Microfluidics and 3D Printing for Biomedical Applications

A special issue of Micromachines (ISSN 2072-666X). This special issue belongs to the section "D3: 3D Printing and Additive Manufacturing".

Deadline for manuscript submissions: 28 February 2025 | Viewed by 6743

Special Issue Editors


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Guest Editor
Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN 46556, USA
Interests: tissue engineering; bioprinting; cancer
Special Issues, Collections and Topics in MDPI journals

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Guest Editor Assistant
Department of Surgery, Harvard Medical School, Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, 51 Blossom Street, Boston, MA 02114, USA
Interests: cardiac tissue engineering; hepatic tissue engineering; microfluidics; endothelial cells

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Guest Editor Assistant
Harvard Medical School Wyss Institute, Boston, MA 02215, USA
Interests: cardiac tissue engineering; bioprinting

Special Issue Information

Dear Colleagues,

Microfluidics and 3D printing are two promising microfabrication techniques that have recently gained attention in the biomedical field because of their reliability, precision, and wide range of applications. Microfluidics allows for the fabrication of microscale tissue and disease models that can be used to test drug responses recapitulating human clinical conditions. Three-dimensional printing provides spatial and temporal control on the type, concentration, and distribution of cells, signaling molecules, and materials, enabling the construction of functional tissues and disease models with high precision and complexity. These two techniques make it possible to create a 3D microenvironment for the cells to mimic cell–cell and cell–material interactions in the body, which are essential for tissue-level maturity and functionality.

This Special Issue seeks to showcase research papers and review articles that focus on the tissue engineering applications of microfluidics and 3D printing, including organs-on-chips, tissue engineering scaffolds, disease models, and drug testing platforms.

Dr. Gokhan Bahcecioglu
Guest Editor

Dr. Bradley Ellis
Dr. Gozde Basara
Guest Editor Assistants

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Keywords

  • 3D printing
  • bioprinting
  • microfluidics
  • organs-on-chips
  • functional tissues
  • disease modeling

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Published Papers (5 papers)

