Biomedical Engineering Reference
In-Depth Information
causes of these processes. These limitations arise due to precise lack of controlled stem-cell
proliferation and survival both prior and subsequent to transplantation. It has been docu-
mented that biomaterial modification on the nanoscale improves cell and tissue response to
the implanted biomaterials. However, before coming to the use of nanotechnological
approaches in cardiovascular engineering, it is important to understand why nanotech-
nology is important for the success of cardiovascular tissue engineering.
Heart is an ensemble of different cell types embedded in the complex and well-defined
structures of the ECM and arranged in nanoscale topographical and molecular patterns.
Various types of ECM are found in all cardiovascular tissues, including myocardium, heart
valves, and arterial and venular vascular systems. The biochemical, electrical, and mechanical
functions of the heart are distinctively dependent on the biological nanostructures of the
ECM, information about which is crucial for cardiac tissue engineering [31]. The ECM does
more than just provide structural support to the cells. The heart's three-dimensional ECM
network is composed of an intricate, micro- and nanoscale interweaving pattern of fibrillar
collagen and elastin bundles that form a dense, elastic mesh with proteoglycans and with
adhesive and nonadhesive molecules [32]. The myocardial collagen matrix mainly consists of
type I and III collagens, which form a structural continuum. Collagen type I fibers mainly
provide structural support and give the heart properties that include stiffness and resistance
to deformation. The collagen type III fibers seem to play an important role as a link between
contractile elements of adjacent myocytes, carrying some information useful for cell function.
Similar to the myocardium, the vascular endothelium lies on the basement membrane, a type
of ECM that separates the endothelial cells from the underlying connective tissue and is
mainly composed of type IV collagen and laminin nanofibers embedded in heparin sulfate
proteoglycan hydrogels. The matrix that underlies the vascular smooth muscle cells also
comprises nanosized biological cues and structural materials. These features are critical and
should be restructured in blood vessel tissue-engineering scaffold designs.
The complex and specialized features of the myocardium and valvular tissues present
significant obstacles for the creation of functional tissue-engineered implants for cardiac
intervention. The implant transplantation in an injured heart tissue, should force the
cardiomyocytes to couple mechanically to each other, and to form elongated and aligned cell
bundles that interact with each other or with neighbouring capillaries and nerves. The intri-
cate nature of the vessels also creates a tremendous engineering challenge to resupply
implanted and growing tissues with a functional microvasculature after disease, injury, or
surgery. Therefore, an ideal scaffold must mimic the natural architecture of the cardiovascular
microenvironment. Natural polymers derived from ECM, such as arginine-glycine-aspartate
(RGD), collagen, and gelatin on their surfaces can facilitate cell adhesion and maintain cell
differentiation and are advantageous for tissue-engineering applications. However, these
materials do not possess sufficient mechanical strength, unless they are chemically cross-
linked to degrade rather rapidly in the body. Nanotechnological tools help in the design of
advanced nanocomposite scaffolds, for tissue engineering, that can better mimic the ECM.
The use of micro- and nanoscale techniques to design polymeric nanofiber scaffolds that
recapitulate the
in vivo
environment or stem-cell niches, the microenvironment for the mainte-
nance and regulation of stem cells, have enabled researchers to control the proliferation,
differentiation, and maturation of cardiovascular cells.
Polymeric Nanofiber Scaffolds
The unique properties of polymeric nanofibers make them a valuable tool for cardiovas-
cular tissue engineering. The term “nanofiber” is typically used to describe fibers with diam-
eters ranging from 1 to 1000 nm [33]. The small diameter of nanofibers closely matches the
