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

Xiaohong Wang,Chang Liu

doi:10.3390/polym10101048

Abstract

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.

Highlights

There are about 78 organs in a human body [1]
After the fibrinogen molecules were polymerized with the thrombin solution, cells (i.e., adipose-derived stem cells (ADSCs) and hepatocytes) were immobilized in different layers of the fibrin hydrogels and the cell-laden fibrin hydrogels took the shape of membranes (Figure 2c)
Two different cell types, including ADSCs and hepatocytes, are arranged into specific locations in the predesigned spindle construct through the Weissenberg effect of a cell-laden non-Newtonian fibrinogen fluid

Summary

Introduction

There are about 78 organs in a human body [1]. Each of the organs consists of multiple heterogeneous tissues. Visceral organs, such as the liver, heart, kidney and lung, are essential for human survival. The liver is the largest digestive organ in the human body. In contrast to the structural or sensorial (or sensory) organs, such as bone, cartilage and skin, the liver carries out more than hundreds of metabolic functions, such as synthesis, transformation and excretion. Acute liver failure remains a disease with very high mortality [2]. The severely limited donor supply, the lifelong immune exclusion reaction and the extremely high transplantation cost have stimulated continuing efforts to manufacture implantable bioartificial livers with a predesigned vascular network [3,4,5,6,7,8]

Methods

Results

Discussion

Conclusion