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International Journal of Bioprinting                              Rheology-informed machine learning model




            cases, including new printing parameters with trained   and highly time-consuming [55-57] . Therefore, it is crucial
            bioink materials, new concentrations of the trained bioink   to develop an efficient machine learning model that
            constituents, and untrained bioink compositions with the   is suitable for small dataset sizes while ensuring high
            new  material.  For  different  nozzle  velocities,  the  results   prediction accuracy. With the hierarchical architecture of
            of  the  study  showed  that  the  RIHML  model  exhibited   the developed model, RIHML can effectively predict the
            the lowest error percentage (around 18%) in predicting   printing resolution of extrusion-based bioprinting using
            the printing resolution. Additionally, the RIHML model   small datasets. In this study, the dataset of 537 numbers
            showed low error (around 10%) in predicting the printing   of bioink rheological properties and printing process was
            resolution for different pressures, which is 2-fold and   used for training, validation, and testing of the machine
            5-fold lower than CDML and PDML, respectively.     learning model. Several bioprinting studies employed
            Moreover, the printing resolution for different bioink   small datasets to optimize printing resolution and
            concentrations was predicted, and it was demonstrated   parameters using conventional machine learning skills,
            that the RIHML model exhibited lower error percentages   but their practical applications were limited due to low
            than the CDML model for all the different concentrations   prediction accuracy, poor expandability, and low training
            of bioink constituents such as F127, gelatin, xanthan gum,   efficiency [41,42,44,45] . However, the RIHML model can easily
            and CaCl . Additionally, the machine learning models   generalize and embrace new data, even with a small dataset
                    2
            were used to predict the printing resolution with a new   size owing to its intrinsic features in the dataset that are not
            material (CNC) added to the alginate-based bioink, which   biased to specific bioink, but rather are general. Moreover,
            is the most challenging among the three cases. The results   due to the potential of data accumulation, if various
            of the study showed that RIHML can predict the printing   rheological and printing data are additionally collected
            resolution with reasonably low errors while the printing   in sufficient size for deep learning, prediction using a
            resolution was hardly predictable using CDML with   rheology-informed neural network with deeper hidden
            considerably large errors.                         layers may be attempted.

               Overall, the experimental results indicate that the   Although the RIHML model has the potential for
            rheology-informed hierarchical model can be a useful   accurate and robust prediction of printability, there is still
            tool to predict the printing resolution of extrusion-based   room for improvement. Due to the generalizability of the
            bioprinting. Furthermore, while other studies related   bioink properties, a wider range of rheological properties
            to  the  prediction  of  printability  in  bioprinting  could   of bioinks can enhance the prediction accuracy of the
            anticipate the printability changes only with limited   RIHML model. For instance, in the results presented in
            parameters, such as bioink material properties or printing   Figure 7C, relatively high errors were observed in F127
            conditions, the RIHML model is versatile to predict the   with a concentration of 45%. Specifically, this may occur
            printing resolution in different conditions of varying   because its viscosity and storage modulus were the highest
            printing parameters, varying material concentrations,   around the upper bound of the rheological data range.
            and new bioink compositions [40,43,54] . Additionally,   In terms of future work, it would be beneficial to further
            the  neural  network  structure  of RIHML is  based  on   validate the performance of the RIHML model from other
            rheological properties, which can be widely obtained   types of bioprinting methods, such as inkjet-based or
            from most biomaterials, and it can be trained without   laser-assisted bioprinting, to demonstrate the feasibility of
            significant alterations of the structure. Therefore, the   rheology-based prediction of printability across different
            RIHML model is adaptable and expandable compared to   bioprinting methods. Additionally, future studies could
            the conventional models, and the printing and rheological   investigate the potential of the RIHML model in predicting
            datasets may be accumulated to enhance the prediction    other aspects of printability, such as the extrudability,
            accuracy.                                          pore size, pore shape, and shape fidelity of the stacked
                                                               layers.
               Since  the  formulation  of  bioinks  and  the  process  of
            bioprinting are  more  complicated  and correlated,  the   5. Conclusion
            prediction of printability in 3D bioprinting has become
            more challenging. Recently, there have been attempts   In conclusion, this study suggests that the rheology-
            related to the prediction of bioprinting printability using   informed hierarchical model can be a useful tool for
            machine  learning.  However,  unlike  other  fields  such  as   predicting the printing resolution of constructs fabricated
            medical imaging and genetics, 3D bioprinting suffers   by  extrusion-based  bioprinting.  Interestingly,  the  RIHML
            from  data  size,  which  may  hardly  be  large  because  the   model demonstrated the lowest errors (around 18%) in
            preparation of bioinks with various compositions and   predicting the printing resolution for different printing
            their 3D printing with multiple parameters are sequential   parameters such as nozzle velocities and pressures,

            Volume 9 Issue 6 (2023)                        320                          https://doi.org/10.36922/ijb.1280
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