Thermo-sensitive Sacrificial Microsphere-based Bioink for Centimeter-scale Tissue with Angiogenesis

¹ Plastic and Reconstructive Surgery Center, Department of Plastic and Reconstructive Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou 310014, Zhejiang, China

² State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou 310027, Zhejiang, China

³ Key Laboratory of Materials Processing and Mold, Zhengzhou University, Zhengzhou 450002, Henan, China

⁴ Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, College of Mechanical Engineering, Zhejiang University, Hangzhou 310027, Zhejiang, China

⁵ Cancer Center, Zhejiang University, Hangzhou 310058, Zhejiang, China

†These authors contributed equally to this work.

IJB 2022, 8(4), 599 https://doi.org/10.18063/ijb.v8i4.599

Received: 24 February 2022 | Accepted: 18 April 2022 | Published online: 4 August 2022

(This article belongs to the Special Issue 3D Bioprinting with Photocurable Bioinks--Call for Papers )

© 2022 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

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Abstract

Centimeter-scale tissue with angiogenesis has become more and more significant in organ regeneration and drug screening. However, traditional bioink has obvious limitations such as balance of nutrient supporting, printability, and vascularization. Here, with “secondary bioprinting” of printed microspheres, an innovative bioink system was proposed, in which the thermo-crosslinked sacrificial gelatin microspheres encapsulating human umbilical vein endothelial cells (HUVECs) printed by electrospraying serve as auxiliary component while gelatin methacryloyl precursor solution mixed with subject cells serve as subject component. Benefiting from the reversible thermo-crosslinking feature, gelatin microspheres would experience solid-liquid conversion during 37°C culturing and form controllable porous nutrient network for promoting the nutrient/oxygen delivery in large-scale tissue and accelerate the functionalization of the encapsulated cells. Meanwhile, the encapsulated HUVECs would be released and attach to the pore boundary, which would further form three-dimensional vessel network inside the tissue with suitable inducing conditions. As an example, vascularized breast tumor tissue over 1 cm was successfully built and the HUVECs showed obvious sprout inside, which indicate the great potential of this bioink system in various biomedical applications.

Keywords

Bioprinting

Angiogenesis

Microsphere

Large-scale tissue

Gelatin methacryloyl

Thermo-sensitive material

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