Evaluation of the hydrogels Matrigel, Biogelx, PLTMAx and GelMA in the generation of minilungs from human embryonic stem cells (hESC)

Organoids isolated from adult cells and, especially, those synthesized from human pluripotent stem cells, both induced (hiPSCs) or embryonic stem cells, (hESCs), offer unique opportunities for disease modeling, drug testing or organ replacement (regenerative medicine). The biofabrication of functional tissue require supportive biomaterials and scaffolds generated from reliable materials. Due to the murine origin of the market choice hydrogel (Matrigel), its suitability for regenerative medicine or clinical translation is greatly limited. Thus, the development of new supportive materials for long-term cell survival and differentiation of pluripotent stem cells which are biocompatible with clinical translation and automatized synthesis, or bioprinting, is an urgent need. In the present study, we have evaluated the suitability of four representative hydrogels, also fitting as bioinks, as supportive biomaterials for cell growth and differentiation of respiratory organoids or minilungs from hESCs. The hydrogels Biogelx, PLTMax and GelMA, were evaluated in the generation of minilungs in parallel to Matrigel. In contrast to those in Matrigel, the minilungs embedded into the hydrogels tested were smaller, less branched or fragmented. The minilungs showed the expression of three surfactant proteins, despite exhibiting abnormal structures. The aberrant cell growth and cellular arrangement observed suggest that these promising hydrogels or bioinks tested might not be biocompatible for organoid differentiation and for establishing future strategies based on automatized synthesis or bioprinting of lung tissue.