Advancements in in vitro hepatic models: Application for drug screening and therapeutics

The liver is one of the most complex organs in the body, performing a multitude of functions. Liver tissue engineering is a combination of various strategies that aim at generating functional liver tissue that can help restore and/or support the ailing liver as it recuperates. Conventionally, in vitro culture has involved growing cells in different media compositions or layering them on matrices largely composed of native ECM components such as collagen or Matrigel. With recent advances in technology, more sophisticated techniques are being devised that are better equipped to capture distinct features of the liver in an in vivo microenvironment. Three-dimensional (3D) cultures of liver cells in 3D scaffolds, as spheroids or cell sheets, allow for a high degree of cell-cell and cell-matrix interaction and an in vivo-like architecture. More recently, decellularized matrices have been used as scaffolds that support ideal cell-matrix interactions. Microfabrication technologies initially used to pattern semiconductors in the integrated circuit industry have grown out of this field and now encompass a variety of methods to etch patterns onto both 2D and 3D scaffolds to allow incorporation of custom-made features resembling the fluid network and organization in native liver. This improvisation permits for enhanced vascularization and oxygen diffusion to the in vitro liver tissue. In this review, we discuss the various configurations that have been implemented in the in vitro culture of liver cells and their application in liver therapeutics in the form of implantable liver tissue constructs and tools for drug screening.