Conclusions and Novel Trends in Liver Tissue Engineering

Until now, the development of liver tissue engineering has focused primarily on generating functional liver constructs for in-vivo use (replacement of diseased liver), or on the engineering of bioartificial hybrid BAL systems for detoxification. Novel types of scaffold that have been designed more recently for hepatic constructs, are well suited not only for implantation but also as matrices for engineering liver tissue-equivalents for basic and applied research, including in-vitro models for drug discovery and testing (e.g., for developing hepatic vaccines).

The liver is a complex organ that harbors many types ofcell; therefore, more than one cell type is required to develop a truly liver-like engineered tissue. More effort is required to provide a better understanding of the underlying molecular physiology, specifically the differentiative and functional role of cell-cell communication in liver development, as well as the cell-biomaterial interactions if we desire to engineer functional liver tissue constructs for implantation and/or for in-vitro drug discovery. This goal can be facilitated by creating complex scaffolds composed of more than one material, assuming that each material will provide support for the different types of liver cells. In order to optimize cell-biomaterials interactions, such as adhesion, migration, proliferation and differentiation of the liver cells on the scaffolds, the matrix must be able to release growth factors in a temporal and spatial gradient-controlled fashion; this will then provide the necessary inductive and differentiative environment for the different types of hepatic cells in a given construct. Continual and controlled release of the growth factors may be necessary for creating durable tissue constructs in vitro, in which case these constructs will allow drug testing for extended periods of time, similar to in-vivo experiments. We believe that in the future, liver tissue engineering will include, among others, novel platform technologies, such microelectromechanical systems (MEMS) for engineering highly vascularized liver constructs [84], micro-patterned surfaces for the co-culture of hepatocytes and Kupffer cells [87], and integrated hepatocyte spheroid constructs using electrospun nanofibrous scaffolds [88]. The challenges and potential for liver tissue engineering are vast, and some of the present achievements have provided great encouragement to continue the quest.

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