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Research

19 pages, 7528 KiB  
Article
Towards a 3D-Printed Millifluidic Device for Investigating Cellular Processes
by Jared A. Engelken, Tobias Butelmann, Fabian Tribukait-Riemenschneider and V. Prasad Shastri
Micromachines 2024, 15(11), 1348; https://doi.org/10.3390/mi15111348 - 31 Oct 2024
Viewed by 677
Abstract
Microfluidic devices (µFDs) have been explored extensively in drug screening and studying cellular processes such as migration and metastasis. However, the fabrication and implementation of microfluidic devices pose cost and logistical challenges that limit wider-spread adoption. Despite these challenges, light-based 3D printing offers [...] Read more.
Microfluidic devices (µFDs) have been explored extensively in drug screening and studying cellular processes such as migration and metastasis. However, the fabrication and implementation of microfluidic devices pose cost and logistical challenges that limit wider-spread adoption. Despite these challenges, light-based 3D printing offers a potential alternative to device fabrication. This study reports on the development of millifluidic devices (MiFDs) for disease modeling and elucidates the methods and implications of the design, production, and testing of 3D-printed MiFDs. It further details how such millifluidic devices can be cost-efficiently and effortlessly produced. The MiFD was developed through an iterative process with analytical tests (flow tests, leak tests, cytotoxicity assays, and microscopic analyses), driving design evolution and determination of the suitability of the devices for disease modeling and cancer research. The design evolution also considered flow within tissues and replicates interstitial flow between the main flow path and the modules designed to house and support organ-mimicking cancer cell spheroids. Although the primary stereolithographic (SLA) resin used in this study showed cytotoxic potential despite its biocompatibility certifications, the MiFDs possessed essential attributes for cell culturing. In summary, SLA 3D printing enables the production of MiFDs as a cost-effective, rapid prototyping alternative to standard µFD fabrication for investigating disease-related processes. Full article
(This article belongs to the Special Issue Microfluidics and 3D Printing for Biomedical Applications)
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23 pages, 10697 KiB  
Article
Mechanical Property of Thermoplastic Polyurethane Vascular Stents Fabricated by Fused Filament Fabrication
by Yun Zhai, Zezhi Sun, Tie Zhang, Changchun Zhou and Xiangpeng Kong
Micromachines 2024, 15(10), 1266; https://doi.org/10.3390/mi15101266 - 17 Oct 2024
Viewed by 756
Abstract
Vascular stents have many applications in treating arterial stenosis and other vascular-related diseases. The ideal vascular stent for clinical application should have radial support and axial bending mechanical properties that meet the requirements of vascular deformation coordination. The materials used for vascular stents [...] Read more.
Vascular stents have many applications in treating arterial stenosis and other vascular-related diseases. The ideal vascular stent for clinical application should have radial support and axial bending mechanical properties that meet the requirements of vascular deformation coordination. The materials used for vascular stents implanted in the human body should have corresponding biocompatibility to ensure that the stents do not cause coagulation, hemolysis, and other reactions in the blood. This study fabricated four types of vascular stents, including inner hexagon, arrowhead, quadrilateral, and outer hexagonal, using fused filament fabrication technology and thermoplastic polyurethane (TPU) as materials. By evaluating the effects of edge width and wall thickness on the radial support and axial bending performance, it was found that the inner hexagonal stent exhibited the best radial support and axial bending performance under the same conditions. The design and fabrication of vascular stents based on 3D printing technology have promising application prospects in personalized customized vascular repair therapy. Full article
(This article belongs to the Special Issue Microfluidics and 3D Printing for Biomedical Applications)
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14 pages, 3841 KiB  
Article
Synthesis of Submicron CaCO3 Particles in 3D-Printed Microfluidic Chips Supporting Advection and Diffusion Mixing
by Ivan Reznik, Ekaterina Kolesova, Anna Pestereva, Konstantin Baranov, Yury Osin, Kirill Bogdanov, Jacobus Swart, Stanislav Moshkalev and Anna Orlova
Micromachines 2024, 15(5), 652; https://doi.org/10.3390/mi15050652 - 15 May 2024
Viewed by 1326
Abstract
Microfluidic technology provides a solution to the challenge of continuous CaCO3 particle synthesis. In this study, we utilized a 3D-printed microfluidic chip to synthesize CaCO3 micro- and nanoparticles in vaterite form. Our primary focus was on investigating a continuous one-phase synthesis [...] Read more.
