The reproducibility of CIVMs is hindered by the batch-to-batch variability of animal-derived scaffolds, such as the numerous observations of inconsistencies between batches of Matrigel. For example, numerous growth factors, chemokines and biologically active proteins have been detected by proteome array in Matrigel that may have significant implications on cellular behaviour when cells are grown in or on the matrix. The inclusion of animal-derived scaffolds in CIVMs limits their physiological relevance. Materials used as scaffolds for 3D cell cultures are often derived from animal cells, such as Matrigel, or directly extracted from animal tissue, such as rat tail collagen. ĬIVMs have diverse applications in research and regulatory testing and are a key technology in moving towards increasingly human-relevant models. ![]() Thus, the development of vascular-like scaffold structures, the formation of functional bile ducts, and the maintenance of complex metabolic functions remain as major problems in hepatic tissue engineering and will need to be addressed to enable further advances toward clinical applications.The development of organoids, organotypics, micro-physiological systems and other 3D culture techniques allow the recapitulation of complex physiological tissues and organs in vitro. These complex in vitro models (CIVMs) facilitate the study of specific mechanisms or pathways using human tissue or cells in a more physiologically relevant environment than traditional 2D culture methods. The major limitation of cells proliferated with matrix-based transplantation systems is the high initial cell loss and dysfunction, which may be due to the absence of blood flow and the changes in nutrients. In addition, a system for growing stem cells, liver progenitor cells, and primary hepatocytes for transplantation into animal models was developed, which produces hepatic lineage cells that are functional and that show long-term proliferation following transplantation. Furthermore, beneficial effects of addition of growth factor cocktails to a flow bioreactor or coculture system on cell viability and function have been observed. In cultures of hepatic lineage cells, regulation of cell proliferation and specific function using biocompatible synthetic, biodegradable bioderived matrices, protein-coated materials, surface-modified nanofibers, and decellularized biomatrix has been demonstrated. Moreover, the scaffold plays a role in regulating cell maturation and function via these interactions. Particular materials or a matrix serve as a scaffold and provide a three-dimensional environment for cell proliferation and interaction. Tissue engineering aims to mimic the interactions among cells with a scaffold. Therefore, liver tissue engineering based on cell transplantation that combines materials to mimic the liver is under investigation with the goal of restoring normal liver functions. ![]() However, one main problem with liver transplantation is the limited number of donor organs that are available. Liver transplantation is currently the most efficacious treatment for end-stage liver diseases.
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