(165x) Regulation of Stem Cell Spheroid Function in Gelatin Methacryloyl Hydrogel with Different Mechanical Properties for 3D Tissue Engineering

Hydrogel which has properties similar to the extracellular matrix (ECM), such as 3D network structure, high water contents, and elastic properties has been applied in tissue engineering for regeneration of damaged tissue. The various biomaterials (collagen, hyaluronic acid (HA), etc.) have been used for hydrogel, in particular, gelatin methacryloyl (GelMA), which has cell adhesion moieties and mild crosslinking condition (room temperature (RT), neutral pH) has recently been in the spotlight. Cell spheroids which maintain intensive cell-to-cell interaction have high viability, cytokine release (pro-angiogenic, anti-inflammatory), and differentiation efficiency, so that spheroid encapsulation was employed in tissue engineering due to expectation of overcoming indirect cell-cell interaction. Despite several reports, the studies on the effect of hydrogel mechanical properties on spheroids are insufficient compared to the study on cells encapsulated hydrogel. Particularly, the functionality of stem cell spheroids within GelMA-based soft hydrogel (< 1 kPa) that can be applied for a variety of applications has not been identified yet.

In this study, the effect of hydrogel mechanical properties on stem cell spheroids was investigated for the applying of spheroids encapsulated hydrogel in 3D tissue engineering. To this end, stem cell spheroids having a defined size were prepared, and spheroid-laden hydrogels were fabricated with various mechanical properties (0.3 - 2 kPa). Then, the effect of mechanical properties on the morphology and spheroid functionality (migration, apoptosis, proliferation) was investigated. Finally, the osteogenesis and angiogenesis of spheroids encapsulated in hydrogel were confirmed to investigate the potential of 3D tissue construction of spheroid-laden hydrogel.