Future - Chitosan Based Hydrogels: Functions and Applications - page 471

number of clinical applications in the field of tissue engineering is still limited. One of the
current limitations of tissue engineering is its inability to provide sufficient blood supply
in the initial phase after implantation. Insufficient vascularization can lead to improper
cell integration or cell death in tissue-engineered constructs. It is necessary to discuss the
advantages and limitations of some recent strategies aimed at enhancing the vasculariza-
tion of tissue-engineered constructs.
A critical obstacle in tissue engineering is the inability to maintain large masses of living
cells, upon transfer from the in vitro culture conditions into the host, in vivo [29]. To achieve
the goals of engineering large complex tissues, and possibly internal organs, vasculariza-
tion of the regenerating tissue is essential. A tissue more than a few millimeters in volume
cannot survive by diffusion and requires the formation of new blood capillaries to supply
essential nutrients and oxygen [30].
After implantation of tissue constructs, the supply of oxygen and nutrients to the
implant is often limited by diffusion processes that can only supply cells in the proxim-
ity of 100-200 mm from the next capillary. In order for implanted tissues of greater size
to survive, the tissue has to be vascularized, which means that a capillary network
capable of delivering nutrients to the cells is formed within the tissue. After implan-
tation, blood vessels from the host generally invade the tissue to form such a network, in
part in response to signals that are secreted by the implanted cells as a reaction to
hypoxia.
10.4.3 Functionalization for Organ regeneration
The majority of current reconstructive techniques rely on donor tissue for replacement;
however, a shortage of donor tissue may limit these types of reconstructions, and usually
significant morbidity is associated with the harvest procedure. Furthermore, the func-
tional aspects of the damaged organ are rarely replaced by these reconstructive proce-
dures, and they may even lead to complications because of the inherently different
functional parameters of reconstructed tissue.
Because the speed of vascularization after implantation is a major problem in tissue
engineering, the successful use of tissue-engineered constructs is currently limited to thin
or avascular tissues, such as skin or cartilage, for which postimplantation neovasculari-
zation from the host is sufficient to meet the demand for oxygen and nutrients [31]. To suc-
ceed in the application of tissue engineering for bigger tissues, such as bones and muscles,
the problem of vascularization has to be solved [32].
10.5 Disease Information for Drug Delivery Systems
Chitosan and chitosan derivatives, because of their excellent mucoadhesive and absorp-
tion-enhancing properties, have been extensively studied for the delivery of therapeutic
proteins and antigens, particularly via mucosal routes.
Diabetes mellitus is an endocrine disease that is related to disorders of carbohydrate
metabolism brought about by a deficiency in insulin secretion, insulin resistance, or both
[33,34]. Chitosan displays mucoadhesive property and robust physicochemical stability
that have been shown to be potentially useful for the delivery of insulin via the transmu-
cosal pathway [35,36]. The positive effect of chitosan on transmucosal delivery of insulin