Biomedical Engineering Reference
In-Depth Information
moduli: 0.01-1.5 kPa) support enhanced neurite extension
in vitro
while stiff hydrogels (elastic
moduli: 3 kPa) are nonadhesive for neurons [110].
As far as synthetic polymers (e.g., polyethylene glycol) are manipulated to represent stiff-
ness similar to natural biomaterials (e.g., collagen), the viability and neurite outgrowth from
dissociated embryonic chick DRG are promoted [111]. It has been shown that the mechanical
properties (e.g., yield strength) of PCL melt-electrospun microfibrous mesh were altered by
changing the fiber diameter and porosity of the scaffold to the point that NPs derived from
murine R1 ESCs could reactively survive, adhere, migrate, and differentiate into neurons on top
of these substrates after 14 days of culture [112]. By changing the rigidity of self-assembled
peptide nanofibers, the effect of substrate stiffness on morphological development of hippo-
campal neurons was investigated. In one study, the neuronal polarity of primary mouse
hippocampal neurons was accelerated on soft nanofibers, while multiple short neurites were
formed on stiff substrates (Figure 15.5) [101]. After 7 days in culture the astrocyte number
decreased tenfold on soft nanofibers compared to stiffer ones (Figure 15.6) [101].
Overall, although soft substrates promote the neuronal differentiation and neurite
extension of hippocampal neurons, other type of neurons respond better to stiffer materials
[113-115]. These investigations have shown that other ECM factors, as well as location and
time-point parameters in addition to mechanical cues may affect neuronal responses.
Role of Piezoelectric Substrates
Piezoelectric (PZ) substrates that produce oscillating electric fields serve as electro-mechanical
active materials and eliminate the need for electro-conductive polymers or wired-control
electrical fields [116-119]. Attachment of cells through focal adhesion complexes to PZ bio-
materials
in vitro
results in matrix deformation and enhanced cellular interaction in comparison
with non-PZ substrates. This phenomenon can be induced via cerebrospinal fluid motions
in vivo
[89]. A patient's own movements or transcutaneous ultrasound stimulations in the
vicinity of the implanted material can induce electrical effects [120].
Stiff PA
Non-polar
neuron
Soft PA
Figure 15.5
Schematic illustration of peptide nanofiber stiffness on neurite motility and polarity
development (arrows indicate the extension and retraction events at a given time-point) [101].
