Abstract
This proposal addresses critical challenges in cell encapsulation, dynamic tissue culturing, and vascular regeneration through the application of advanced microfluidic technologies. In cell encapsulation, optimizing nutrient and oxygen delivery to minimize hypoxia-induced cell death remains a major challenge. To tackle this, the study employs computational modeling and fluid dynamics to design a droplet generation approach from which provides precise control of the multi-phase flow, enhancing cell viability and functionality. In dynamic tissue culture, ensuring consistent and accurate mechanical forces on intervertebral discs (IVDs) over extended periods poses a significant challenge. To address this, an Arduino-based control system and a mechanical loading unit have been developed. By integrating a calibrated loading regimen, low-profile force sensors, and computational force distribution modeling, the Disc-on-a-ChipMF platform, coupled with a customized microfluidic IVD culture chamber, effectively maintains controlled mechanical forces for a 21-day ex vivo IVD culture. Building on the previous studies, the research then focuses on vascular regeneration, understanding how spatial and cellular factors influence angiogenesis. A novel microfluidic system is developed to replicate the in-vivo angiogenic environment, enabling precise studies of how the spatial distribution and density of human lung fibroblasts affect endothelial cell behavior during angiogenesis. The system also models pro-angiogenic growth factor gradients using live-cell fluorescence imaging, which provides guidance for future in vitro vascularization studies. Additionally, the study aims to integrate cell encapsulation techniques to localize mesenchymal stem cells (MSCs) and islets within the microfluidic platform, examining angiogenic cues influence stem cell differentiation and islet insulin secretion functionality. The contributions of this research lie in the development of scalable, reproducible microfluidic platforms, offering significant potential to enhance therapeutic strategies for diabetes treatment, spinal disc degeneration, and vascular tissue regeneration through precisely engineered in vitro models.