Fibrin Hydrogels for Endothelialized Liver Tissue Engineering with a Predesigned Vascular Network

The design and manufacture of a branched vascular network is essential for bioartificial organ implantation, which provides nutrients and removes metabolites for multi-cellular tissues. In the present study, we present a technology to manufacture endothelialized liver tissues using a fibrin hydrogel and a rotational combined mold. Both hepatocytes and adipose-derived stem cells (ADSCs) encapsulated in a fibrin hydrogel were assembled into a spindle construct with a predesigned multi-branched vascular network. An external overcoat of poly(dl-lactic-co-glycolic acid) was used to increase the mechanical properties of the construct as well as to act as an impervious and isolating membrane around the construct. Cell survivability reached 100% in the construct after 6 days of in vitro culture. ADSCs in the spindle construct were engaged into endothelial cells/tissues using a cocktail growth factor engagement approach. Mechanical property comparison and permeability evaluation tests all indicated that this was a viable complex organ containing more than two heterogeneous tissue types and a functional vascular network. It is, therefore, the first time an implantable bioartificial liver, i.e., endothelialized liver tissue, along with a hierarchical vascular network, has been created.