Dot extrusion bioprinting of spatially controlled heterogenous tumor models

Bioprinting of cell-laden hydrogel constructs providing three-dimensional (3D) spatial pattern capacity and suitable cellular microenvironment have become essential tools in the field of tissue engineering. For heterogeneous tissue development, the printing approaches permitting controllable deposit...

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Main Authors: Xiaoyun Wei, Beisi Huang, Keke Chen, Zicheng Fan, Ling Wang, Mingen Xu
Format: Article
Language:English
Published: Elsevier 2022-11-01
Series:Materials & Design
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0264127522007742
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author Xiaoyun Wei
Beisi Huang
Keke Chen
Zicheng Fan
Ling Wang
Mingen Xu
author_facet Xiaoyun Wei
Beisi Huang
Keke Chen
Zicheng Fan
Ling Wang
Mingen Xu
author_sort Xiaoyun Wei
collection DOAJ
description Bioprinting of cell-laden hydrogel constructs providing three-dimensional (3D) spatial pattern capacity and suitable cellular microenvironment have become essential tools in the field of tissue engineering. For heterogeneous tissue development, the printing approaches permitting controllable deposition of multicellular components in a flexible manner are urgently needed. Here, a facile dot-extrusion printing (DEP) system for one-step generation of cell-laden gelatin methacrylate (GelMa) hydrogel beads (GHBs) is developed, which allows size-tunable GHBs programmable positioned into complex 3D constructs. The GelMa is in situ semi-gelled at the printhead, thus enabling one-step generation of GHBs onto the platform, as a result of improved printing simplicity, fidelity and flexibility. The size and spatial position of the GHBs are adjustable by programming G-code parameters. Further, by integrating multiple printheads, GHBs encapsulating different cellular components can be printed to fabricate heterogeneous tissue constructs, and maintain the post-printed cell viability over 95%. As an example of application, two different tumor-stroma spatial phases were developed through spatial regionally printing tumor cells and normal fibroblasts into juxtapositional or overlapping microcapsule structures, giving an access to study the complex tumor-stroma interactions in different microenvironments. The developed DEP system thus holds promise for creation of complex and heterogeneous tissues toward various biology studies.
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spelling doaj.art-d7a626bb91f4443fb2c1fe4cb0ed52532022-12-22T04:34:22ZengElsevierMaterials & Design0264-12752022-11-01223111152Dot extrusion bioprinting of spatially controlled heterogenous tumor modelsXiaoyun Wei0Beisi Huang1Keke Chen2Zicheng Fan3Ling Wang4Mingen Xu5School of Automation, Hangzhou Dianzi University, Hangzhou 310018, China; Corresponding authors at: School of Automation, Hangzhou Dianzi University, Hangzhou 310018, China (M. Xu).School of Automation, Hangzhou Dianzi University, Hangzhou 310018, ChinaSchool of Automation, Hangzhou Dianzi University, Hangzhou 310018, ChinaSchool of Automation, Hangzhou Dianzi University, Hangzhou 310018, ChinaSchool of Automation, Hangzhou Dianzi University, Hangzhou 310018, China; Key Laboratory of Medical Information and 3D Bioprinting of Zhejiang Province, Hangzhou Dianzi University, Hangzhou 310018, ChinaSchool of Automation, Hangzhou Dianzi University, Hangzhou 310018, China; Key Laboratory of Medical Information and 3D Bioprinting of Zhejiang Province, Hangzhou Dianzi University, Hangzhou 310018, China; Corresponding authors at: School of Automation, Hangzhou Dianzi University, Hangzhou 310018, China (M. Xu).Bioprinting of cell-laden hydrogel constructs providing three-dimensional (3D) spatial pattern capacity and suitable cellular microenvironment have become essential tools in the field of tissue engineering. For heterogeneous tissue development, the printing approaches permitting controllable deposition of multicellular components in a flexible manner are urgently needed. Here, a facile dot-extrusion printing (DEP) system for one-step generation of cell-laden gelatin methacrylate (GelMa) hydrogel beads (GHBs) is developed, which allows size-tunable GHBs programmable positioned into complex 3D constructs. The GelMa is in situ semi-gelled at the printhead, thus enabling one-step generation of GHBs onto the platform, as a result of improved printing simplicity, fidelity and flexibility. The size and spatial position of the GHBs are adjustable by programming G-code parameters. Further, by integrating multiple printheads, GHBs encapsulating different cellular components can be printed to fabricate heterogeneous tissue constructs, and maintain the post-printed cell viability over 95%. As an example of application, two different tumor-stroma spatial phases were developed through spatial regionally printing tumor cells and normal fibroblasts into juxtapositional or overlapping microcapsule structures, giving an access to study the complex tumor-stroma interactions in different microenvironments. The developed DEP system thus holds promise for creation of complex and heterogeneous tissues toward various biology studies.http://www.sciencedirect.com/science/article/pii/S0264127522007742Dot extrusion bioprintingHydrogel beads3D tumor constructsTumor-stroma interactionTumor invasion
spellingShingle Xiaoyun Wei
Beisi Huang
Keke Chen
Zicheng Fan
Ling Wang
Mingen Xu
Dot extrusion bioprinting of spatially controlled heterogenous tumor models
Materials & Design
Dot extrusion bioprinting
Hydrogel beads
3D tumor constructs
Tumor-stroma interaction
Tumor invasion
title Dot extrusion bioprinting of spatially controlled heterogenous tumor models
title_full Dot extrusion bioprinting of spatially controlled heterogenous tumor models
title_fullStr Dot extrusion bioprinting of spatially controlled heterogenous tumor models
title_full_unstemmed Dot extrusion bioprinting of spatially controlled heterogenous tumor models
title_short Dot extrusion bioprinting of spatially controlled heterogenous tumor models
title_sort dot extrusion bioprinting of spatially controlled heterogenous tumor models
topic Dot extrusion bioprinting
Hydrogel beads
3D tumor constructs
Tumor-stroma interaction
Tumor invasion
url http://www.sciencedirect.com/science/article/pii/S0264127522007742
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