Helen M. Nugent and Elazer R. Edelman* Pages 529 - 544 ( 16 )
It has become apparent that mechanical interventions designed to alleviate atherosclerotic vascular disease are beset by accelerated vascular diseases of their own. A multitude of agents have been directed against one or more of the cellular events thought to be involved in this process known as restenosis. Most of these agents suppress smooth muscle cell growth in tissue culture and in animal models, and yet no drug to date has shown any demonstrable benefit against human disease. This may be due to the suboptimal manner in which these drugs were administered. It has been demonstrated that far more beneficial effects are observed if one matches the delivery of a drug to the natural release of endogenous growth regulators. Controlled release of heparin from polymeric matrices inhibited smooth muscle cell proliferation following injury to vascular endothelium in a manner more efficient than in systemic administration. Moreover, the biologic control achieved by the endothelium is not due to one or several compounds, but rather to the concomitant presence and complimentary activity of all the cell-based products. Perivascular implantation of tissue engineered endothelial cell implants around injured arteries reduced intimal hyperplasia far better than isolated administration of heparin. Thus the coupling of polymer based drug delivery technology and tissue engineering with the science of molecular and cell biology provides a means to understanding the paradox of restenosis and even potential therapies.