Biomedical Engineering Reference
In-Depth Information
which leads to gene expressions different from unstretched cells. Increasing metabolic
activity and proliferation rates were seen for cells on hybrid matrices. When the diameter of
the fibers is lower than the cells, they can adhere well around the fibers and organize them-
selves. In addition, filling large spaces of the microfiber meshes with nanofibers will result
in higher cell-seeding efficiency because more cells could be retained inside the
structure [61].
Self-assembled Peptides
Self-assembly is to fabricate nanofibers through weak noncovalent interactions from small
molecules, proteins, peptides, and nucleic acids [15]. Several peptides such as short fibrilliz-
ing peptides, β-hairpins, peptide-amphiphiles, and peptide derivatives self-assemble to form
networks of β-sheet-rich nanofibers, which further merge to build supramolecular hydrogel
architectures for tissue engineering application.
For example, the peptide RADA16-I (AcN-RADARADARADARADA-CONH2),
which is an alternating 16-residue peptide with basic arginine, hydrophobic alanine, and
aspartic acid, can undergo spontaneous assembly into well-ordered interwoven nanofibers
in water and rapidly form hydrogels with ~10 nm fiber diameter, 5-200 nm pore size
and > 99% water content under physiological conditions, which is similar to the structure
of natural ECM. This mild cross-linking chemistry allows yielding viable encapsulated
cells for three-dimensional culture. This self-assembled peptide and its several different
functional motifs with other short peptide sequences have been used as a well-defined microenvi-
ronment for stem cells. Mouse ESCs encapsulated in RAD16 showed undifferentiated stem-cell
maintenance [62]. Functioning peptide mixtures RAD/SKP (Ac-(RADA)4GGSKPPGTSS-
CONH2), RAD/FHR (Ac-(RADA)4GGFHRRIKA-CONH2) and RAD/PRGD (Ac-(RADA)
4GPRGDSGYRGDS-CONH2) onto three-dimensional matrices have been demonstrated to
control human adipose stem cell (hASC) behaviors
in vitro
[63]. Modified RADA16 with bone
marrow homing peptides (BMHPs) has also been successfully applied to NSCs [64].
Multidomain peptides (MDPs) are a type of amphiphilic self-assembling peptides with a
modular ABA block design in which the amphiphilic B block drives self-assembly while the
side A blocks, which are electrostatically charged, control the conditions of assembly
procedure. Galler
et al
. synthesized a range of multidomain peptides for fabricating nanofi-
bers. The peptides were modified with enzymatic cleavage and a supplement of cell adhesion
motifs (RGD). Combination of these items led to an increase in MSC viability and prolifer-
ation and encouraged cell migration within the matrix [65].
Peptide-amphiphiles (PAs) are oligo-peptides including a hydrophobic N-terminal alkyl
tail, a β-sheet-forming segment in the middle, and a hydrophilic C-terminal functional seg-
ment for increasing cell adhesion [20]. These molecules generally self-assemble into high-
aspect-ratio rods/cylinders with a hydrophobic core and a hydrophilic region on the exterior
of the fiber for cell interaction. The exterior region can be tailored to provoke desired
chemical and biological responses, such as cell adhesive ligands and cell-mediated degrad-
able sites to control cellular behaviors [66]. Mesenchymal stem cells [67-69] and NSCs [66]
have been incorporated into the PA nanofibers for proliferation and differentiation.
Nanocomposites
Although nanofibers have gained wide application to support attachment and proliferation
of stem cells, a macroporous structure and weak mechanical properties are key limiting
factors for specific tissue regeneration. The nanofibers can be blended with nanoparticles,
