Considering that both cardiovascular disease (CVD) and congenital heart diseases (CHD) are still the leading cause of morbidity and mortality worldwide, there is a need for a robust and reliable cardiac model. Cardiac organoids are complex, three-dimensional cellular constructs that recapitulate the processes of the human embryonic heart. However, certain vital morphological features within the fetus are not yet replicable with cardiac organoids. Here we report our investigation to generate cardiac organoids with chamber formations. Our method involves modulating the Wnt pathway at two different instances while also implementing two cell seeding densities, all to determine the most optimized that to produce chamber formations within cardiac organoids.

The blood-brain barrier (BBB) is composed of brain microvascular endothelial cells (BMECs), pericytes, and astrocytic endfeet, which regulate the transport of molecules into and out of the brain. BMECs possess intrinsic barrier properties that limit the passage of approximately 98% of small molecules into the brain in healthy individuals. However, in some brain diseases, the BBB undergoes structural and functional alterations, which can contribute to disease progression. In this study, we aimed to investigate the BBB by exploring the effects of endothelial cell stretching and the optimal dimensionality of stretching to enhance endothelium barrier tightness in Chapter 2. Subsequently, we developed an endothelium gradient stretching device to further examine the stretching effect in Chapter 3. Additionally, we investigated the promotion of endothelium tightness through the use of electrospun fibers, wherein we controlled the pore size. Based on these findings, we designed and fabricated an organ chip model that incorporates mechanical stretching, microfluidic techniques, electrospun fibers, and hydrogel extracellular matrix (ECM). The results of permeability testing demonstrated that this chip significantly improved the tightness of microvascular selective transport ability and has the potential to be used in drug sorting for central nervous system (CNS) diseases.

Soft actuation methods are a developing field of robotics deemed suitable for physical human-robot interactions due to the adaptability of materials and compliant structures. Thermo-active soft actuators are a subset of these which convert thermal energy to mechanical work in the form of elongation, bending, or twisting to conform to the environment. This study is divided into three major studies that all use actuators with a working principle of phase-change fluid vaporizing for expansion with applied heat from a Peltier. The first study evaluates the bandwidth and efficiency between (i) traditional Joule heating, and (ii) Peltier heating, finding that Peltier heating can considerably improve the operational bandwidth of the actuator. The second study uses a thin membrane actuator placed in a braided mesh to form a McKibben muscle capable of lifting 5N, and formed into a gripper capable of manipulating objects within the environment. The third study uses actuators of a solid, hollow and flexible Peltier embedded silicone structure and are evaluated and optimized in order to increase actuation speed, finding that the embedded flexible Peltier design was able to elongate over 50% of its original height in 20 seconds. The overall aim of all of these studies was to …