Biomedical Engineering Reference
In-Depth Information
cells throughout a large tissue construct. Moreover, the seeding of a scaf-
fold with endothelial cells does not necessarily result in the development
of new blood vessels in vitro , because this process depends on the coor-
dinated release of a variety of signaling factors such as vascular endo-
thelial growth factor (VEGF) and platelet-derived growth factor (PDGF)
and involves other cell types, including smooth muscle cells and peri-
cytes, which are normally found under in vivo conditions but not neces-
sarily in vitro [180]. Recent biomimetic technologies have improved cell
culture and seeding techniques for the development of tissue constructs,
which bear their own intrinsic vascular system before implantation and
engraftment.
6.7.2.3 Inosculation
Inosculation is characterized by a coordinated interaction between the
implanted preformed microvascular network and the microvasculature
of the host site. It was previously suggested that the vessels within skin
grafts merely provide a conduit for ingrowing wound bed vessels, what
is known as “internal inosculation,” where the host vasculature is play-
ing the active role and inosculation takes place inside the prevascularized
graft [181].
In contrast to this mechanism of internal inosculation, recent studies
provide evidence that the preformed microvascular network actively con-
tributes to the process of graft revascularization leading to “external inos-
culation” [182].
It should be mentioned here that inosculation will not only change
micro hemodynamics and oxygen distribution within a prevascularized
tissue construct, but will also open the door for infi ltrating leukocytes and
other infl ammatory cell types. This recruitment of circulating leukocytes
into the grafted tissue will depend on their interaction with the microvas-
cular endothelium [183].
It is of importance in this context to point out that any implanted tissue
(natural or engineered) will be remodeled on implantation. The micro-
vascular network that is implanted may be completely different or absent
after remodeling in vivo [173]. Vascular remodeling, and even vascu-
lar regression, are crucial for maturation and integration after construct
implantation, yet premature vessel remodeling and regression within a
construct could become a major obstacle to maintaining in vivo developed
microvascular networks within a construct [184].
From the postulated vascularization strategies an acceptable protocol
for construct vascularization would benefi t from extrinsic angiogenesis
for small constructs (2-3mm thick), intrinsic angiogenesis for larger con-
structs wherever local vascular axes are available, and from vasculogen-
esis for large cell-loaded constructs.
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