Magnetic resonance imaging as a tool for quality control in extrusion‐based bioprinting

Abstract

Bioprinting is gaining importance for the manufacturing of tailor‐made hydrogel scaffolds in tissue engineering, pharmaceutical research and cell therapy. However, structure fidelity and geometric deviations of printed objects heavily influence mass transport and process reproducibility. Fast, three‐dimensional and nondestructive quality control methods will be decisive for the approval in larger studies or industry. Magnetic resonance imaging (MRI) meets these requirements for characterizing heterogeneous soft materials with different properties. Complementary to the idea of decentralized 3D printing, magnetic resonance tomography is common in medicine, and image data processing tools can be transferred system‐independently. In this study, a MRI measurement and image analysis protocol was evaluated to jointly assess the reproducibility of three different hydrogels and a reference material. Critical parameters for object quality, namely porosity, hole areas and deviations along the height of the scaffolds are discussed. Geometric deviations could be correlated to specific process parameters, anomalies of the ink or changes of ambient conditions. This strategy allows the systematic investigation of complex 3D objects as well as an implementation as a process control tool. Combined with the monitoring of metadata this approach might pave the way for future industrial applications of 3D printing in the field of biopharmaceutics.

Virtual Reality as Tool for Bioprinting Quality Inspection: A Proof of Principle

“…MRI as a non-destructive analytical method in the field of bioprinting was discussed in a previous study ( Schmieg et al, 2022 ), highlighting the importance to ensure quality and reproducibility when aiming towards industrial or clinical applications. While the previous work was focusing on analytical method development and the calculation of parameters describing the reproducibility of the bioprinting process, this study’s focus is on the development of a workflow for visualizing and communicating the complex 3D data.…”

“…To localize cells within opaque 3D objects, the method used in the previous study ( Schmieg et al, 2022 ) was adapted towards cell tracking. Using MRI in combination with magnetic particle-tags is commonly used for cell tracking purposes ( Billotey et al, 2003 ; Tallheden et al, 2006 ; Bulte, 2009 ).…”

“…In short, meandering strands were extruded to form a cubic scaffold with dimensions of 8.8 mm × 8.8 mm × 8 mm (5 strands with a distance of 2.2 mm, layer height 0.20 mm) with a pressure of 20 kPa and a velocity of 20 mm/s at 23°C. Directly after the printing, the objects were crosslinked with CaCl 2 -solution (Cellink AB) for 20 min ( Schmieg et al, 2022 ) and stored at room temperature in a 10 ml vial for a maximum of 2.5 h with closed lid before MRI measurement. Three objects could be 3D printed with 3.3 ml of bioink starting material (n scaffolds_per_cartridge = 3).…”

“…The cubic scaffolds were imaged with an Avance HD III SWB 200 MHz tomograph (Bruker BioSpin GmbH, Ettlingen, Germany) equipped with a 20 mm birdcage (MICWB40, Bruker) with air as background medium at 20°C as described in ( Schmieg et al, 2022 ). With pulse sequence rapid acquisition with relaxation enhancement (RARE) ( Callaghan, 1991 ; Kimmich, 1997 ; Bernstein et al, 2004 ), a stack of 15 axial slices was measured, which resulted in a measurement time of 26 min.…”

“…In the present study, a workflow for visualization of the cell distribution within bioprinted samples in VR was developed and evaluated. The development includes the extension of the previously developed MRI method ( Schmieg et al, 2022 ) toward the detection of cells using magnetic tags and the transfer of the generated MRI data to a VR environment. In a first case study, quality inspection of the critical quality attribute (cQA) cell distribution using VR was done.…”