmet Remzi Dokmecia, b, d, Su Ryon Shina, b, d, , , Ali Khademhosseinia, b, d, f, g, ,
a Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, USA
b Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
c Department of Orthopedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, P.R. China
d Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA
e Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai 200032, PR China
f Department of Bioindustrial Technologies, College of Animal Bioscience and Technology, Konkuk University, Seoul 143-701, Republic of Korea
g Department of Physics, King Abdulaziz University, Jeddah 21569, Saudi Arabia
Received 6 February 2016, Revised 23 July 2016, Accepted 31 July 2016, Available online 2 August 2016