Engineering cell-alignment scaffold using organic-based nanotopography and its applications

Abstract

Granting anisotropy in cell organization has been considered significant these days as it is necessary in reproducing native tissues in our body, leading to the development of tissue engineering, regenerative therapy, and cell biology. For some tissues, the orientation of composing cells imposes a high impact on their biological function. The cellular arrangement influences the contraction/relaxation of muscle tissue, the pulsatile flow of vascular tissue, axonal regrowth of neural tissue, and the wound healing of connective tissue. Therefore, people have devoted themselves to developing a platform that can mimic or regenerate cellular orientation as in native tissues. In this thesis, we demonstrate two facile approaches to fabricate the scaffold that can harvest cells and guide their orientation simultaneously. As cells follow through the underlying geometric cues via contact guidance, topographies are generated in bottom-up and top-down methods. The bottom-up method exploits the self-assembly behavior of sublimable liquid crystal (LC). The thermal annealing process induces repetitive sublimation-recondensation, leading to the reorganization of LC molecules at the air-LC interface to form hemicylindrical nanogrooves. On the other hand, the top-down method produces nanogrooves on a substrate via the scratching technique. The diamond lapping films of which grain sizes can be controlled are scratched over various substrates, giving uniaxial nanotopography. The cells cultured on nanotopography are well aligned along with the underlying pattern, proving their outstanding performance as cell-alignment scaffolds. To further investigate the effect of nanotopography on cells, various optical measurements, qPCR experiments, and shape evaluation are performed. The cells following the underlying nanopattern exhibit different morphogenesis and gene expression. The versatility of both methods is addressed. The applicability of various cell lines, including isotropic epithelial cells and human adipose-derived stem cells (hADSC), are demonstrated on LC-based scaffold, while different types of substrates are shown to be adaptable to the scratching method. In the end, several applications such as cell sheet detachment and wound closure experiments are illustrated.