BLOOD VESSEL REGENERATION - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 146

inside of the blood vessel. These cells are critical for the control of hemostasis and maintaining the
patency of the blood vessel. Additionally, these cells provide a layer that is selectively permeable while
at the same time providing a lining that regulates platelet and leukocyte adhesion and aggregation, and
influences smooth muscle cell migration and proliferation. The endothelial cells in this region deposit
and maintain a basement membrane of type IV collagen and laminin. There is an elastic laminin layer
separating this layer from the next cell population. The middle layer, or tunica media, is characterized
by the presence of smooth muscle cells. These cells are organized concentrically and control vasocon-
striction and vasodilatation. The outermost layer, the tunica adventitia, is comprised primarily of fibro-
blasts. This layer's extracellular matrix is different from the other layers in that it is made up of collagen
I, elastin, laminin, and fibronectin. The exact composition of this layer and the presence of various
growth factors and cytokines greatly influence the mechanical strength and local cell response, and this
composition varies based upon location and function in the body. These three layers work in tandem to
control and modulate the physical and biological properties of the blood vessel. The recapitulation of
these three main layers is critical to the success of a tissue-engineered vascular implant, and as such,
much research has been carried out to develop manufacturing methods to address the heterogeneous
nature of human vasculature.
7.1.1 ADDITIVE MANUFACTURING
In order to manufacture mimetic scaffolds for vascular applications, 3D printing is increasingly
being employed as it provides the ability to tailor scaffolds with stringent control of the material on a
layer-by-layer basis. Additive manufacturing has been present in industrial applications, but has only
recently become an emerging technology for use in tissue engineering applications ( Horn and Har-
rysson, 2012 ; Melchels et al., 2012 ; Marga et al., 2012 ; Schubert et al., 2013 ; Derby, 2012 ; Barron
et al., 2004 ; Xu et al., 2005 ; Campbell and Weiss, 2007 ). However, other technologies exist that can
mimic the native structures and architecture with a more global approach and as such will be briefly
discussed in this chapter.
One critical aspect of the advancement of 3D printing, or rapid prototyping and additive man-
ufacturing, with regards to tissue engineering is the development of vascularized tissues. Efficient
vascularization would allow for incorporation into the host tissue as well as provide an avenue for
necessary nutrient and waste exchange. The circulatory system is how the body naturally maintains
homeostasis, transports waste and nutrients, delivers chemical signals, and provides rapid delivery of
the hosts' defenses. It is therefore especially important that any implanted tissue engineered construct
incorporates vascularization in its design.
Advances in computer-aided design have also had an impact on the rational design of tissue-engineered
implants for vascular regeneration ( Horn and Harrysson, 2012; Barron et al., 2004; Almeida Hde and
Bartolo, 2010; Guillotin et al., 2010; Hirt et al., 2014; Jakab et al., 2010 ). As mentioned previously, the
main cellular component of the inner layer of vasculature is endothelial cells. These endothelial cells
maintain homeostasis through the formation of a boundary reinforced with their cell-cell junctions and
their deposited ECM, and secrete various growth factors to control proliferation and cell recruitment,
and induce ECM production. In this regard, CAD approaches have been beneficial because they can be
used to model the shear stress that the ECs will be exposed to upon implantation in the body. It is well
known that EC protein expression is modulated by shear stress, and by controlling the microenviron-
ment that the cells are exposed to, the expression of proteins, such as platelet-derived growth factor