Browsing by Subject "Microgels organ-on-chips"

Now showing 1 - 1 of 1

Embargo
Capturing the dynamic scaffold properties of hybrid GelMA based microgels toward tissue engineering and organ-on-chips
(2024-09) Çınar, Aslı Gizem
Microgels have emerged as versatile materials in tissue engineering, drug delivery, and organ-on-chip (OoC) platforms due to their small scale, uniformity, and customizable properties. Their adaptability as injectable materials and dynamic scaffolds makes them promising candidates for a wide range of biomedical applications. However, traditional methods for characterizing their physical and mechanical behaviors, designed for bulk hydrogels, do not capture the unique properties of microgels, which differ significantly in terms of size and surface-to-volume ratio. This work explores the physical properties of Gelatin Methacryloyl (GelMA)-based Collagen and Hyaluronic Acid Methacrylate (HAMA) hybrid microgels produced via droplet microfluidics, employing novel assays tailored specifically to their micro-scale. Real-time observation of their swelling and degradation properties is carried out using a custom-made platform enabling the tracking of individual microgels, and electron microscopy provides insights into their internal structures, revealing previously unobserved behaviors. We have shown the interpenetrating network formation when GelMA and Collagen are used; and copolymer formation when GelMA and HAMA are used. Under the effect of Collagenase and Hyaluronidase, the individual microgels showed different degradation mechanisms, which have proven to be affected by crosslink densities, enzyme-substrate specificity, enzyme saturation, and properties of the individual network components. The work is extended by focusing more on the temporal profiling of GelMA and HAMA hybrid microgels' behaviors under enzymatic degradation, examining how volume, mechanical properties, and surface features evolve over time, simulating the dynamic conditions encountered in vivo during especially tissue engineering applications. We found that instead of carrying out separate assays to understand the changes, a more holistic approach to evaluating the aforementioned properties gives a more thorough discussion. This approach revealed that changing the ratios of GelMA against HAMA affects the crosslink densities, network formation, and ultimately degrative behaviors. We have observed, for the first time in droplet microfluidics, that a certain combination of GelMA HAMA results in microgels with a network gradient, getting denser towards the center, while the other combinations only increased the crosslink densities without altering the porous homogeneity. Furthermore, the number of microgels exposed to the same concentration of enzyme is altered to emulate different injection volumes into similar tissues, or the enzyme concentration is altered to emulate injection into different tissues. These assays showed the sensitivity of degradation profiles against enzyme saturation and competition. Meanwhile, the stiffness and surface morphology changes of microgels during degradation are examined, revealing the importance of network homogeneity in presenting stable mechanical properties during degradation. Lastly, drug release from these scaffolds is modeled for prospective applications, and their relation to scaffold properties is evaluated. Overall, this thesis is poised to discover the peculiar behaviors of GelMA hybrid microgels produced with droplet microfluidics uncovering the importance of carrying out investigations true to the sample at hand and the conditions that will be imposed upon them during application.