Hierarchical TiO2 nanotube arrays enhance mesenchymal stem cell adhesion and regenerative potential through surface nanotopography.

The concept of preconditioning mesenchymal stem cells (MSCs) under different stress conditions or with bioactive molecules is introduced to optimize their therapeutic potential. This study investigates the physicochemical effect of hierarchical TiO₂ nanotube arrays, a versatile and easy-to-prepare nanosurface, on MSC behaviour. By precisely controlling the nanotopography through anodization, we demonstrate the significant influence of surface properties on MSC adhesion, proliferation and differentiation. Electrostatic interactions between surface charge and proteins play a crucial role in these cellular responses. In addition, preconditioning MSCs under specific conditions enhances their therapeutic potential by optimizing paracrine signalling and homing properties. Higher surface charges and increasing spiky character of surface roughness of titania samples after anodization at 60 V significantly upregulated chemokine receptor type 4 (CXCR4) and vascular endothelial growth factor A (VEGFA), indicating the enhanced migratory and angiogenic potential of MSCs. The study reveals the mechanotransductive effects of nanotopography on MSC differentiation, suggesting that tailored surface features can direct cellular fate. These findings highlight the potential of hierarchical TiO₂ nanotube arrays as a promising platform for regenerative medicine, offering a novel approach to improve tissue engineering and therapeutic outcomes.