Tissue Engineered Vascular Grafts: New therapy for Coronary Revascularization

Despite 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.

During 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. [1]

The 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 [2]. The graft is now ready for implantation.

After 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.

The 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.

Implanting 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. [3] Looking forward TEVGs can be applied to the whole vascular system including arterial venous graft for Dialysis.