Biomedical Engineering Reference
In-Depth Information
biochemical traits. However, the precise role of natural matrices in this regard remains an
oddity since they may induce immunological and inflammatory responses due to the presence
of undefined components. On the contrary, synthetic biomaterials possess advantages in
manufacturability and lower lot-to-lot variability, which permit us to more easily and pre-
cisely adjust key parameters of substrates such as architecture, stiffness, and electrical
properties. Biofunctional cues can be added to the synthetic scaffolds to overcome their
poor biocompatibility and lack of recognition signals. The role for this type of scaffold will
be further discussed later in the 'Biophysical' section.
Role of Growth Factors, Signals, and Bioactive Molecules
Protein Incorporation for Improving Cell Function
Spatio-temporal cues such as growth factors, mitogens, neurotrophic factors, and morphogenes
are biomolecules that are actively involved in the regulation of neural development, survival and
function, and progenitor differentiation [28, 29]. In order to promote cell function, artificial
biomaterials can be modified with several types of these bioactive molecules. Presentation
of bioactive molecules to biological substrates also allows for the study of cellular internalization
dynamics and roles of specific signal-transducing ligands in neural cell-fate decisions. Through
introducing the bioactive factors to biomaterials, besides the enhancement of attachment,
proliferation, and differentiation of transplanted cell, endogenous NSCs can be induced to pro-
liferate and differentiate at the legion sites [20]. Such being the case, developing bioactive scaffolds
with proper chemical properties can increase the value of neural tissue engineering in terms of
regenerative medicine. The roles of neural master growth factors in this matter will be discussed.
Growth Factors
During development, growth factors, or soluble-secreted polypeptides, can use their signal
transduction ability to instruct cell behavior by binding to specific cell-surface receptors and
trigger changes in the cytoskeleton, metabolism, gene expression, and protein synthesis.
These changes result in specific cellular responses [30]. In order to properly affect cellular
target receptors by diffusion, the soluble growth factors must be present for long periods of
time. As the half-life of growth factors is short, the efficacy of delivery can be boosted
through their incorporation within the bioengineered three-dimensional scaffolds [31].
However, undesired levels of delivered growth factor can lead to numerous side-effects due
to overextension of neural projections beyond their specific targets, which are implicated in
progressive neuronal death [32]. Adding growth factors into the scaffolds allows for control of
their multiple functions, enables the desired delivery, and simultaneously presents multiple cues
to make them highly favorable for neural-tissue regeneration. Protection against proteolysis in
local protein-delivery systems can be achieved by their incorporation into materials such as
heparin and increase the duration of their activity [33]. Immobilized bioactive molecules have
enhanced biological activities compared to their soluble forms and can assist neuronal cell
survival, proliferation, differentiation, and fate modification
in vitro
and
in vivo
[34]. For
example, membrane proteins such as notch ligands or delta that are not activated by soluble
ligands, can be immobilized for improved activities
in vitro
[35].
The most commonly used growth factors for neural cells are nerve growth factor (NGF),
brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF),
ciliary neurotrophic factor (CTNF), insulin-like growth factors (IGFs), epidermal growth
factor (EGF), and fibroblast growth factors (FGFs).
