Biomedical Engineering Reference
In-Depth Information
tissues. The extracellular composition and physical features of tissue greatly vary based on
tissue type and its physiological properties. Therefore, chitosan-based biomaterials should
be constructed according to the characters of tissue. In this section, applications of
chitosan-based biomaterials in blood vessel, skin, cartilage, bone, nerve, and liver tissue
are introduced.
9.5.1 blood Vessel
Cardiovascular disease, especially coronary artery disease, remains the leading cause
of mortality all over the world, which has led to an increase in the economic and social
burden of such diseases. When diseased arteries need to be replaced, the common clinical
solution for surgeons is to use autologous grafts such as mammary artery or saphenous
vein. However, these tissue sources may be inadequate or unavailable, and their harvest
adds time, cost, and the potential for additional morbidity to the surgical procedure.
A tissue-engineered blood vessel has been considered as an optimal alternative for a blood
vessel substitute. The first tissue engineered blood vessel substitute was created by
Weinberg and Bell in 1986 [81]. Current artificial vascular grafts are made of Dacron
(poly(ethyleneterephthalate)) or expanded polytetrafluorethylene. These vascular grafts
perform well at diameters >6 mm. However, owing to thrombus formation and compliance
mismatch, none of these materials have proved suitable for generating small-diameter
grafts (<6 mm) that would be required to replace the saphenous vein, internal mammary
or radial artery as a vascular substitute [82].
The artery wall contains three layers. The outermost layer is the adventitia and is com-
posed of collagen-rich connective tissue containing few elastic fibers. The middle layer
consists of SMCs arranged in circumferential and more elastic fibers. The innermost layer
is a monolayer of ECs. The theory of blood vessel tissue engineering can be applied by
using two approaches [83]. One approach is the coculturing of SMCs with biomaterials and
lining the lumen with ECs. The second approach is designed to provide a graft constructed
of a material that would provide the required mechanical properties on the implant, but
would also facilitate infiltration of host cells into the vessel and tissue remodeling. Based
on this, a chitosan-based scaffold can be employed as a vascular substitute. The size of
vascular cells is ca. 60-200 μm, which requires that the pore size of the chitosan-based
scaffold is 100-300 μm. In addition, to provide appropriate microenvironments for the
growth of SMCs and ECs, some proteins or polymers are usually introduced into chitosan-
based networks. For example, chitosan-collagen porous and fiber scaffolds, which have
the advantage of having similar components and architecture as the ECM, can improve
the attachment and proliferation of vascular cells and provide a suitable cell environment
for cells secreting more ECM [22,84]. Zhang et al. [85] developed a sandwich tubular chito-
san-gelatin scaffold. The inner and outer surfaces were the chitosan-gelatin complex, and
the middle surface was chitosan. This structure is similar to the natural blood vessel tis-
sue. This chitosan conduit should have enough suture-retention strength to withstand
in
vivo
anastomosis forces. Moreover, it is suitable for the proliferation of SMCs.
Incomplete endothelialization and SMC hyperplasia are two problems contributing to
the poor performance of existing small-diameter vascular grafts. SMC hyperplasia is one of
the primary causes of failure in small-diameter vascular grafts [86]. Therefore, the bioactive
chitosan-based scaffold should combine some materials to both enhance the rate of endothe-
lialization and specially inhibit the migration of smooth muscles to the graft lumen; mean-
while, the scaffold cannot decrease the bioactive functions of SMCs. Chitosan supported the
proliferation of both vascular cell types, but also retarded SMC growth to a greater extent
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