Microfluidic bioprinting of tough hydrogel-based vascular conduits for functional blood vessels

Author:

Wang Di12ORCID,Maharjan Sushila1ORCID,Kuang Xiao1ORCID,Wang Zixuan1,Mille Luis S.1ORCID,Tao Ming3,Yu Peng3,Cao Xia1ORCID,Lian Liming1ORCID,Lv Li1,He Jacqueline Jialu1,Tang Guosheng1,Yuk Hyunwoo4ORCID,Ozaki C. Keith3ORCID,Zhao Xuanhe45ORCID,Zhang Yu Shrike1ORCID

Affiliation:

1. Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, USA.

2. Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100144, P. R. China.

3. Department of Surgery and the Heart and Vascular Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

4. Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

5. Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Abstract

Three-dimensional (3D) bioprinting of vascular tissues that are mechanically and functionally comparable to their native counterparts is an unmet challenge. Here, we developed a tough double-network hydrogel (bio)ink for microfluidic (bio)printing of mono- and dual-layered hollow conduits to recreate vein- and artery-like tissues, respectively. The tough hydrogel consisted of energy-dissipative ionically cross-linked alginate and elastic enzyme–cross-linked gelatin. The 3D bioprinted venous and arterial conduits exhibited key functionalities of respective vessels including relevant mechanical properties, perfusability, barrier performance, expressions of specific markers, and susceptibility to severe acute respiratory syndrome coronavirus 2 pseudo-viral infection. Notably, the arterial conduits revealed physiological vasoconstriction and vasodilatation responses. We further explored the feasibility of these conduits for vascular anastomosis. Together, our study presents biofabrication of mechanically and functionally relevant vascular conduits, showcasing their potentials as vascular models for disease studies in vitro and as grafts for vascular surgeries in vivo, possibly serving broad biomedical applications in the future.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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