Electrospinning is commonly used to generate polymeric scaffolds for tissue engineering.
Using this approach, we developed
a small-diameter tissue engineered vascular graft (TEVG) composed of poly-ε-caprolactone-co-L-lactic
acid (PCLA) fibers and
longitudinally assessed its performance within both the venous and arterial circulations
of immunodeficient (SCID/bg) mice. Based
on in vitro analysis demonstrating complete loss of graft strength by 12 weeks,
we evaluated neovessel formation
in vivo over 6-, 12- and 24-week periods. Mid-term observations indicated physiologic
graft function,
characterized by 100% patency and luminal matching with adjoining native vessel in
both the venous and arterial circulations. An
active and robust remodeling process was characterized by a confluent endothelial
cell monolayer, macrophage infiltrate, and
extracellular matrix deposition and remodeling. Long-term follow-up of venous TEVGs
at 24 weeks revealed viable neovessel
formation beyond graft degradation when implanted in this high flow, low-pressure
environment. Arterial TEVGs experienced
catastrophic graft failure due to aneurysmal dilatation and rupture after 14 weeks.
Scaffold parameters such as porosity, fiber
diameter, and degradation rate informed a previously described computational model
of vascular growth and remodeling, and
simulations predicted the gross differential performance of the venous and arterial
TEVGs over the 24-week time course. Taken
together, these results highlight the requirement for in vivo implantation studies
to extend past the critical
time period of polymer degradation, the importance of differential neotissue deposition
relative to the mechanical (pressure)
environment, and further support the utility of predictive modeling in the design,
use, and evaluation of TEVGs in
vivo .