Combination of Extrusion and Drop-on-Demand Bioprinting in One Process Enables the Local Placement of Cells or Signaling Factors Into (Bio) Printed Hydrogel Structures

Sep 28, 2026

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Combining volumetric hydrogel fabrication via extrusion bioprinting with the high-precision drop-on-demand (DoD) technique expands biofabrication capabilities. This technical report presents a method where a solenoid micro-pipette is integrated into an extrusion (bio)printing system to dispense small volumes of bioinks into extrusion-printed hydrogel constructs. Three examples demonstrate patterned cell or growth-factor placement in 3D constructs, shaping developmental processes. Human cells in low-viscosity bioinks stayed viable and functional for up to 28 days, and local VEGF signaling recruited endothelial cells and fibroblasts into previously cell-free areas, supporting complex multi-component tissue models.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Introduction

Rationale for combining extrusion and DoD bioprinting

Integrated DoD micro-pipette system concept

Application examples and outcomes

Engineering in Life Sciences TECHNICAL REPORT Combination of Extrusion and Drop-on-Demand Bioprinting in One Process Enables the Local Placement of Cells or Signaling Factors Into (Bio) Printed Hydrogel Structures Finn Dani1 Nieves Cubo-Matteo2 Leonie Schlicht1 Michael Gelinsky1 Anja Lode1 1 Centre for Translational Bone, Joint and Soft Tissue Research, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany 2 Grupo de Investigación ARIES, Universidad Nebrija, Madrid, Spain Correspondence: Anja Lode (anja.lode@tu-dresden.de) Received: 1 August 2025 Revised: 14 November 2025 Accepted: 8 December 2025 Keywords: bioprinting | cell migration | cell placement | drop-on-demand | organoid ABSTRACT Combining the volumetric fabrication of hydrogel constructs using extrusion bioprinting with highly precise drop-on-demand (DoD) bioprinting offers exciting opportunities in biofabrication. This technical report presents a technique in which a solenoid micro-pipette is operated as an additional tool in an extrusion (bio)printing system to deposit small volumes of bioinks into extrusion-printed hydrogel constructs. Using three exemplary approaches, we show that this enables the patterned placement of cells or growth factors within 3D constructs and thus influences developmental processes. Human cells within low-viscosity bioinks, deposited into extrusion-printed hydrogel constructs by filling inter-strand cavities or by injection into the hydrogel strands, maintained their viability and functionality up to 28 days. As demonstrated for salivary gland cells, the properties of the hydrogel matrix can influence the fate of the injected cells: In a stiff alginate (Alg)-based hydrogel, they formed aggregates, which is beneficial for organoid formation, and in softer hydrogels, they migrated to neighboring cell clusters. Locally injected signaling factors such as vascular endothelial growth factor (VEGF) attracted endothelial cells and fibroblasts, which migrated into previously cell-free hydrogel areas. The combination of extrusion and DoD bioprinting opens new approaches to integrate different cell types and functionalizations in one construct, facilitating the creation of more complex and dynamic models. 1 Introduction Extrusion-based 3D bioprinting, the strand-wise deposition of cell-loaded hydrogels, and drop-on-demand (DoD) bioprinting, the placement of cell-loaded droplets, are commonly used and well-established techniques in biofabrication. Each of them offers distinct advantages: Extrusion bioprinting excels at depositing high-viscosity bioinks with high shape fidelity to construct robust and volumetric cell-loaded constructs of clinically relevant size [1, 2] . DoD bioprinting allows for the precise dispensing of lowviscosity bioinks with volumes in the nanoliter range and even of single cells [3] . The combination of both techniques would make it possible to unite volumetric 3D bioprinting with high-precision placement of biological components, such as cells or signaling factors, to expand the possibilities for reproducing the complex architecture of native tissues. However, up to now, there are only a few studies which applied both techniques in one fabrication process of complex tissue models: A human skin model was | Abbreviations: Alg, alginate; C, collagen type I; cLSM, confocal laser scanning microscopy; DMEM, Dulbecco’s modified Eagle’s medium; DoD, drop-on-demand; F, fibrinogen; FBS, fetal bovine serum; HCM, hypoxia-conditioned medium; hMSGC, human minor salivary gland cells; HUVEC, human umbilical vein endothelial cells; MC, methylcellulose; NHDF, normal human dermal fibroblasts; PBS, phosphate-buffered saline; VEGF, vascular endothelial growth factor .
| | --- | | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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FAQs

How does the solenoid micro-pipette integrate with extrusion bioprinting in this process?

The micro-pipette acts as an additional tool in the extrusion (bio)printing system, collecting (bio)inks from a reservoir and depositing small volumes onto a surface or into an extrusion-printed hydrogel construct.

What was demonstrated about cell viability and function after deposition?

Human cells within low-viscosity bioinks deposited into extrusion-printed hydrogel constructs maintained viability and functionality for up to 28 days.

How do hydrogel properties affect injected cells and organoid-related behavior?

In a stiff alginate-based hydrogel, injected cells formed aggregates favorable for organoid formation, while in softer hydrogels they migrated toward neighboring cell clusters.

Sep 28, 2026

Uploaded by Đào