14–17 Sept 2025
Palace of Culture and Science
Europe/Warsaw timezone

Programming degradation of sacrificial microgels to direct cellular function

Speaker

Khoon Lim (University of Sydney)

Description

Porous scaffolds are fundamental components in the field of tissue engineering and regenerative medicine, serving as essential frameworks that support and guide the growth, attachment, and proliferation of cells. These scaffolds mimic the natural extracellular matrix, providing a three-dimensional environment conducive to tissue development. One of the most critical features of these scaffolds is their porosity, which directly influences nutrient diffusion, waste removal, and cellular migration. The degree and nature of porosity can be finely tuned through various parameters, including the size of sacrificial materials, their volumetric ratios, and the temporal architecture embedded within the scaffold structure. These design elements not only determine the initial physical characteristics of the scaffold but also influence how it evolves over time in response to biological processes.

In this study, we propose that the materials used to create porosity within scaffolds can significantly affect cellular behavior over extended periods. To explore this hypothesis, a flow-focusing microfluidic system was employed to fabricate gelatin-based microgels with precise spatial and temporal control. These microgels were then incorporated into Gelatin Methacryloyl (GelMA) hydrogels to introduce dynamic porosity. This approach allowed for the creation of microporous networks that could evolve over time, facilitating enhanced cell migration and proliferation.
The microfluidic system enabled meticulous control over the size distribution of the gelatin microgels, which is crucial for achieving uniform and predictable porosity within the hydrogel matrix. Furthermore, the degradation rate of these microgels was modulated using dityrosine crosslinks, which were formed through a visible light-induced reaction involving a ruthenium/sodium persulfate co-initiator system. By adjusting variables such as the order of fabrication steps, the concentration of initiators, and the polymer content, we were able to fine-tune the degradation profiles of the microgels, thereby controlling the temporal evolution of porosity within the scaffold.

The biocompatibility of the gelatin microgels was validated through in vitro experiments using human dermal fibroblasts (HDFs) and human mesenchymal stromal cells (HMSCs). Over a seven-day culture period, the microgels supported robust cell adhesion, viability, and proliferation. When these microgels were encapsulated within GelMA hydrogels, they created a delayed microporous structure that significantly enhanced cellular activity compared to bulk GelMA hydrogels without microgels. The composite scaffolds demonstrated superior performance in terms of cell viability, proliferation, and intercellular interactions, highlighting the advantages of incorporating biodegradable microgels into hydrogel matrices.

Overall, this research underscores the potential of using biodegradable gelatin microgels to engineer dynamic, cell-responsive porous scaffolds. Such scaffolds not only provide initial structural support but also adapt over time to meet the evolving needs of regenerating tissues. This approach represents a promising strategy for advancing tissue regeneration by creating more physiologically relevant and responsive biomaterials.

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