NANOTECHNOLOGY: A TOOLKIT FOR CELL BEHAVIOR - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 11

scaffolds with considerably improved mechanical and biochemical properties is of great prominence.
In ligament tissue engineering, the fibrous nature of the natural tissue has inspired researchers to use
electrospun scaffolds with a density gradient, similar to the nHA constituent in osteochondral tissue
engineering, generating a stiffness gradient along with a multimaterial approach ( Kuo et al . , 2010 ; Sa-
mavedi et al . , 2011 ). This multiphasic approach consisted of co-spinning PCL with incorporated nano
hydroxyapatite and poly(ester urethane). The result was a graded scaffold that had both a biochemical
gradient and a mechanical strength gradient that more accurately mimicked the natural ligament ECM
( Samavedi et al . , 2011 ).
1.3 3D NANO/MICROFABRICATION TECHNOLOGY FOR TISSUE
REGENERATION
1.3.1 3D NANOFIBROUS AND NANOPOROUS SCAFFOLDS FOR TISSUE
REGENERATION
1.3.1.1 Electrospun Nanofibrous Scaffolds for Tissue Regeneration
The most prominent nanofibrous scaffold fabrication method is electrospinning. Similar to the afore-
mentioned electrospraying technique, electrospinning utilizes the same equipment, but with a polymer
of higher viscosity, allowing the stream not to break up and form droplets. It is a process by which a
charged polymer is dissolved in solvent, and exposed to a large voltage potential of several kilovolts as
it is slowly pumped from a needle. The large electrical potential causes the fluid to be drawn out into
a fine stream which solidifies into fibers that can be dimensionally controlled by varying the viscos-
ity, voltage potential, flow rate, and working distance between the needle and collector plate during
fabrication. Figure 1.5 A shows an electrospun highly aligned fibrous scaffold with conductive CNTs
fabricated in our lab. This type of nanofibrous scaffold tends to be most effective when used for tissues
with similar fibrous morphologies, and have been shown to be effective in many skin, musculoskeletal,
and neural tissue regeneration applications ( Holmes et al . , 2012 ; Zhu et al . , 2014a ). Popularity for
neural tissue engineering is due to the ability to create highly aligned nanofibrous scaffolds from many
biocompatible polymeric materials. These scaffolds have been shown to more effectively promote
neural outgrowth to bridge given defect sites ( Assmann et al . , 2010 ).
Even though electrospinning normally creates thin constructs, the high surface area to volume ratio,
nanometer feature size, and relative ease of fabrication make electrospun nanofibrous scaffolds benefi-
cial for bone and cartilage tissue engineering, which have been thoroughly reviewed in our previous
paper ( Holmes et al . , 2012 ). For example, Aclam et al . used electrospun PCL nanofibers and collagen
type I to create an injectable scaffold that promotes bone regeneration. Briefly, they electrospun PCL
fibers, combined them with a cell-laden collagen gel, and allowed the composite to crosslink naturally
at physiologic conditions. After 21 days of culture, the injectable scaffolds showed increased total
protein, alkaline phosphatase, and calcium concentration when compared to a pure collagen control
( Baylan et al . , 2013 ).
1.3.1.2 Other 3D Nanofibrous/Nanoporous Scaffolds for Tissue Regeneration
Besides nanofibrous scaffolds fabricated via electrospinning, other fabrication methods for nanofibrous
or nanoporous scaffolds are also commonly utilized in tissue engineering. For instance, for musculo-
skeletal tissue studies, conventional scaffold fabrication methods such as solvent casting and particle