Dataset Information

Machine Assisted Experimentation of Extrusion-Based Bioprinting Systems.

ABSTRACT: Optimization of extrusion-based bioprinting (EBB) parameters have been systematically conducted through experimentation. However, the process is time- and resource-intensive and not easily translatable to other laboratories. This study approaches EBB parameter optimization through machine learning (ML) models trained using data collected from the published literature. We investigated regression-based and classification-based ML models and their abilities to predict printing outcomes of cell viability and filament diameter for cell-containing alginate and gelatin composite bioinks. In addition, we interrogated if regression-based models can predict suitable extrusion pressure given the desired cell viability when keeping other experimental parameters constant. We also compared models trained across data from general literature to models trained across data from one literature source that utilized alginate and gelatin bioinks. The results indicate that models trained on large amounts of data can impart physical trends on cell viability, filament diameter, and extrusion pressure seen in past literature. Regression models trained on the larger dataset also predict cell viability closer to experimental values for material concentration combinations not seen in training data of the single-paper-based regression models. While the best performing classification models for cell viability can achieve an average prediction accuracy of 70%, the cell viability predictions remained constant despite altering input parameter combinations. Our trained models on bioprinting literature data show the potential usage of applying ML models to bioprinting experimental design.

SUBMITTER: Tian S

PROVIDER: S-EPMC8305959 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Extrusion-based bioprinting (EBB) represents one of the most used deposition technologies in the field of bioprinting, thanks to key advantages such as the easy-to-use hardware and the wide variety of materials that can be successfully printed. In recent years, research efforts have been focused on implementing a quality control loop for EBB, which can reduce the trial-and-error process necessary to optimize the printing parameters for a specific ink, standardize the results of a print across multiple laboratories, and so accelerate the translation of extrusion bioprinted products to more impactful clinical applications. Due to its capacity to acquire relevant features from a training dataset and generalize to unseen data, machine learning (ML) is currently being studied in literature as a relevant enabling technology for quality control in EBB. In this context, we propose a robust, deep learning-based control loop to automatically optimize the printing parameters and monitor the printing process online. We collected a comprehensive dataset of EBB prints by recording the process with a high-resolution webcam. To model multiple printing scenarios, each video represents a combination of multiple parameters, including printing set-up (either mechanical or pneumatic extrusion), material color, layer height, and infill density. After pre-processing, the collected dataset was used to thoroughly train and evaluate an ad hoc defined convolutional neural network by controlling over-fitting and optimizing the prediction time of the network. Finally, the ML model was used in a control loop to: (i) monitor the printing process and detect if a print with an error could be stopped before completion to save material and time and (ii) automatically optimize the printing parameters by combining the ML model with a previously published mathematical model of the EBB process. Altogether, we demonstrated for the first time how ML techniques can be used to automatize the EBB process, paving the way for a total quality control loop of the printing process.

Project description:Extrusion-based 3D bioprinting enables the production of customized hydrogel structures that can be employed in flow reactors when printing with enzyme-containing inks. The present study compares inks based on either low-melt agarose or agar at different concentrations (3-6%) and loaded with the thermostable enzyme esterase 2 from the thermophilic organism Alicyclobacillus acidocaldarius (AaEst2) with regard to their suitability for the fabrication of such enzymatically active hydrogels. A customized printer setup including a heatable nozzle and a cooled substrate was established to allow for clean and reproducible prints. The inks and printed hydrogel samples were characterized using rheological measurements and compression tests. All inks were found to be sufficiently printable to create lattices without overhangs, but printing quality was strongly enhanced at 4.5% polymer or more. The produced hydrogels were characterized regarding mechanical strength and diffusibility. For both properties, a strong correlation with polymer concentration was observed with highly concentrated hydrogels being more stable and less diffusible. Agar hydrogels were found to be more stable and show higher diffusion rates than comparable agarose hydrogels. Enzyme leaching was identified as a major drawback of agar hydrogels, while hardly any leaching from agarose hydrogels was detected. The poor ability of agar hydrogels to permanently immobilize enzymes indicates their limited suitability for their employment in perfused biocatalytic reactors. Batch-based activity assays showed that the enzymatic activity of agar hydrogels was roughly twice as high as the activity of agarose hydrogels which was mostly attributed to the increased amount of enzyme leaching. Agarose bioinks with at least 4.5% polymer were identified as the most suitable of the investigated inks for the printing of biocatalytic reactors with AaEst2. Drawbacks of these inks are limited mechanical and thermal stability, not allowing the operation of a reactor at the optimum temperature of AaEst2 which is above the melting point of the employed low-melt agarose.

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Machine Assisted Experimentation of Extrusion-Based Bioprinting Systems.

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