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Differentiating Cardiac Organoids with Chamber Formations

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.
Date: July 2023
Creator: Seddoh, Percyval Prince-Danny
System: The UNT Digital Library
Modeling of Hypertrophic Cardiomyopathy Using hiPSC-Derived Cardiomyocytes with Static Mechanical Stretching (open access)

Modeling of Hypertrophic Cardiomyopathy Using hiPSC-Derived Cardiomyocytes with Static Mechanical Stretching

The heart is a dynamic environment that is constantly experiencing some degree of remodeling from the point of development, all the way through adulthood. While many genetic components may contribute to the overall presentation of hypertrophic cardiomyopathy (HCM), mutations occurring in sarcomere components such as myosin binding protein C3 (MYBPC3) are of the greatest popularity for study. Aiming to understand the mechanisms underlying heart diseases and to develop effective treatments that circumvent the need for direct patient study, we investigated the use of a platform to mimic the unique physiological conditions of HCM within an in-vitro setting. Following the induction of mechanical stretch on three human induced pluripotent stem cell derived cardiomyocyte (hiPSC-CM) cell lines containing mutations for MYBPC3 (WT, HET, HOM), all displayed HCM like reactions in calcium waveform. In conclusion, this system demonstrated the potential to apply a constant, static strain to healthy and mutated hiPSC-CMs for the MYBPC3 protein to model HCM in-vitro.
Date: May 2023
Creator: Rogozinski, Nicholas
System: The UNT Digital Library

Novel Phase-Chance Soft Actuators Controlled via Peltier

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 …
Date: July 2023
Creator: Johnson, Daniel Cody
System: The UNT Digital Library

Mesenchymal Stem Cells Encapsulated and Aligned in Self-Assembling Peptide Hydrogels

This study presents a viable strategy using fmoc-protected peptides hydrogels, to encapsulate and stretch mesenchymal stem cells (MSC). To explore the peptide hydrogel potential, a custom mechanical stretching device with polydimethylsiloxane (PDMS) chambers were used to stretch MSCs encapsulated in Fmoc hydrogels. We investigated the impact of fmoc- FF prepared in dimethyl sulfoxide (DMSO), 1,1,1,3,3,3-hexafluoro-2-propanol (HFP) and deionizied water in the self-assembly, and mechanical properties of the gels. The peptide hydrogel is formed through molecular self-assembly of peptide sequence into β-sheets that are connected with the π-π aromatic stacking of F-F groups. The hydrogels provided a stiff, hydrated gel with round nanofiber morphology representing an elastic modulus of 174-266 KPa. MSCs cultured on peptide hydrogels undergo viability, morphology, and alignment evaluations using MTT, live/dead, and phalloidin (F-actin) staining. The F-actins of 3D- cultured MSCs in Fmoc-FF/HFP, and Fmoc-FF/DMSO followed by mechanical stretching showed elongated morphology with defined microfilament fibers compared to the round and spherical F-actin shape of the control cells. Peptide gels with 5mM concentration preserved 100% viability of MSC. Results reveals the feasibility and conditions for successful cell encapsulation and alignment within peptide hydrogels. Encapsulation of MSC in peptide nanofiber followed by a stretching process present a promising …
Date: December 2023
Creator: Kasani, Yashesh Varun
System: The UNT Digital Library

Magnetoresponsive Layer-by-Layer (LBL) Polyelectrolyte Microcapsules Exposed to Low Frequency Alternating Magnetic Field for Drug Delivery to Breast Cancer Cells

Layer-by-layer (LBL) polyelectrolyte capsules can be modified to incorporate stimuli such as superparamagnetic nanoparticles which respond to a magnetic field only when it is turned on. Thus, they can act as a switch to load or unload their drug cargo on demand. Specifically, magnetite is incorporated into bilayer capsules made of alternating poly(allylamine hydrochloride) (PAH) and poly(sodium-p-styrenesulfonate) (PSS) which surrounds calcium carbonate core. The core is then dissolved using ethylenediaminetetraacetic acid (EDTA). These capsules are loaded with at FITC-BSA conjugate and examined with fluorescence to show the unloading of the FITC-BSA from capsules as it brightens the entire field of view of the microscope. The results suggest that we can next load and unload an anticancer drug such as doxorubicin using the combination of microcapsule and alternating magnetic field (AMF) to treat the cancer cells. Preliminary data interprets that the low frequency AMF we use has little to no adverse effect cells viability. This coincides with the general thought that low frequency AMF signals are not harmful to humans. Therefore, as an alternative to hyperthermia methods which use heat, it may be possible to deliver the anticancer drugs specifically to the cells when and where it is needed.
Date: December 2023
Creator: Powell, Robert Darrel
System: The UNT Digital Library