over 50 years of research in the field of Synthetic Materials, native
Vein and Artery segments are most commonly used for Revascularization
procedures in Cardiac Surgery. Unfortunately suitable Veins or Arteries
are not always available for peripheral or Coronary Revascularization,
on the other hand artificial grafts do not grow with the body and
frequent replacement is must. More over artificial grafts are
susceptible to infection, poor durability and calcification when being
attacked by the immune system. But the development of functional Tissue
Engineered Vascular Grafts (TEVG) using tissue engineering techniques
and engineering principles has the potential of tremendously effecting
Coronary and Peripheral Artery Bypass Surgeries.
initial days of TEVG development, researchers were using vascular mixed
cells for grafting. However, the cost and manpower for harvesting and
culturing the cells was too burdensome. To overcome such problem Dr.
Toshiharu Shinoka and Dr. Christopher Breuer of Yale New Haven Hospital
have developed a novel therapy for Coronary Revascularization. They
have utilized an innovative, highly efficient method for creating TEVGs.
They took a biodegradable synthetic Scaffold, made of the same material
as absorbable sutures and seeded the individual’s own cells onto it.
The scaffold degrades by hydrolysis, ultimately leaving only the living
vessel generated from seeded cells in the patient. The unique scaffold
material is vital to the process because it is able to degrade in
everyone and offers little variability.
construction of TEVG starts with harvesting the cells for grafting by
bone marrow aspirate, where a needle is put through the cortex of the
Spinal Bone and Marrow. The Marrow is drawn up and separated by density
centrifugation. This yields Bone Marrow dry mononuclear cells that are
directly seeded onto the scaffold by pipetting. Scaffold used are
composed of polyglycolic acid and epsilon-caprolactone/L-Lactide.
The seeded scaffolds are then incubated in the patient’s plasma for two
hours in order to attach cells to the scaffold . The graft is now ready for implantation.
implanting TEVGs in lambs, Dr. Breuer and Dr. Shinoka found that their
grafts were functional, actually growing in size and remodeling
themselves as valves in the host. But the surprising result was that
seeded stem cells were no longer the part of neovessels but are replaced
by host cells mainly endothelial cells and Smooth Muscle cells. Thus,
TEVG vessel formation was governed by a paracrine effect, where the
seeded cells send a message causing a cascade of events, ultimately
resulting in a blood vessel free of any artificial matter.
mechanism of vascular regeneration lies in triggering inflammatory
mechanism by secreting monocyte chemoattractant proteins by seeded
cells, which results in monocyte invasion. This invasion results in
recruitment of host monocytes on scaffold. Then recruited host cells
release a different series of cytokines, such as VEGF and PDGF, which
further recruit actual cells that compose the blood vessel. Simultaneous
to cell recruitment and tissue formation, the scaffold degrades so that
only a blood vessel remains.
TEVGs in animals have shown promising results, but the only problem
encountered is graft stenosis or constricting, which can be easily
treated by an Angioplasty. Application of TEVG in Congenital Heart
Surgery is promising and many laboratory researches are ongoing in this
direction. Yale New Haven Hospital and Yale University School of
Medicine are involved in Pilot scale study for clinical use of TEVG in
Congenital Heart Surgery. This study is under Phase I clinical trial
from 2008. Looking forward TEVGs can be applied to the whole vascular system including arterial venous graft for Dialysis.
Yale Scientific Magazine, Sudhakar Nuti, 2/10/2010