Hydroxyapatite nanoparticle films with designed nanostructures for advanced cell culture

Tissue engineering technology can be used to reconstruct biological tissues or organs with lesions or loss of function and minimize the damage to patients during the repair process. As an important and fundamental component of tissue engineering, the development of cell culture technology has attracted widespread attention. In particular, the design of cell culture substrates that can provide good cell culture properties has been extensively studied. The main commercially available culture substrate is tissue culture polystyrene (TCPS), but the survival rate of cells cultured on TCPS after in vivo transplantation is relatively low, which is considered to result from the environmental differences in composition and structure between TCPS and biological tissues. Accordingly, we summarized the current status of cell culture, the issues associated with culture substrates, and the conditions required for good cell culture substrates. In particular, the culture substrate needs to be highly transparent for optical microscopy. Moreover, since cell adhesion occurs by recognizing the proteins adsorbed on the substrate, it is proposed to control the protein adsorption state through nanostructures. Thus, hydroxyapatite (HA) with good biocompatibility has attracted attention, and its properties and the possibility of forming a transparent nanostructured film have been summarized. Furthermore, based on the inorganic-organic composite structures in living bodies, such as bone tissue, the coordination between HA nanoparticles and organic citric acid molecules has also been considered to fabricate functional films for producing new cell culture substrates with a wider range of applications. In this review, the basis of cell culture technology is systematically explained, and the design concepts of culture substrate surfaces for achieving favorable cell culture properties are highlighted. Surface functionalization of HA nanoparticle films is proposed to enhance protein adsorption and cell adhesion, and is expected to have wide applications in the field of regenerative medicine.