Tissue engineering for the nervous system

Tissue engineering for the brain emerged as a promising therapy for traumatic brain injuries (TBIs) after the discovery of neural stem cells (NSCs) in the subventricular zone (SVZ) and the subgranular zone (SGZ). Combining NSCs with novel bioactive scaffolds may encourage and direct tissue regeneration and ultimately repair tissue damaged due to injuries. In this thesis, a number of collagen-based scaffolds were fabricated into an interlaced network structure. The scaffolds comprised collagen (Coll), hyaluronic acids (HA) and chondroitin sulfates (CS), where the latter two are commonly-found glycosaminoglycans (GAGs) in the brain’s extracellular matrix (ECM). Our novel tri-interlaced network scaffold, Coll-CS-HA, is the first to be constructed, characterized and tested on NSCs. The synthesis method successfully incorporated HA and/or CS into the interlaced scaffolds, as demonstrated by FTIR, EDX and histology. Compressive testing and SEM also showed that the interlaced scaffolds had consistent and adequate mechanical properties and pore structure suitable for NSC growth. Further cell biology studies demonstrated excellent biocompatibility of all scaffolds as evidenced by high cell survival. Interlaced scaffolds encouraged higher cell differentiation, shown by a halved nestin expression, a marker for NSCs, compared to Coll. An increase in MAP2 expression, a marker for mature neurons, by 50-100% in proliferation and differentiation was also observed. Coll-CS scaffolds led to an increase in astrocytic differentiation shown by a doubled GFAP expression, which has been related to glial scar formation. As a result, Coll-HA and Coll-CS-HA may hold therapeutic potential to become candidates for future TBI treatments as they combined the advantage of adequate mechanical properties similar to that of brains, a high neuronal differentiation of around 40%, and a low astrocytic differentiation of around 20%.