Cell viability prediction and optimization in extrusion-based bioprinting via neural network-based Bayesian optimization models.

The fields of regenerative medicine and cancer modeling have witnessed tremendous growth in the application of 3D bioprinting. Maintaining high cell viability throughout the bioprinting process is crucial for the success of this technology, as it directly affects the accuracy of the 3D bioprinted models, the validity of experimental results, and the discovery of new therapeutic approaches. Therefore, optimizing bioprinting conditions, which include numerous variables influencing cell viability during and after the procedure, is of utmost importance to achieve desirable results. So far, these optimizations have been accomplished primarily through trial and error and repeating multiple time-consuming and costly experiments. To address this challenge, we initiated the process by creating a dataset of these parameters for gelatin and alginate-based bioinks and the corresponding cell viability by integrating data obtained in our laboratory and those derived from the literature. Then, we developed machine learning models to predict cell viability based on different bioprinting variables. The trained neural network yielded regression R^2 value of 0.71 and classification accuracy of 0.86. Compared to models that have been developed so far, the performance of our models is superior and shows great prediction results. The study further introduces a novel optimization strategy that employs the Bayesian optimization model in combination with the developed regression neural network to determine the optimal combination of the selected bioprinting parameters to maximize cell viability and eliminate trial-and-error experiments. Finally, we experimentally validated the optimization model's performance.

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