Figure 5.

Requirements for the successful redirection of endogenous neuronal stem cells with biomaterial and tissue-engineered scaffolds. (A) Schematic depicting a nondescript tissue-engineered scaffold implanted into a gyrencephalic brain spanning from the SVZ to a region of injury. In order for scaffolds to successfully re-direct endogenous NPCs, there (B) must be a sufficient quantity of NPCs in the SVZ, (C) neuroblasts must migrate long distances within the scaffold, and (D) biomaterials composing the scaffolds should not elicit a detrimental immunogenic foreign body response from local and/or recruited glial cells surrounding the implant. Redirected NPCs must (E) differentiate into appropriate phenotypes, (F) arrange into appropriate architecture, and (G) integrate into existing circuitry once they reach their new destination within the brain. Scaffolds may need to be adapted to promote maturation into multiple neuronal phenotypes if differentiation cues at destination are insufficient. Consideration must also be given to how a diseased environment may affect the health of the redirected NPCs. Long-term biocompatibility of the scaffolds with surrounding brain tissue, appropriate degradation rate, and optimal time window for implantation must also be considered. Original figure created by Dayo Adewole, Department of Bioengineering, University of Pennsylvania.