Effects of Permeability and Living Space on Cell Fate and Neo-Tissue Development in Hydrogel-Based Scaffolds: A Study With Cartilaginous Model

One bottleneck in tissue regeneration with hydrogel scaffolds is the limited understanding of the crucial factors for controlling hydrogel's physical microenvironments to regulate cell fate. Here, the effects of permeability and living space of hydrogels on encapsulated cells' behavior were evaluated, respectively. Three model hydrogel‐based constructs are fabricated by using photo‐crosslinkable hyaluronic acid as precursor and chondrocytes as model cell type. The better permeable hydrogels facilitate better cell viability and rapid proliferation, which lead to increased production of extracellular matrix (ECM), e.g. collagen, glycosaminoglycan. By prolonged culture, nano‐sized hydrogel networks inhibit neo‐tissue development, and the presence of macro‐porous living spaces significantly enhance ECM deposition via forming larger cell clusters and eventually induce formation of scaffold‐free neo‐tissue islets. The results of this work demonstrate that the manipulation and optimization of hydrogel microenvironments, namely permeability and living space, are crucial to direct cell fate and neo‐tissue formation. The effects of permeability and living space of hydrogel scaffolds on cell fate and neo‐tissue development are studied, respectively. The better permeability of hydrogel facilitates cell survival and rapid proliferation. The presence of macro‐porous living spaces favors the formation of larger cell clusters, which significantly enhance extracellular matrix deposition and eventually induce formation of neo‐tissue.