Photo-Triggered Hyaluronic Acid Hydrogel for 3D Culture and Cell Recovery

Properties of semisynthetic hydrogels can be fine-tuned, making these attractive for various applications in regenerative medicine. Herein, a hydrogel platform based on hyaluronic acid (HA) modified by (1R, 8S,9S)-bicycle[6.1.0]non-4-yn-9-ylmethanol (BCN) and a cross-linker composed of light-sensitive o-nitrobenzyl and polyethylene glycol (PEG) chains terminating in azides is described. The two components can undergo strain-promoted azide-alkyne cycloaddition resulting in rapid gel formation. First, adipose-derived mesenchymal stromal cells (MSCs) are incorporated in the hydrogel and it is demonstrated that the cells can be easily retrieved by UV light-mediated degradation, maintaining viability and retaining spindle-like shape when the cells are replated. Next, a proof-of-concept of inducing light-mediated softening of the hydrogel to modulate the morphology of the encapsulated cells is provided. A co-culture of endothelial cells (cord blood-derived endothelial colony forming cells and bone marrow-derived MSCs), which is commonly studied for their ability to form capillary-like vascular networks, is cultured in the regular and light-induced softened hydrogels. Nonphotoexposed hydrogels show cells with a prevalently rounded morphology, whereas stretched cells connecting into a primitive capillary network are observed in the light-softened hydrogels. Photo-induced softening offers potential to locally control cell shape and self-organization capacity.