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International Journal of Bioprinting                              ML-generated GelMA compression database






























                Figure 1. The input and output variables of the system to be optimized. Abbreviations: GelMA: Gelatin methacryloyl; UV: Ultraviolet light.



            Section 2.5). Four replicates of each experimental condition   (i) select experimental settings at which scaffolds should
            were printed to improve reliability. Printed scaffolds were   be photo-crosslinked and tested, and (ii) use these results
            placed in Petri dishes, immersed in cell culture medium,   to update the GP model in the system. The process can be
            and incubated overnight at 37°C.                   understood as follows:
            2.4. Compression testing                             (i)  Initialization: Random experimental settings (a
            The scaffolds were subjected to mechanical stress testing   random set at each of the three GelMA concentrations)
            using a uniaxial EZ-L testing machine (Shimadzu, Japan)   are chosen, and testing of the scaffolds is conducted.
            (Figure 2). This equipment allows for the calculation of   The resulting compression modulus was then pre-
            stress and stiffness of the material, which can be used for   processed, where the experimental settings (X
            theoretical calculations of pressure. A 10 N kit was used for   variables) are scaled (to a range of 0–1), and the
            the testing in this experiment. After overnight incubation   compression modulus values (Y) are standardized
            in the cell culture medium, each GelMA scaffold was     (to have a mean of 0 and standard deviation of 1).
            removed and placed on the testing platform. The thickness    (ii)  GP model fitting: The pre-processed data from (i) are
            of the scaffold was approximately 1.5 mm. The compression   used to fit the GP model. Once fitted, the maximum
            interval was set to 1 mm, achieving 67% strain, with the   uncertainty of the system is checked against the
            corresponding pressure at 30–50% strain selected for    “uncertainty threshold.” If found to be within the
            calculating the compression modulus (Figure 2).         uncertainty threshold, experimentation is halted.
                                                                    Otherwise, the process continues with (iii).
            2.5. Bayesian optimization framework
            The algorithm used in this study was a BO-based    (iii)  Acquisition function optimization: The predicted
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            framework  with GP as the probabilistic model.  We      standard deviation of the GP model was utilized as
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            used BO to guide the sampling of experimental settings,   the acquisition function, and a batch of experiments
            improving the accuracy of the GP model in predicting    was sampled for the next iteration. Following each
            scaffold strength, as indicated by the compression modulus   sample added to the batch, the GP is updated
            value. Within the BO framework, an acquisition function   temporarily and only partially (i.e., only predictive
            tailored toward uncertainty reduction recommended       variance computation is updated) to determine
            experimental settings for the system. This is automatically   the experiments suitable for this batch. This
            performed  by  the  framework  using  the  variable  search   process continues until the batch number is filled
            space to assess previous experiments, thereby improving   up. Additionally, this batch selection process is
            the system based on the key findings. Figure 3 illustrates the   constrained, such that all settings in the batch have
            machine learning search algorithm used to concurrently   the same GelMA concentration.


            Volume 10 Issue 5 (2024)                       562                                doi: 10.36922/ijb.3814
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