Shape-defining alginate shells as semi-permeable culture chambers for soft cell-laden hydrogels

Abstract

Soft hydrogels have a porous structure that promotes viability and growth of resident cells. However, due to their low structural stability, these materials are fragile and difficult to culture in vitro. Here we present a novel approach for the 3D culture of such materials, where a shape-defining, semi-permeable hydrogel shell is used to provide mechanical stability. These thin hydrogel shells enclose and stabilize the soft materials while still permitting gas and nutrient exchange. Custom alginate-shaped shells were prepared using a thermosetting, ion-eluting hydrogel mold. In a second step, the hydrogel shells were filled with cell-laden infill materials. As an example of the versatility of this technique, materials previously not available for tissue engineering, such as non-annealed microgels or low crosslinked and mechanically unstable hydrogels, were used for tissue culture. Primary human chondrocytes were cultured using this platform, to evaluate its potential for cartilage tissue engineering. To prove the scalability of this technique, anatomically-shaped ears were cultured for 3 weeks. This novel approach has the potential to radically change the material property requirements in the field of tissue engineering: thanks to the shape definition and stability provided by the hydrogel shells, a wide range of materials previously inaccessible for the manufacture of 3D tissue grafts can be re-evaluated.