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International Journal of Bioprinting                                    Machine learning and 3D bioprinting



            many features can be extracted based on the expert users’   flexibility in discovering hidden patterns and relationships in
            prior knowledge and practical experience. For numerical   complex images. For both methods, the parameters could be
            data, statistical analysis, threshold methods, and frequency   adjusted to improve the classification and regression models.
            analysis are typically used for feature extraction. By contrast,   Labeled/unlabeled datasets, dataset size, and task complexity
            shape, edge, color, and texture detection are widely used   are key factors in ML method selection.
            for image feature extraction. To achieve better predictions,   Researchers worldwide have explored ML applications in
            the informative relevance of these features should be   bioprinting from fundamental perspectives to performance
            carefully chosen for each task . Traditional ML methods,   modeling. The potential adoptions of DL in design and
                                   [20]
            such as Support Vector Machines (SVM) and K-Nearest   fabrication of patient-specific 3D tissue-engineered
            Neighbors, are typically used to build classification or   constructs were reviewed, such as image-processing and
            regression models for such prediction tasks. For example,   segmentation, optimization and in situ correction of printing
            classification models can classify Taylor cone shapes in   parameters and refinement of the tissue maturation process .
                                                                                                            [5]
            EHD bioprinting, identify the reliability of printability,   The authors also reported some relevant practical applications
            and  judge  the  shape  fidelity.  Regression  models  can  be   and summarized that the availability of huge training datasets
            used to optimize the printing parameters and material   and well-defined evaluation metrics are the key factors to
            properties for the desired fiber diameter. One of the most   accelerate the corresponding research areas.
            commonly used ML methods is SVM, and a few powerful
                                                                         [23]
            SVM toolboxes have been launched for prediction models   Shin et al.  discussed the supervised ML, unsupervised
            built  in  MATLAB  or  other  platforms  with  user-friendly   ML, semi-supervised ML and reinforcement ML methods,
            interfaces and simple instructions .               and their applications in preprinting, printing, and
                                       [21]
                                                               postprinting. They concluded that ML can optimize printing
               As illustrated in  Figure 3b, DL methods can    parameters and bioinks, save printing time, and detect
            automatically discover underlying patterns and identify the   the anomalies. The identified bottlenecks are the limited
            most descriptive and salient features in image-recognition   amount of data and the transferability of current models,
            tasks. Feature extraction and selection steps are omitted in   since these models heavily depend on mathematical features
            this type of learning method. DL methods have achieved   of the training data and may suffer from inconsistency when
            significant success in many image application scenarios,   dealing with data from other sources.
            and convolutional neural networks  (CNN) are the most
            popular DL methods . Unlike traditional ML methods,   The aim of this work is to collect and summarize the
                             [15]
            DL methods can handle more complex tasks, such as   publications and present a state-of-the-art review, and
            classification, segmentation, and object detection, which   highlight  the  emerging  scientific  potential  of  ML  when
            require relatively large-scale datasets.           applied to bioprinting. First, ML applications in process
                                                               monitoring, printing parameters, and biomaterial/
               Traditional ML and DL methods used in bioprinting   bioink design are discussed. Second, ML applications in
            applications can also be categorized into supervised and   cell performance analysis are investigated. After that, a
            unsupervised  learning .  Supervised  ML  methods  can   literature-based analysis of challenges and outlook is given.
                              [21]
            establish mathematical models between inputs and outputs
            using labeled datasets, such as multilayer perceptron   2. ML applications in process, parameter,
            (MLP) , SVM  [22,25,26] , CNN [15,22] , and backpropagation   and material optimization
                 [24]
            neural  network  (BPNN) . Because  of the  complicated
                                [27]
            nature of images, some objects are difficult to label, such   The published papers on ML applications in bioprinting
            as nuclei, morphological phenotypes, and cell shapes   are summarized in  Table 1, along with the application
            during  proliferation  and  migration.  Unsupervised  ML   areas, specific tasks, and proposed ML algorithms.
            methods have been proposed to explore unlabeled objects   Current applications are divided into four categories:
            as patterns or clusters and to identify hidden patterns or   image analysis-based in situ process monitoring, printing
            similarities through self-taught rules [28,29] . It was believed   parameter optimization, biomaterial/bioink optimization,
            that ML applications in process optimization, dimensional   and cell performance analysis. Various properties are
            accuracy analysis, manufacturing defect detection,   considered for parameter optimization such as fiber
            and material property prediction may accelerate the   resolution, integrity of the printed constructs, cell viability
            perspectives of bioprinting development .          after extrusion and the integration of them. Even though
                                            [22]
                                                               diverse tasks are listed, the focus is on building process–
               In short, traditional ML methods are fully transparent,   material–performance models. It can be seen that both
            and researchers can transfer their insights and knowledge to   traditional ML and DL methods can be applied, and the
            domain-specific tasks. DL methods are superior in terms of   ML method selection often considers the task complexity


            Volume 9 Issue 4 (2023)                         51                           https://doi.org/10.18063/ijb.717
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