Abstract
Progress is being made in developing neuroprotective strategies for traumatic brain injuries; however, there will never be a therapy that will fully preserve neurons that are injured from moderate to severe head injuries. Therefore, to restore neurological function, regenerative strategies will be required. Given the limited regenerative capacity of the resident neural precursors of the CNS, many investigators have evaluated the regenerative potential of transplanted precursors. Unfortunately, these precursors do not thrive when engrafted without a biomaterial scaffold. In this article we review the types of natural and synthetic materials that are being used in brain tissue engineering applications for traumatic brain injury and stroke. We also analyze modifications of the scaffolds including immobilizing drugs, growth factors and extracellular matrix molecules to improve CNS regeneration and functional recovery. We conclude with a discussion of some of the challenges that remain to be solved towards repairing and regenerating the brain.
Highlights
Tissue engineering (TE) is a relatively new and expanding field
Arvidsson et al [20] researched the mechanisms of neuronal repair after stroke in an adult rat model and reported that less than 1% of the destroyed neurons are replaced from the endogenous neural precursors (NPs) of the subventricular zone (SVZ)
We have shown that fetal rat NPs plated onto a multifunctional film comprised as described above proliferated and remained multipotent for at least 3 days without providing soluble fibroblast growth factor-2 (FGF-2)
Summary
Tissue engineering (TE) is a relatively new and expanding field. Using principles from material engineering and molecular biology, tissue engineers develop organic substitutes to support or replace portions of malfunctioning tissues or organs [1]. Macrophages clear away the remnants of dead or dying cells, but the injury creates a harsh, non-permissive environment that lacks nutrients, survival factors and most importantly, a habitable substrate and the extracellular matrix (ECM) that they once resided within [14,39,40,90] This ECM is a scaffold that provides cells with structural and functional support. Natural biomaterials Tate and Shear, were some of the first investigators to use stem cells for brain TE in models of TBI They produced collagen gels that contained either fibronectin and/or laminin and showed that these scaffolds increased the survival of transplanted mouse NPs compared to NPs transplanted without the collagen matrix. Mouse NPs E14 Rat NPs Adult hippocampal NPs Human NPs derived from ESC line C17.2 cell line, ReNcells, and GRPs Rat NPs
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