Photo-crosslinked gelatin methacrylate hydrogels with mesenchymal stem cell and endothelial cell spheroids as soft tissue substitutes

Tumors, trauma, and congenital defects require volume restoration of soft tissues. Tissue engineering provides an alternative source for substituting these defects. Cell encapsulation into hydrogels provides a three-dimensional microenvironment. Spheroids of cells provide close packing and increase cell-to-cell contacts resulting in differentiation. Gelatin is a natural polymer with low immunogenicity and preserved amino acid motifs for cell adhesion and proliferation. In the present study, a soft photo-crosslinked gelatin methacrylate (GelMA) hydrogel with long in vitro lifetime was synthesized. Stem cells (dental pulp derived, DPSC) and endothelial cells (umbilical cord derived, HUVEC) were formed into spheroids to induce prevascular network formation and encapsulated into GelMA (10% weight/volume). Results showed high cell viability, better gel mechanical properties, and longer HUVEC sprouting with spheroids compared to the same combination of cells. Altogether, the photo-crosslinked GelMA hydrogels with DPSC and HUVEC spheroids provided a promising tissue engineering and vascularization strategy in vitro.