BLOOD VESSEL REGENERATION - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 149

This provides a unique set of environmental conditions that are continually changing, and as a result,
any implant must be able to survive this range of conditions.
To address the clinical need for biocompatible and biodegradable vascular grafts, tissue-engineering
approaches have become more widely utilized to improve vascular regeneration. These approaches are
varied in the methods used to generate the grafts or scaffolds to promote vascularization and angio-
genesis, but the main concepts behind the design of the grafts remain largely the same. The common
features can be broken down into the components of the implant: (1) the scaffold, (2) functionalization,
and (3) cells necessary for vascular regeneration. Some of the methods used by the tissue engineering
community to fabricate these therapeutic implants are electrospinning, molding, and rapid prototyping
of cell-free scaffolds and cell-based printed scaffolds. A selection of these methods, currently em-
ployed in scientific literature, will be discussed in the following sections with an emphasis on 3D
printing technologies.
In the manufacture of these implants, there are currently two main approaches, consisting either
of a cell-free or a cell-based system of designing and creating the implants for vascular regeneration.
These two approaches can be broken down further into the underlying technologies that allow for
the creation of these tissue-engineered implants. The cell-free scaffolds are typically created using
technologies such as electrospinning, chemical vapor deposition, and 3D printing. These methods are
discussed in more depth in the next section. Cell-based implants for vascular regeneration are produced
either through the seeding of the cell-free scaffolds prior to implantation or through the direct creation
of scaffolds where the cells are embedded in the scaffold during the production. The production of
these cell- laden constructs is discussed in depth in Section 7.6.1 and focuses primarily on current and
emerging technologies for 3D printing cells for vascular regeneration applications.
7.1.3.1 Cell-Free Scaffolds
Investigations into blood vessel regeneration and growth have focused on the use of cell-free systems.
In these tissue engineering endeavors many technologies have been utilized to develop scaffolds that
encourage the growth of native vasculature either in vitro or in vivo. Generally, these technologies aim
to generate scaffolds that mimic the native vasculature and can be functionally modified as discussed
previously to develop more bioactive scaffolds. This section aims to give an in-depth discussion of how
the technologies work to generate the scaffolds and a few specific examples of how these methods are
used in literature. Due to the number of methods available, this section will discuss the following for
generating scaffolds: electrospinning, stereolithography, and fused deposition modeling.
7.1.4 ELECTROSPINNING
This topic focuses primarily on 3D printing and its application to various tissue engineering endeavors;
however, the discussion on blood vessel regeneration would not be complete without a brief discussion
on electrospinning. Nanofibrous electrospun grafts have been widely utilized for vascular regeneration
applications. The electrospinning process allows for the control of graft parameters in real time during
the fabrication process, which is precisely why electrospun scaffolds have been investigated for mul-
tiple tissue engineering applications that are not limited to the vascular system ( Fridrikh et al., 2003 ).
There are a wide number of polymers and materials suitable for this fabrication process and the costs
associated with this technology are relatively low. As a result of these two considerations, multiple stud-
ies have been carried out on a wide array of electrospun vascular grafts/scaffolds for tissue regeneration