The Optimization of Culture Conditions for Injectable Recombinant Collagen Hydrogel Preparation Using Machine Learning

Injectable recombinant collagen hydrogels (RCHs) are crucial in biomedical applications. Culture conditions play an important role in the preparation of hydrogels. However, determining the characteristics of hydrogels under certain conditions and determining the optimal conditions swiftly still remain challenging tasks. In this study, a machine learning approach was introduced to explore the correlation between hydrogel characteristics and culture conditions and determine the optimal culture conditions. The study focused on four key factors as independent variables: initial substrate concentration, reaction temperature, pH level, and reaction time, while the dependent variable was the elastic modulus of the hydrogels. To analyze the impact of these factors on the elastic modulus, four mathematical models were employed, including multiple linear regression (ML), decision tree (DT), support vector machine (SVM), and neural network (NN). The theoretical outputs of NN were closest to the actual values. Therefore, NN proved to be the most suitable model. Subsequently, the optimal culture conditions were identified as a substrate concentration of 15% (W/V), a reaction temperature of 4 °C, a pH of 7.0, and a reaction time of 12 h. The hydrogels prepared under these specific conditions exhibited a predicted elastic modulus of 15,340 Pa, approaching that of natural elastic cartilage.