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The field of tissue engineering has made significant advancements with extrusion-based bioprinting, which uses shear forces to create intricate tissue structures. However, the success of this method heavily relies on the rheological properties of bioinks. Most bioinks use shear-thinning. While a few component-based efforts have been reported to predict the viscosity of bioinks, the impact of shear rate has been vastly ignored. To address this gap, our research presents predictive models using machine learning (ML) algorithms, including polynomial fit (PF), decision tree (DT), and random forest (RF), to estimate bioink viscosity based on component weights and shear rate. We utilized novel bioinks composed of varying percentages of alginate (2–5.25%), gelatin (2–5.25%), and TEMPO-Nano fibrillated cellulose (0.5–1%) at shear rates from 0.1 to 100 s−1. Our study analyzed 169 rheological measurements using 80% training and 20% validation data. The results, based on the coefficient of determination (R2) and mean absolute error (MAE), showed that the RF algorithm-based model performed best: [(R2, MAE) RF = (0.99, 0.09), (R2, MAE) PF = (0.95, 0.28), (R2, MAE) DT = (0.98, 0.13)]. These predictive models serve as valuable tools for bioink formulation optimization, allowing researchers to determine effective viscosities without extensive experimental trials to accelerate tissue engineering. 

Abstract Current research practice for optimizing bioink involves exhaustive experimentation with multi-material composition for determining the printability, shape fidelity and biocompatibility. Predicting bioink properties can be beneficial to the research community but is a challenging task due to the non-Newtonian behavior in complex composition. Existing models such as Cross model become inadequate for predicting the viscosity for heterogeneous composition of bioinks. In this paper, we utilize a machine learning framework to accurately predict the viscosity of heterogeneous bioink compositions, aiming to enhance extrusion-based bioprinting techniques. Utilizing Bayesian optimization (BO), our strategy leverages a limited dataset to inform our model. This is a technique especially useful of the typically sparse data in this domain. Moreover, we have also developed a mask technique that can handle complex constraints, informed by domain expertise, to define the feasible parameter space for the components of the bioink and their interactions. Our proposed method is focused on predicting the intrinsic factor (e.g. viscosity) of the bioink precursor which is tied to the extrinsic property (e.g. cell viability) through the mask function. Through the optimization of the hyperparameter, we strike a balance between exploration of new possibilities and exploitation of known data, a balance crucial for refining our acquisition function. This function then guides the selection of subsequent sampling points within the defined viable space and the process continues until convergence is achieved, indicating that the model has sufficiently explored the parameter space and identified the optimal or near-optimal solutions. Employing this AI-guided BO framework, we have developed, tested, and validated a surrogate model for determining the viscosity of heterogeneous bioink compositions. This data-driven approach significantly reduces the experimental workload required to identify bioink compositions conducive to functional tissue growth. It not only streamlines the process of finding the optimal bioink compositions from a vast array of heterogeneous options but also offers a promising avenue for accelerating advancements in tissue engineering by minimizing the need for extensive experimental trials. 

Abstract Three-dimensional (3D) bio-printing is a rapidly growing field attempting to recreate functional tissues for medical and pharmaceutical purposes. The printability of multiple materials encapsulating various living cells can take this emerging effort closer to tissue regeneration. In our earlier research, we designed a Y-like nozzle connector system capable of switching materials between more than one filament with continuous deposition. The device had a fixed switching angle, was made from plastic, and was suitable for one-time use. This paper presents the extension of our previously proposed nozzle system. We considered 30°, 45°, 60°, and 90° angles (vertical and tilted) between the two materials and chose stainless steel as a material to fabricate those nozzle connectors. The overall material switching time was recorded and compared to analyze the effects of those various angles. Our previously developed hybrid hydrogel (4% Alginate and 4% Carboxymethyl Cellulose, CMC) was used as a test material to flow through the nozzle system. These in-house fabricated nozzle connectors are reusable, easy to clean, and sterile, allowing smooth material transition and flow.