Biomedical Engineering Reference
In-Depth Information
maturation and connection with the host blood vessels is ultimately a
limit to the scale of engineered viable tissues. As a unique technique,
this step-by-step procedure based on cell sheet-stacking technology
seems to open the possibility for fabricating viable tissues with an
appropriate vascular network formation and the means for scaling
up (Fig. 6c.5) [3]. Triple-layer cardiac cell sheets are repeatedly
implanted after waiting for sufficient vascular formation within
the previously implanted tissues. The result is a successfully
fabricated, synchronously beating, thick myocardial tissue with
sufficient microcapillaries made from 10 transplantations of
triple-layer constructs (for a total of 30 sheets) to form a 1 mm
thick pulsatile myocardial tissue. Furthermore, when triple-layer
grafts are transplanted repeatedly over a surgically connectable
artery and vein in the leg, the multilayer constructs are supplied
with blood from the thick artery and vein. The constructs can then
be successfully resected with the connectable blood vessels and
ectopically transplanted in the neck with direct vessel anastomosis.
This multistep procedure may indicate one possible solution for
scaling up of bioengineered tissues.
6c.8
Future Views of Vascularization
Technologies
As described above, various technologies have already demonstrated
the potential for fabricating functionally vascularized myocardial
tissues. Vascular composing cell coculture has significantly advanced
research in the field of vascularization of engineered tissues, and the
in vivo regeneration power is helpful for the formation of functional
blood vessels. Now, one of the next key issues is how to initiate and
accelerate the tubularization of an endothelial cell network within
the construct. Since primary ischemia before perfusion limits
tissue survival, rapid perfusion through a prefabricated luminal
structure is necessary. A step-by-step procedure is one possible
solution, but the necessity for multiple surgeries could be a serious
clinical problem. Another key issue is how to engineer thicker blood
vessels for anastomosis with the host blood vessels. Utilizing a host
artery and vein may be clinically acceptable; however, the perfect
fabrication in vitro of functionally vascularized myocardial tissue
