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

Abstract

Properties of semi-synthetic hydrogels can be fine-tuned making these attractive for various applications in regenerative medicine. Here, we describe 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. The two components can undergo strain-promoted azide-alkyne cycloaddition (SPAAC) resulting in rapid gel formation. First, we incorporated adipose-derived mesenchymal stromal cells (aMSCs) in the hydrogel and demonstrated that the cells can be easily retrieved by UV light mediated degradation maintaining viability and retaining spindle-like shape when the cells were replated. Next, we provided a proof-of-concept of inducing light-mediated softening of the hydrogel to modulate the morphology of the encapsulated cells. A co-culture of endothelial cells (cord blood-derived endothelial colony forming cells (ECFCs) and bone marrow derived mesenchymal stromal cells (bmMSCs), which are commonly studied for their ability to form capillary-like vascular networks, were cultured in the regular and light induced softened hydrogels. Non-photoexposed hydrogels showed cells with a prevalently rounded morphology, whereas stretched cells connecting into a primitive capillary network were observed in the light-softened hydrogels. Photo-induced softening offers potential to locally control cell shape and self-organization capacity.