Exploring Potential of Silk 3D Matrices for Bioartificial Liver and Regenerative Applications

Abstract

Advanced liver cirrhotic patients are limited with liver transplants as the only therapeutic option; indeed, the practical applications of liver transplantation possess several drawbacks. The criteria for engineering 3D hepatic constructs for liver regenerative medicine are (i) cell-cell and cell-matrix interactions assisting long-term cell viability, (ii) heterotypic culture of liver cells maintaining cell functionality, (iii) long-term liver-specific synthetic, metabolic, and detoxification functions, and (iv) facilitating the regeneration of damaged tissue. A suitable 3D matrix with appropriate biocompatibility, hemocompatibility, topography, and physicochemical attributes facilitates hepatocyte aggregation, polarity, differentiation, and proliferation. Herein, mulberry Bombyx mori (BM) silk fibroin, non-mulberry Antheraea assamensis (AA) silk fibroin, and decellularized liver extracellular matrix (ECM) are explored in the domain of liver tissue engineering owing to their biochemical composition, mechanical stiffness, biocompatibility, and biodegradability. The presence of intrinsic RGD (arginine-glycine-aspartic acid) motifs and the high mechanical strength of AA silk fibroin has made it a potential biomaterial as it enhances cellular attachment and cell-matrix interactions. The prominent role of LECM hydrogel in liver tissue engineering has been emerging, owing to the presence of growth factors, cytokines, and cell-secreted exosomes.