Developing materials for tissue engineering and studying the mechanisms of cell adhesion is a complex and multifactor process that needs analysis using physical chemistry and biology. The major challenge is the labor-intensive data mining as well as requirements of the number of advanced techniques. For example, hydrogel-based biomaterials with cell-binding sites, tunable mechanical properties, and complex architectures have emerged as a powerful tool to control cell adhesion and proliferation for tissue engineering. Composite hydrogels could be used for bone tissue regeneration, but they exhibit poor ossification properties. In current work, we have designed new osteoinductive gellan gum hydrogels by a thermal annealing approach and consequently functionalized them with Ca/Mg carbonate submicron particles. Determination of key parameters, which influence a successful hydroxyapatite generation, was done via the principal component analysis of 18 parameters (Young's modulus of the hydrogel and particles, particle size, and mass) and cell behavior at various time points (like viability, numbers of the cells, rate of alkaline phosphatase production, and cells area) obtained by characterizing such composite hydrogel. It is determined that the particles size and concentration of calcium ions have a dominant effect on the hydroxyapatite formation, because of providing local areas with a high Young's modulus in a hydrogel, a desirable property for cell adhesion. The detailed analysis presented here allows identifying hydrogels for cell growth applications, while on the other hand, material properties can be predicted, and their overall number can be minimized leading to efficient optimization of bone reconstruction and other cell growth applications.
Keywords: hydrogels; mineralization; ossification; particles; principal component analysis.