Biomedical Engineering Reference
In-Depth Information
The five steps of the TIPS method are poly-
mer dissolution, phase separation and gelation,
solvent extraction, freezing, and lyophilization.
Polymer dissolution simply involves mixing the
polymer, synthetic or natural, with a suitable
solvent. The temperature of the solution is sub-
sequently lowered by freezing the polymer solu-
tion. At these lower temperatures, the solution
becomes thermodynamically unstable, leading
to a spontaneous separation of phases. The
mostly solvent phase is evaporated through lyo-
philization (freeze drying) and, if optimal pro-
cess parameters are used, the mostly polymeric
phase forms a nanofibrous matrix with fibers
ranging in diameter between 50 and 500 nm
[43]
.
The ability to produce fiber distributions in this
range make this technique particularly utile in
tissue engineering, as the Type I collagen fibers
of the ECM have diameters in this range
[43]
.
The resulting nanofibrous shape is controlled
by fabrication parameters such as gelation tem-
perature and polymer concentration of the solu-
tion
[12]
. In addition, this process can also be
combined with a particle-leaching step to easily
create macropores in the construct.
There are, however, limitations to the TIPS
method. The sensitivity of this technique to pro-
cess variations makes it difficult to reproduce
scaffolds. Moreover, the solvent used for phase
separation is often difficult to completely remove
from the scaffold. As a result, the scaffolds could
have grave unintended consequences as a tissue
engineering product
[118]
.
of biomedical applications. In addition, the
amphipathic (having hydrophilic and hydro-
phobic qualities) molecules can be tailored to
elicit multiple biological responses after implan-
tation, a property central to optimizing regen-
erative strategies.
The chemical mechanisms of peptide self-
assembly are highly specific in that molecular
recognition mediates hydrogen bonding, ionic,
electrostatic, hydrophobic, and van der Waals
interactions
[63]
. Therefore, amino acids can be
engineered so that certain secondary structures
(
β
-sheets,
β
-hairpins, and
α
-helices) can opti-
mally interact and give rise to nanofibrils and
3D nanofibrous networks. The self-assembly
process has been shown to produce nanofibers
with diameters well below 1,000 nm, with a
distribution of 5-25 nm
[64]
.
One common method of self-assembly is to
first synthesize an amino-acid sequence and
then chemically attach an alkyl chain to the oli-
gopeptide, a peptide chain of 2-20 amino acids
in length. The oligopeptide can serve a dual
function in that it is hydrophilic, and the oligo-
peptide can be synthesized to mimic part of a
native protein of interest. The hydrophilic oligo-
peptide covalently linked to an alkyl chain
causes the molecules to assemble into nanofi-
brous geometry when the proper conditions are
applied. The specific amino-acid sequences are
often derived from common ECM proteins such
as laminin, mimicking the peptide sequences
that interact with cell receptors of progenitor
cells and promote their differentiation to the
desired cell
[65]
. Attaching an oligopeptide
domain is preferred over incorporating the entire
peptidic chain due to the ease in synthesizing
oligopeptides, stability of the shorter sequences,
and their demonstrated bioactivity
[65]
.
When the amphiphile, a surfactant molecule,
is placed under aqueous conditions, the alkyl
chain packs into the center, and the peptide
domain is exposed to the aqueous environment.
It has been well documented in the literature
that a 16-carbon alkyl chain length is optimal for
7.2.2.3 Self-Assembly
Self-assembly
involves the autonomous aggrega-
tion of molecules into thermodynamically
favored nanostructures through non-covalent
interactions. Peptidic molecules are most com-
monly used for self-assembled nanofibers as a
result of the multiple arrays of amino acids that
can be generated. Due to substantive diversity
in peptide creation, self-assembly is a suitable
technique to produce fibers with physical and
chemical properties suitable for a host
