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

Yu Shrike Zhang, Andrea Arneri, Simone Bersini, Su Ryon Shin, Kai Zhu, Zahra Goli-Malekabadi, Julio Aleman, Cristina Colosi, Fabio Busignani, Valeria Dell'Erba, Colin Bishop, Thomas Shupe, Danilo Demarchi, Matteo Moretti, Marco Rasponi, Mehmet Remzi Dokmeci, Anthony Atala, Ali Khademhosseini

Research output: Contribution to journalArticle

178 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)45-59
Number of pages15
JournalBiomaterials
Volume110
DOIs
Publication statusPublished - Dec 1 2016

Fingerprint

Bioprinting
Hydrogel
Endothelial cells
Blood vessels
Bioreactors
Stem cells
Microfluidics
Hydrogels
Scaffolds
Toxicity
Organoids
Myocardium
Screening
Anisotropy
Tissue
Composite materials
Pharmaceutical Preparations
Cardiac Myocytes
Induced Pluripotent Stem Cells
Preclinical Drug Evaluations

Keywords

  • Bioprinting
  • Cardiac tissue engineering
  • Cardiovascular toxicity
  • Heart-on-a-chip
  • Vascularization

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Zhang, Y. S., Arneri, A., Bersini, S., Shin, S. R., Zhu, K., Goli-Malekabadi, Z., ... Khademhosseini, A. (2016). Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip. Biomaterials, 110, 45-59. https://doi.org/10.1016/j.biomaterials.2016.09.003

Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip. / Zhang, Yu Shrike; Arneri, Andrea; Bersini, Simone; Shin, Su Ryon; Zhu, Kai; Goli-Malekabadi, Zahra; Aleman, Julio; Colosi, Cristina; Busignani, Fabio; Dell'Erba, Valeria; Bishop, Colin; Shupe, Thomas; Demarchi, Danilo; Moretti, Matteo; Rasponi, Marco; Dokmeci, Mehmet Remzi; Atala, Anthony; Khademhosseini, Ali.

In: Biomaterials, Vol. 110, 01.12.2016, p. 45-59.

Research output: Contribution to journalArticle

Zhang, YS, Arneri, A, Bersini, S, Shin, SR, Zhu, K, Goli-Malekabadi, Z, Aleman, J, Colosi, C, Busignani, F, Dell'Erba, V, Bishop, C, Shupe, T, Demarchi, D, Moretti, M, Rasponi, M, Dokmeci, MR, Atala, A & Khademhosseini, A 2016, 'Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip', Biomaterials, vol. 110, pp. 45-59. https://doi.org/10.1016/j.biomaterials.2016.09.003
Zhang, Yu Shrike ; Arneri, Andrea ; Bersini, Simone ; Shin, Su Ryon ; Zhu, Kai ; Goli-Malekabadi, Zahra ; Aleman, Julio ; Colosi, Cristina ; Busignani, Fabio ; Dell'Erba, Valeria ; Bishop, Colin ; Shupe, Thomas ; Demarchi, Danilo ; Moretti, Matteo ; Rasponi, Marco ; Dokmeci, Mehmet Remzi ; Atala, Anthony ; Khademhosseini, Ali. / Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip. In: Biomaterials. 2016 ; Vol. 110. pp. 45-59.
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