Abstract:

Traumatic injuries to the central nervous system trigger a series of secondary biochemical and cellular responses that ultimately lead to cellular death and maintenance of an unsupportive extracellular matrix (ECM) for tissue regeneration. Artificial ECM or scaffolds represent a way to alter this unsupportive environment to improve the efficacy of stem cell therapies and enhance neural tissue regeneration. The inclusion of basic scaffolds with stem cell therapy treatments have shown increased efficacy in rodent models. More advanced scaffolds could better mimic the chemical, physical and mechanical properties of the ECM to promote survival, adhesion, proliferation and differentiation altering the injured ECM to mitigate the barriers to axon invasion, myelination and cellular maturation. Changes in IKVAV concentration have been implicated in altering cellular attachment and neural differentiation. In 2D culture, maximal neurite extension and neural gene expression occurred on hydrogels. While in 3D culture, neurite extension was delayed. The common thread to many of the changes between 2D and 3D culture is a real or perceived change in the concentration of elements (cytokines, tethered bioactive signaling, etc.) by the cell in its extracellular milieu. The complexity of how the concentration changes interact with cells to change cellular survival, attachment, and differentiation throughout central nervous system development is not yet well understood. Unraveling the effects of these concentration changes will ultimately lead to a better understanding of tissue development allowing us to begin to effectively manipulate the extracellular environment with scaffolds, drugs, stem cells, etc. to restore neurological function after traumatic brain and spinal cord injuries.