Cell patterning for liver tissue engineering via dielectrophoretic mechanisms

Abstract

Liver transplantation is the most common treatment for patients with end-stage liver failure. However, liver transplantation is greatly limited by a shortage of donors. Liver tissue engineering may offer an alternative by providing an implantable engineered liver. Currently, diverse types of engineering approaches for in vitro liver cell culture are available, including scaffold-based methods, microfluidic platforms, and micropatterning techniques. Active cell patterning via dielectrophoretic (DEP) force showed some advantages over other methods, including high speed, ease of handling, high precision and being label-free. This article summarizes liver function and regenerative mechanisms for better understanding in developing engineered liver. We then review recent advances in liver tissue engineering techniques and focus on DEP-based cell patterning, including microelectrode design and patterning configuration.

Figure 1.

A broad outline of important events in liver generation. Reproduced from [16] with permission.

Figure 2.

(a) SEM image of ALG/GC scaffold for hepatocytes attachment [23]. (b) Cell sheet technology for passive cell patterning using PIPAAm-grafted surface [24]. (c) Microfluidic 3D hepatocyte chip utilizing micro-pillars for cell culture [25]. (d) Perfused multi-well plate with an array of 12 scaffold-based bioreactors [26]. (e) Soft lithography to fabricate hepatocytes micropatterning in a multiwell format [27]. (f) Microelectrode for active liver cell patterning via DEP mechanism [28]. Reproduced with permission.

Figure 3.

Principle of dielectrophoresis in an inhomogeneous electric field. Cells that are more polarizable than the surrounding medium are attracted towards the high electric field at the smaller electrode.

Figure 4.

Concentric-stellate-tip microelectrode for 2D liver cell patterning. Reproduced with permission [74].

Figure 5.

(a) Vertical setup for 3D heterogeneous cells patterning by DEP. (b) The lobule-mimetic-stellate-electrode arrays for 3D liver cell patterning. Reproduced with permission [28].