Nanoimprint Lithography for Collagen Micropatterning at Low-Temperature 5℃ with TiO2-SiO2 Gas-Permeable Porous Mold

In tissue engineering and regenerative medicine, scaffold micropatterning plays an essential role in reproducing the microscopic cellular environment and cell-cell interactions. This study provides a novel molding process for surface microfabricaion of 100% pure fish-derived collagen without the use of photoinitiators, which can be cytotoxic, by low-temperature molding at 5℃ using nanoimprint lithography. TiO2-SiO2 gas-permeable porous mold was used to fabricate collagen micropatterns, which can improve gas entrapment during molding, one of the challenges in nanoimprint lithography. The excellent gas permeability of TiO2-SiO2 gas-permeable porous mold enabled fine patterning with a height of 80 μm and a bottom diameter of 40 μm without molding defects for a collagen solution containing 40 wt% water. FT-IR spectral measurements revealed that low-temperature drying at 5℃ during microfabrication to the collagen surface had almost no effect on the collagen components. This molding process, which does not require chemical modification of collagen and does not cause protein denaturation even at molding temperatures of 5℃, has the potential to be widely used as a next-generation medical application technology in the fields of tissue engineering and regenerative medicine.