Direct 3D printed biocompatible microfluidics: assessment of human mesenchymal stem cell differentiation and cytotoxic drug screening in a dynamic culture system

Abstract

Background In vivo-mimicking conditions are critical in in vitro cell analysis to obtain clinically relevant results. The required conditions, comparable to those prevalent in nature, can be provided by microfluidic dynamic cell cultures. Microfluidics can be used to fabricate and test the functionality and biocompatibility of newly developed nanosystems or to apply micro- and nanoelectromechanical systems embedded in a microfluidic system. However, the use of microfluidic systems is often hampered by their accessibility, acquisition cost, or customization, especially for scientists whose primary research focus is not microfluidics. Results Here we present a method for 3D printing that can be applied without special prior knowledge and sophisticated equipment to produce various ready-to-use microfluidic components with a size of 100 µm. Compared to other available methods, 3D printing using fused deposition modeling (FDM) offers several advantages, such as time-reduction and avoidance of sophisticated equipment (e.g., photolithography), as well as excellent biocompatibility and avoidance of toxic, leaching chemicals or post-processing (e.g., stereolithography). We further demonstrate the ease of use of the method for two relevant applications: a cytotoxicity screening system and an osteoblastic differentiation assay. To our knowledge, this is the first time an application including treatment, long-term cell culture and analysis on one chip has been demonstrated in a directly 3D-printed microfluidic chip. Conclusion The direct 3D printing method is tested and validated for various microfluidic components that can be combined on a chip depending on the specific requirements of the experiment. The ease of use and production opens up the potential of microfluidics to a wide range of users, especially in biomedical research. Our demonstration of its use as a cytotoxicity screening system and as an assay for osteoblastic differentiation shows the methods potential in the development of novel biomedical applications. With the presented method, we aim to disseminate microfluidics as a standard method in biomedical research, thus improving the reproducibility and transferability of results to clinical applications. Graphical Abstract

Rapid Phenotypic Antibiotics Susceptibility Analysis by a 3D Printed Prototype

“…Device Fabrication: Prototype devices were fabricated as previously described. [42] Briefly, a CAD model was created in Autodesk Fusion 360 (Autodesk, United States) and processed in the slicer software Ulti- maker Cura (Version 4.6.1, Ultimaker, Netherlands). Prototype devices were printed with an Ultimaker 3 (Ultimaker, Netherlands) FDM 3D printer with a 0.4 mm nozzle head using the polymer PMMA-transparent (PMM300XCLR) purchased from filamentworld.com (Germany).…”

Microfluidics in High-Throughput Drug Screening: Organ-on-a-Chip and C. elegans-Based Innovations

“…In addition to these two materials, the recent rise of 3D printing has led to the emergence of 3D-printed biochips using a variety of non-toxic resins [62].…”

Advancements in tissue engineering for articular cartilage regeneration

“…Solid stress allows the study of changes in cell morphology and behavior induced by external static or dynamic compression [ 211 ]. Microfluidics provides a useful tool for simulating the in vivo microenvironment in a microarray culture system and controlling the application of compressive forces to individual cells in both 2D and 3D culture models [ 209 , 212 ]( Fig. 3 ).…”