Yao‑Nan Wanga, Ko‑Tung Changb, Jui‑Kai Liuc, Chang‑Hsien Taid*
aDepartment of Vehicle Engineering, National Pingtung University of Science and Technology, Pingtung, Taiwan, bDepartment of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung, Taiwan, cGeneral Research Service Center, National Pingtung University of Science and Technology, Pingtung, Taiwan, dMaster Program in Sustainability and Disaster Management, Tzu Chi University, Hualian, Taiwan
Open Access funded by Buddhist Compassion Relief Tzu Chi Foundation
Abstract
Cell culture technologies are fundamental tool in biological research. Traditional two‑dimensional (2D) cell culture methods, despite their widespread use and simplicity, fail to accurately replicate the physiological conditions of native tissues, leading to altered cellular behavior. Recent advancements in 3D culture techniques, combined with innovative fabrication methods such as photolithography, paper‑based, and 3D printing, have substantially improved the fidelity of cell culture models. In parallel, numerical simulations have become indispensable for optimizing the design and performance of these systems, offering precise control microenvironmental factors such as fluid dynamics, nutrient and oxygen gradients, and shear stress within microfluidic platforms. These approaches for integration facilitate accurate modeling of cell‑to‑cell and cell‑to‑matrix interactions essential for physiological relation. Concurrently, the integration of multimaterial fabrication techniques provides scalable and customizable solutions for developing sophisticated microfluidic and cell culture systems. This review discusses recent developments in these fabrication methods and highlights their integration with numerical simulation for optimization design, explores their collective potential to advance biomedical research and applications.
Keywords: Cell culture, Lithography, Numerical simulation, Paper‑based, Three‑dimensional printing