Microfluidic technology provides a solution to the challenge of continuous CaCO3 particle synthesis. In this study, we utilized a 3D-printed microfluidic chip to synthesize CaCO3 micro- and nanoparticles in vaterite form. Our primary focus was on investigating a continuous one-phase synthesis method tailored for the crystallization of these particles. By employing a combination of confocal and scanning electron microscopy, along with Raman spectroscopy, we were able to thoroughly evaluate the synthesis efficiency. This evaluation included aspects such as particle size distribution, morphology, and polymorph composition. The results unveiled the existence of two distinct synthesis regimes within the 3D-printed microfluidic chips, which featured a channel cross-section of 2 mm2. In the first regime, which was characterized by chaotic advection, particles with an average diameter of around 2 μm were produced, thereby displaying a broad size distribution. Conversely, the second regime, marked by diffusion mixing, led to the synthesis of submicron particles (approximately 800–900 nm in diameter) and even nanosized particles (70–80 nm). This research significantly contributes valuable insights to both the understanding and optimization of microfluidic synthesis processes, particularly in achieving the controlled production of submicron and nanoscale particles. Full article
(This article belongs to the Special Issue Microfluidics and 3D Printing for Biomedical Applications)
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15 pages, 3584 KiB  
Article
Mechanical Characterization of the Erythrocyte Membrane Using a Capacitor-Based Technique
by Doriana Dorta, Carlos Plazaola, Jafeth Carrasco, Maria F. Alves-Rosa, Lorena M. Coronado, Ricardo Correa, Maytee Zambrano, Braulio Gutiérrez-Medina, Erick Sarmiento-Gómez, Carmenza Spadafora and Guadalupe Gonzalez
Micromachines 2024, 15(5), 590; https://doi.org/10.3390/mi15050590 - 28 Apr 2024
Viewed by 1404
Abstract
Pathological processes often change the mechanical properties of cells. Increased rigidity could be a marker of cellular malfunction. Erythrocytes are a type of cell that deforms to squeeze through tiny capillaries; changes in their rigidity can dramatically affect their functionality. Furthermore, differences in [...] Read more.
Pathological processes often change the mechanical properties of cells. Increased rigidity could be a marker of cellular malfunction. Erythrocytes are a type of cell that deforms to squeeze through tiny capillaries; changes in their rigidity can dramatically affect their functionality. Furthermore, differences in the homeostatic elasticity of the cell can be used as a tool for diagnosis and even for choosing the adequate treatment for some illnesses. More accurate types of equipment needed to study biomechanical phenomena at the single-cell level are very costly and thus out of reach for many laboratories around the world. This study presents a simple and low-cost technique to study the rigidity of red blood cells (RBCs) through the application of electric fields in a hand-made microfluidic chamber that uses a capacitor principle. As RBCs are deformed with the application of voltage, cells are observed under a light microscope. From mechanical force vs. deformation data, the elastic constant of the cells is determined. The results obtained with the capacitor-based method were compared with those obtained using optical tweezers, finding good agreement. In addition, P. falciparum-infected erythrocytes were tested with the electric field applicator. Our technique provides a simple means of testing the mechanical properties of individual cells. Full article
(This article belongs to the Special Issue Microfluidics and 3D Printing for Biomedical Applications)
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25 pages, 10664 KiB  
Article
Coaxial 3D Bioprinting Process Research and Performance Tests on Vascular Scaffolds
by Jiarun Sun, Youping Gong, Manli Xu, Huipeng Chen, Huifeng Shao and Rougang Zhou
Micromachines 2024, 15(4), 463; https://doi.org/10.3390/mi15040463 - 29 Mar 2024
Cited by 3 | Viewed by 1921
Abstract
Three-dimensionally printed vascularized tissue, which is suitable for treating human cardiovascular diseases, should possess excellent biocompatibility, mechanical performance, and the structure of complex vascular networks. In this paper, we propose a method for fabricating vascularized tissue based on coaxial 3D bioprinting technology combined [...] Read more.
Three-dimensionally printed vascularized tissue, which is suitable for treating human cardiovascular diseases, should possess excellent biocompatibility, mechanical performance, and the structure of complex vascular networks. In this paper, we propose a method for fabricating vascularized tissue based on coaxial 3D bioprinting technology combined with the mold method. Sodium alginate (SA) solution was chosen as the bioink material, while the cross-linking agent was a calcium chloride (CaCl2) solution. To obtain the optimal parameters for the fabrication of vascular scaffolds, we first formulated theoretical models of a coaxial jet and a vascular network. Subsequently, we conducted a simulation analysis to obtain preliminary process parameters. Based on the aforementioned research, experiments of vascular scaffold fabrication based on the coaxial jet model and experiments of vascular network fabrication were carried out. Finally, we optimized various parameters, such as the flow rate of internal and external solutions, bioink concentration, and cross-linking agent concentration. The performance tests showed that the fabricated vascular scaffolds had levels of satisfactory degradability, water absorption, and mechanical properties that meet the requirements for practical applications. Cellular experiments with stained samples demonstrated satisfactory proliferation of human umbilical vein endothelial cells (HUVECs) within the vascular scaffold over a seven-day period, observed under a fluorescent inverted microscope. The cells showed good biocompatibility with the vascular scaffold. The above results indicate that the fabricated vascular structure initially meet the requirements of vascular scaffolds. Full article
(This article belongs to the Special Issue Microfluidics and 3D Printing for Biomedical Applications)
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