DESIGNING NANOFIBROUS SCAFFOLDS FOR TISSUE ENGINEERING - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 435

[44], solvent casting and particulate leaching [45], membrane lamination [46],
melt molding [47], in - situ polymerization [48] , freeze drying [49] , gas - foaming
processing [50], extrusion [51], 3D printing [52] and polymer foams [53] are some
of the techniques that have been explored for the synthesis of a porous 3D scaf-
fold. As stated earlier, ECM is composed of nanoscale components that provide
structure as well as guidance to cells. Thus, tissue engineers desire to develop
nanofi ber-based scaffolds that would essentially mimic the native ECM and
favor the cell fate processes in the direction of tissue development/regeneration.
Fibrous scaffolds have been synthesized by three methods, namely: self assembly,
phase separation, and electrospinning. These three methods offer nanoscale
dimensions in fi brous form along with the architecture that have potential to be
used as an artifi cial ECM [54].
This section will briefl y describe self assembly and phase separation tech-
niques and will focus on electrospinning and its applications in tissue engineering.
13.3.1 Self Assembly
Also known as self organization, self assembly is the reversible process of forma-
tion of structured patterns from components of a pre-existing system that are not
associated with structure/order [55]. The native ECM or the cellular microenvi-
ronment not only provides physical support but also provides ligands for cell
attachment thereby facilitating cell fate processes such as cell adhesion, migration
and differentiation [36]. Self assembly can be used to create scaffolds with well-
defi ned 3D architecture at the nanometer scale to facilitate cell adhesion, conse-
quential function and hence tissue regeneration [56]. Self assembly has been
reported in multiple natural processes, such as during nucleic acid synthesis and
protein synthesis, with these assembles mostly being governed by non-covalent
interactions, such as ionic, Van der Waals, and hydrophobic interactions, as well as
hydrogen bonds [57]. Taking cues from these natural processes, Hartgerink et al.
reported the self assembly of peptide-amphiphiles [PA] for the formation of
nanofi bers. They demonstrated the mineralization of hydroxyapatite directed by
self - assembled collagen fi bers, thereby mimicking the hierarchical structure of
bone. In their studies, the alkyl chain length and peptide amino acid composition
was varied to allow for the synthesis of nanofi bers with varying morphology,
surface chemistry and bioactivity [58,59] (Figure 13.2). Further, Hosseinkhani
et al. reported the synthesis of hepatocyte growth factor (HGF)-loaded, self-
assembled PA nanofi bers. Their results demonstrated enhanced vascularization in
mice models following the subcutaneous injection of PA along with HGF, which
was due to sustained release of the growth factor, as compared to the positive
control (HGF only) [60] .
An advantage associated with the process of self assembly is that it can be
performed under physiological conditions without the usage of any harmful
organic solvents, thereby making the technique more amicable for in vivo appli-
cations. Despite the ability to synthesize fi bers having diameters in the nanometer
scale, the process of self assembly remains a relatively complicated process and is