Hyaluronic Acid-based Scaffolds for Brain Tissue Engineering - Hyaluronic Acid for Biomedical and Pharmaceutical Applications - page 125

glycoprotein (OMgp), and Nogo, inhibit neurite outgrowth;
(5) oligodendrocyte apoptosis results in demyelination, leaving
uncovered neurons; and (6) lack of trophic or nutritional factors.
6.3 Current Tissue Engineering Strategy for Brain
Regeneration
From a tissue engineering point of view, the tissue engineering triad
of scaffold, cell, and regulators are all quite critical for restoring or
regenerating damaged tissues. The new generation of tissue engineered
scaffold is not just a simple framework, but could participate in the
regulation of tissue generation, serving as an artificial ECM to regulate
cell attachment, proliferation, migration, differentiation and neotissue
formation [19]. Considering the complexities of brain tissues and the
growth inhibitory environment formed following injury, biomaterials
used in brain tissue should have appropriate degradation rates, as
well as allow infiltration of cells and axons, and transportation of
nutrients and metabolites. Ideally, biomaterial scaffolds should have
sufficient bioactivities to recruit endogenous cells and growth factors
to help tissue regeneration, and also induce axon re-growth and re-
connection of synapses. Therefore, when designing a novel scaffold,
material and biological parameters, such as the effect of the modulus
of elasticity [20], architectural structures [21] and modification with
ECM components [22] should be taken into consideration. In recent
years, a wide range of biomaterials including collagen, HA, chitosan,
poly(lactic- co -glycolic) acid (PLGA), polyethylene glycol, and self-
assembling peptides have been applied in brain tissue engineering
[23-29]. In addition, scaffolds can also be modified for controlled
drug delivery, e.g., the release of myelin derived inhibitors such as
Nogo, MAG and OMgp to reduce astrocyte scarring around the
defect, and neurotrophic factors (nerve growth factor, brain-derived
neurotrophic factor (BDNF) and glial derived neurotrophic factor
and so on) to stimulate neurite ingrowth into the defect [30]. At the
same time, exogenous cells, especially stem cells, are thought to be
necessary because of limited amplification of endogenous cells in the
adult brain [29]. Cell-scaffold complexes are being therefore widely