Biomedical Engineering Reference
In-Depth Information
tissue has been damaged. In this regard, bone-marrow-derived endothelial progenitor cells
(EPCs) isolated from peripheral blood and/or bone marrow have shown incorporation into
sites of physiological neovascularization in the endothelium after either systemic injection
or direct intramyocardial transplantation in animal models and of peripheral limb ischemia
and myocardial infarction [11-13]. Currently, the use of genetically modified EPCs is thus
being explored as part of a strategy to restore cardiovascular function via the processes of
therapeutic angiogenesis and arteriogenesis [14].
Cardiac Tissue Engineering
Cardiovascular cell therapy presents a novel approach to arrest cardiac dysfunction but cell
therapy alone is not sufficient. Regenerative strategies must lead to electromechanical
integration into the heart that arrests adverse myocardial remodeling and improves contrac-
tility of the diseased heart. Tissue engineering uses the principles of cell transplantation,
materials science, and engineering for the development of biologic substitutes that can
restore and maintain normal function of the damaged or lost tissue. Various approaches are
used for cardiovascular tissue engineering (Table 16.1).
Scaffold-free cell sheets are the simplest form of engineered cardiac tissue, which are generated
by culturing cells on temperature-sensitive polymer surfaces and that allow detachment of
intact cell monolayers without the use of enzymes [15]. When such cell sheets are layered one
upon another, the cells form junctions and gradually establish signal propagation and contractile
function. To enhance vascularization, endothelial layers can be placed between the myocyte
layers and implanted in a series of surgeries to allow time for the establishment of blood perfu-
sion. Many groups have adopted this technology and tested it in various animal models [16].
Another approach to scaffold-free tissue engineering has been recently explored by Stevens
et al
. (2009) using embryonic stem-cell-derived cardiomyocytes [17]. Notably, cell aggregation
alone has been shown to be sufficient to generate synchronously contracting cardiac tissue.
Another approach in cardiovascular engineering is to repopulate the decellularized native
tissue. Decellularized rat hearts can be reseeded with cardiomyocytes and endothelial cells,
resulting in the establishment of contractile activity (approximately 2% of normal) [18].
Decellularization of tissues removes all cells while leaving the extracellular matrix (ECM)
with largely preserved composition, architecture, and mechanical properties [19]. Such
decellularized tissues provide a native-like environment for cells to orient, attach, couple
with each other, and form a tissue structure while remodeling their environment. Exchange
of nutrients and oxygen throughout the depth of the tissue is maintained by medium
perfusion through the heart's vasculature.
The final approach in cardiovascular tissue engineering is the biomimetic approach that
entails seeding of the cells onto a scaffold before injecting into the myocardium to create an
in situ
engineered cardiac tissue. Scaffolds provide temporary mechanical support that
allows the tissue to grow in three dimensions while the cells undergo spatial tissue reorgani-
zation. An ideal tissue engineering scaffold used to create an engineered myocardial patch
should be: (i) highly porous with large interconnected pores (to facilitate mass transport);
(ii) hydrophilic (to enhance cell attachment); (iii) structurally stable; (iv) degradable (to
provide ultimate biocompatibility of the tissue graft); and (v) elastic (to enable transmission
of contractile forces), nonimmunogenic, and have the ability to differentiate into mature,
functional cardiomyocytes. Scaffold structure determines the transport of nutrients, metab-
olites and regulatory molecules to and from the cells, whereas the scaffold chemistry has
an important role in cell attachment and differentiation. Mechanical properties of the scaf-
fold should ideally match those of the native cardiovascular tissue, providing mechanical
