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Figure 1. (A) A spheroid formed by hepatocyte and HSCs. (B) Transmission electron micrograph of a hepatocyte and HSC spheroid demonstrating differentiated hepatic ultrastructure, with TJs and primitive BC. (C) Scanning electron micrograph of a nonsurface enhanced microporous poly(dl-lactic acid) scaffold seeded with activated HSCs. By producing extracellular matrix, the HSCs can attach to the polymer despite its low surface adhesion strength. BC: Bile cannaliculi; HSC: Hepatic stellate cell; TJ: Tight junction.
(Figure omitted. See article PDF.)
Liver disease is a major cause of morbidity and mortality worldwide. In the USA alone it affects 25 million patients, and results in over 25,000 deaths per year [101]. There are only a limited number of therapies available, no reliable liver support system exists and a chronic shortage of donor tissue means that liver transplantation cannot be an option for everyone. Therefore, it is imperative that regenerative medicine strategies are explored.
The concept of engineering liver tissue is very challenging due to the structural and functional complexity of the tissue. The liver has an elaborate architecture, provides a wide range of metabolic functions and consists of several cell types. Ex vivo regeneration of such a complex organ will require a much greater understanding of liver cell biology and the development of complex environments within bioreactors and scaffolds to mimic the multiple regenerative cues that are present within the body.
Scaffolds are natural or synthetic constructs that are used to direct, supplement or replace the function of living tissues [1]. In the context of liver tissue engineering, these may be used to support a liver cell population or to assist healing in a diseased or damaged liver. The concept of using a scaffold as a 3D supporting template for tissue regeneration has been successfully demonstrated in numerous applications including the repair of bone [2], cartilage [3] and vascularized skeletal muscle [4]. This review sets out to explore how these scaffolds may develop a role in liver tissue engineering. For descriptive purposes, studies have been grouped into in vitro and in vivo approaches.
In vitro liver tissue engineering
The main aim of in vitro liver tissue engineering is to sustain a functional liver cell population. An isolated hepatocyte grown in a monolayer rapidly dedifferentiates and dies [5]. This occurs...