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International

Journal of Bioprinting

RESEARCH ARTICLE
Optimizing nozzle design in extrusion-based

3D bioprinting to minimize mechanical stress
and enhance cell viability

Lorenzo Lombardi 1 id , Annachiara Scalzone * , Chiara Ausilio 1 id ,
2,3 id
Piergiorgio Gentile * , and Daniele Tammaro 1 id
2,4 id
1 Department of Chemical, Materials and Production Engineering, Polytechnic School and Basic
Sciences, University of Naples Federico II, Naples, Campania, Italy
2 School of Engineering, Faculty of Science, Agriculture and Engineering, Newcastle University,
Newcastle upon Tyne, Tyne and Wear, United Kingdom
3
Center for Advanced Biomaterials for Health Care, Italian Institute of Technology, Naples,
Campania, Italy
4 Center for Biomaterials and Tissue Engineering, Polytechnic University of Valencia, Valencia,
Valencia, Spain

Abstract

Extrusion-based three-dimensional bioprinting is a widely used technique for
fabricating cell-laden constructs in tissue engineering and regenerative medicine.
However, the mechanical stresses experienced by cells during the printing process
*Corresponding authors:
Annachiara Scalzone can negatively affect their viability. This study examines the influence of nozzle
(annachiara.scalzone@iit.it) geometry—specifically contraction angle and outlet diameter—on stress distribution
Piergiorgio Gentile and its effects on cell survival. Through a combination of experimental analysis and
(pgentil@upvnet.upv.es) theoretical modeling, the impacts of nozzle design on the balance between shear
Citation: Lombardi L, Scalzone A, and extensional stresses during bioprinting are explored. The findings highlight
Ausilio C, Gentile P, Tammaro D. the importance of optimizing nozzle parameters to minimize mechanical damage
Optimizing nozzle design in and enhance post-printing cell viability. The proposed model provides a framework
extrusion-based 3D bioprinting to
minimize mechanical stress and for guiding nozzle design, offering insights into the development of customized
enhance cell viability. bioprinting strategies that enhance construct fidelity and biological functionality.
Int J Bioprint. 2025;11(4):315-327. These results contribute to advancing bioprinting techniques for applications in
doi: 10.36922/IJB025190182
tissue engineering and regenerative medicine.
Received: May 5, 2025
Revised: June 4, 2025
Accepted: June 16, 2025 Keywords: Customized nozzles; Extensional stress; Extrusion bioprinting
Published online: June 16, 2025
Copyright: © 2025 Author(s).
This is an Open Access article
distributed under the terms of the
Creative Commons Attribution 1. Introduction
License, permitting distribution
and reproduction in any medium, Three-dimensional (3D) printing, also known as additive manufacturing or rapid
provided the original work is prototyping, has been introduced since the late 1980s and provides a new paradigm
properly cited. for engineering design and manufacturing. This technique involves creating objects
Publisher’s Note: AccScience bottom-up by depositing material in a layer-by-layer pattern pre-designed in digital
Publishing remains neutral with files, and, as a result, complex structures can be easily fabricated. Over the past
1
regard to jurisdictional claims in
published maps and institutional decades, additive manufacturing has been widely exploited in tissue engineering,
affiliations. giving rise to a specialized branch known as bioprinting, which integrates 3D printing

Volume 11 Issue 4 (2025) 315 doi: 10.36922/IJB025190182