Biomedical Engineering Reference
In-Depth Information
limit has been reported to be approximately 100-200 µm, which is
also dependent on tissue type [1]. To fabricate tissue beyond this
diffusion limit microcapillaries are required for functional tissue. The
heart, in particular, is cell dense and composed of multilayer tissue,
requiring a large amount of oxygen and nutrition, including fatty
acids and glucose, to pump blood throughout the body. In fact, the
intercapillary distance in the heart is less than 25 µm—very narrow
compared to the distance in other tissues [2]. Several papers have
demonstrated that the diffusion limit of engineered cardiac tissues
is approximately 50-100 µm; and in cardiac cell sheets the thickness
limitation without blood vessels is approximately 80 µm using
a triple-layer sheet [3]. Therefore, the vascularization limitation
is more critical for myocardial tissue engineering than for other
tissues, and researchers continue to apply advanced technologies to
engineer thicker, functional myocardial tissues.
6c.2
Biology of Blood Vessel Formation
Before we can consider blood vessel fabrication in engineered
myocardial tissue, we first have to understand in vivo blood vessel
development. There are two types of vascular development. The
first is “vasculogenesis,” which is de novo blood vessel formation
from endothelial precursors, hemangioblasts, and endothelial
progenitor cells (EPCs) [4]. The second is “angiogenesis,” which is
branch formation from existing blood vessels [5]. In vasculogenesis,
hemangioblasts differentiate into endothelial cells and form a
primitive vascular structure, which is a network of capillaries. At this
early stage, basic fibroblast growth factor (bFGF) [6] and vascular
endothelial growth factor (VEGF) [7] are important factors for their
development, after which these structures become mature vessels.
Angiopoietin-1 and Tie-2 signal transduction is necessary for the
maturation step of recruitment and interaction of supporting cells
“pericytes” [8]. Recently, EPCs have been studied as a potential
source of endothelial cells because they can be harvested from
peripheral blood and differentiate into endothelial cells as well as
hemangioblasts [9]. Circulating EPCs home in to ischemic lesions
and evoke vasculogenesis to start new blood vessel formation. On the
other hand, new immature blood vessels also sprout from existing
vessels, and they become mature vessels through angiogenesis.
