Tissue engineering of organs: Brain tissues

Abstract

Brain tissue engineering (BTE) involves the application of a combination of replacement cells, synthetic scaffolds, and biomolecules to restore and repair damaged neuronal pathways. This strategy is of particular biological importance because of the limited capacity for self-repair in the brain following disease and/or injury, and the severe impact on the quality of life of affected patients. In BTE approaches that are on the basis of the use of scaffolds, neuronal repair must be preceded by an ability of the implanted scaffold to integrate with the host brain tissue, suppress the extent of inflammation at the injury site, and to provide a permissive and instructive environment for neuronal regeneration. Most scaffold design strategies attempt to simulate the molecular and structural features of the native extracellular microenvironment that facilitate neuronal regeneration. Currently, the ability to engineer these types of scaffolds down to the nano-scale enables a much greater degree of biomimicry of tissue architecture. This in turn promises to provide finer control over cell-scaffold interactions, and subsequent cell behavior including contact-mediated migration and neuronal differentiation. The ideal BTE scaffold must have appropriate porosity and three-dimensional (3D) architecture to permit cell infiltration and proliferation, as well as to provide a physical platform to maintain the intrinsic tissue architecture. Such scaffolds can be further functionalized with bioactive extracellular matrix molecules or signaling proteins to influence cell behavior. In addition, scaffolds can provide a means of encapsulating exogenous neuronal support cells for delivery to local injury sites to encourage regeneration. The extensive research toward understanding and optimizing bio-engineered scaffolds for neuronal regeneration applications promises to lead to more prominent therapeutic approaches for various brain diseases and injuries. Despite the many hurdles that remain in translating promising in vitro and in vivo results into functional recovery in clinically relevant models of brain disease and injury, it is anticipated that BTE will provide a more targeted treatment approach for efficient recovery with fewer side effects, an alternative to currently available treatment modalities.