Directed vertical cell migration via bifunctionalized nanomaterials in 3D step-gradient nanocomposite hydrogels

Directional cell migration plays an important role in embryonic development, tissue regeneration, wound healing, and proper immune responses. In order to control cell migration, various gradient biomaterials have been fabricated. Although most of these systems have been designed to study cell migration in the horizontal (XY) plane, the migration of cells in the vertical plane (bottom to top: XZ) is crucial for wound healing, development of the cerebellum, and metastatic processes. In this study, we designed new step-gradient nanocomposite (NC) scaffolds by 3D printing different layers of NC hydrogels containing increasing concentrations of bifunctional nanomaterials (NMs). The synthesized bifunctional NMs are stimuli (pH) responsive and, when integrated into the 3D network of the step-gradient NC scaffolds, provide sustained release of bioactive molecules, which is beneficial for local drug delivery applications. We demonstrate that bifunctional NMs used in vertically increasing concentrations can influence the migration of cells in the XZ plane of the step-gradient NC scaffolds. Further, the bifunctional NMs improve the viability of healthy cells and promote their migration in the XZ plane of the step-gradient NC scaffolds, they simultaneously inhibit the concurrent migration and growth of cancer cells due to the pH-responsive release of bioactive molecules.