Liver Tissue Engineering as an Emerging Alternative for Liver Disease Treatment

Abstract

Chronic liver diseases affect thousands of lives throughout the world every year. The shortage of liver donors for transplantation has been the main driving force to employ alternative methods such as liver tissue engineering (LTE) in fabricating a three-dimensional transplantable liver tissue or enhancing cell delivery techniques alleviating the need for liver donors. LTE consists of three components, cells, ECM (extracellular matrix), and signaling molecules, which we discuss the first and second. The three most common cell sources used in LTE are human and animal primary hepatocytes, and stem cells for different applications. Two major categories of ECM are used to mimic the microenvironment of these cells, named scaffolds and microbeads. Scaffolds have been made by numerous methods with a wide range of synthetic and natural biomaterials. Cell encapsulation has also been utilized by many polymeric biomaterials. To investigate their functions, many properties have been discussed in the literature, such as biochemical, geometrical, and mechanical properties, in both of these categories. Overall, LTE shows excellent potential in assisting hepatic disorders. However, some challenges exist that prevent the practical use of it clinically, making LTE an ongoing research subject in the scientific society.

Microtechnology-based in vitro models: Mimicking liver function and pathophysiology

“…The stiffness increases to 1–6 kPa during the progression to fibrotic liver. 128 Therefore, the effect of stiffness on liver cells in liver-on-a-chip model should be studied to mimic the pathophysiology of liver diseases.…”

Hepatic Differentiation of Stem Cells in 2D and 3D Biomaterial Systems

“…Biomaterials for modulating stem cell differentiation can be generally categorized into natural and synthetic polymers [ 44 ], and can be applied as 2D coatings or 3D scaffolds [ 45 , 46 ]. 3D scaffolds can be fabricated with conventional methods such as freeze-drying, particle leaching, and gas foam, whereas more advanced processing technologies such as 3D printing and microfluidic-based cell encapsulation have been recently developed to facilitate the control of scaffold properties (A detailed review of the fabrication technologies for tissue engineering was published elsewhere [ 47 , 48 , 49 ]).…”

Combating COVID-19 with tissue engineering: a review

“…As a result of clinical studies, it was determined that hepatocyte transplantation is less invasive than orthopic liver transplantation and can be performed safely in severe patients [154]. In hepatocyte-based studies, the encapsulation technique is generally used to increase cell viability and proliferation rate [155]. Such a system can be used for congenital liver injuries for COVID-19 patients.…”