Page 41 - Read Online

Polykandriotis et al. Plast Aesthet Res 2018;5:37 I http://dx.doi.org/10.20517/2347-9264.2018.52 Page 7 of 10

will allow cells within a matrix to survive the critical time frame until vascularization has taken place and
[10]
nourishing substances can be delivered from the recipient into the bioartificial construct .

[46]
Other studies have used Matrigel as a matrix for the AV-loop and showed enhanced neovascularization .
However, for potential clinical applications, matrigel, extracted from the Engelbreth-Holm-Swarm mouse
sarcoma, is not a matrix of choice in patients. In contrast, fibrin as a matrix is a commercially available
product that has been in clinical use for decades. It possesses several advantages as a potential matrix,
[47]
some of which have to do with the interplay between controlled fibrinolysis and onward angiogenesis .
We have shown that the kinetics of neoangiogenesis and neovascularization can be enhanced by addition
of soluble growth factors which boost neovascular growth [48,49] . Fibrin is one possible carrier and has been
repeatedly demonstrated to be a suitable carrier for cultured cells, such as in cultured human keratinocyte
transplantation [50,51] and muscle TE.

The formation of new blood vessels is a fundamental process in tissue regeneration and in organ
development. Angiogenesis is most frequently associated with inflammation, along with hypoxic conditions
and cell infiltration, although it remains elusive how molecular and cellular mechanisms underlying
inflammatory reactions in detail regulate angiogenetic processes. Hypoxia-inducible factors (HIFs), HIF1
alpha and HIF2 have been investigated as potential indicators of neoangiogenesis in various contexts [52-55] .

The influence of mesenchymal stem cells might also play a critical role in neovascularization [56,57] . It has been
hypothesized that angiogenesis and vasculogenesis can be studied in the context of TE with regard to similar
processes that occur in tumorigenesis and that TE models could help to further clarify these biological
[58]
events . Phenomena of intimal hyperplasia and thickening of the vessel wall during neoangiogenesis have
been well described [59-61] . It has also been noted that myointimal thickening leads to a continuous decrease
[60]
in the luminal diameter , which is an explanation for the decrease in the luminal vessel diameters that
we observed following day 7 in our experiments. It is not clear why the intepositional vein graft shows the
highest increase in angiogenesis and if there is a critical length of such an AV axis that would limit the
clinical applicability. From clinical data in using long bypass grafts for free flap transplantation we suggest
[16]
that the length of an interpositional vein in such circumstances graft is limited . If bioartificial vessels,
which would be desirable in terms of minimizing the donor site morbidity, will become clinically available
and will offer the same capacity of sprouting and neoangiogenesis remains yet open.

CONCLUSION
Although the AV-loop model is rather complex and time consuming, it offers the unique advantage of
studying neoangiogenesis and vasculogenesis in a controlled environment, to observe the mechanisms of
vessel arborisation and remodelling, and to investigate changes in the perfusion pattern in correlation to the
specific segments of the AV-loop.

DECLARATIONS
Acknowledgments
We want to thank Xue-Hong and Hans Georg Geis, Dr. Hans Peter Mall, and Mrs. Boya Marshall for their
ongoing support of our research.

Authors’ contributions
Prepared this manuscript: Polykandriotis E
One of the first to establish the AV Loop Model: Polykandriotis E, Arkudas A, Horch RE
Edited the manuscript and provided valuable illustrations material, developed and established the AV
Model: Arkudas A