Biodegradable Drug Delivery Stents For Transmyocardial Revascularization

Transmyocardial revascularization (TMR) is a popular novel surgical treatment recently for patients with severe chronic stable angina that is refractory to coronary artery bypass graft surgery (CABG) or percutaneous transluminal coronary angioplasty (PTCA). It is paid great attention that TMR can reduce the symptoms of angina and the occurrence of ischemia, promote blood perfusion and improve heart function. But the myocardial channels are closed soon after the TMR procedure because of blood clotting. The initial channels cannot remain long-term channel patency and there is little direct blood flow through channels created. The combinations of stent and TMR are applied by arraying drilling in ischemia myocardium and putting the stent into the transmyocardial channel. Thus, they can keep long-term channels patency to improve myocardial perfusion.Angiogenic growth factor can induce angiopoiesis throughout the ischemic tissue, build collateral circulation and stimulate blood vessel growth. Therapeutic angiogenesis of growth factor have been applied to treat the ischemic heart disease and improve blood perfusion of tissue. The strategies of combining TMR with therapeutic angiogenesis augment desired experimental and clinical effects on the therapy of ischemic heart disease. They are available to recovery the region myocardial function by promoting blood perfusion and improve the formation of arterial blood. Because of the short half-life and poor target location of the growth factors, they cannot improve angiogenesis for long time continuously. Additionally, heparin has good affinity with cells and some ability of inhibiting the blood coagulation. It can enhance the biological activity and the half-life of growth factors. So the application of heparin modified stents in TMR channel can not only avoid the occlusion of TMR channels but also prevent the thrombosis and improve the formation of blood vessel endothelium to build the blood vessel linked with fine structure of endothelium. The approach can compensate the deficient of blood supplement and enhance the effect of myocardial revascularization.Up to now, there is few report about the transmyocardial stent. Other stents cannot satisfy the need of myocardial revascularization and carry the protein drugs, therefore the transmyocardial stent need to be devised especially. In this paper, the transmyocardial biodegradable drug delivery stents were studied. The stents were prepared using poly (ε-caprolactone)(PCL) and poly (D, L-lactide-co-glycolide) (PLGA) as the materials of stents by electrospinning, solution spraying or melting extrusion. The drug delivery system of PLGA was discussed. The PCL/PLGA drug delivery stents were developed by the method of embedding or compounding bilayered materials. The relations of function and structure of stent were discussed. The kinetics of drug delivery were tested and analyzed. The anticoagulated blood films of heparin modified PLGA were prepared by covalent bonding and then were checked by structure analyses. The hydrophilicity and anticoagulant properties of film were evaluated. At last the transmyocardial biodegradable drug delivery stents were prepared by optimization of all above methods .The effects of biodegradable drug delivery stents in improving revascularization and blood perfusion were evaluated by analyses of new vessels densities, histochemical stain, echocardiography, and single photon emission computed tomography (SPECT). The results are shown as follows. The melting extrusion PCL stents can sustain the pressure of myocardial muscle and keep TMR channels patency. The PCL/PLGA stents cannot only avoid the TMR channels closed but also delivery drug for long time. The heparin modified PLGA film can afford the property of anticoagulated blood. The animal experiments show the therapeutic effects of combination stent with TMR in vivo. The experimental results show the drug stents can recovery partly the function of ischemia cardiac muscle, keep TMR channels patency for a long time, enhance the densities of new vessels, improve blood perfusion and heart contraction, and encourage myocardial revascularization.Transmyocardial biodegradable drug delivery stents can not only avoid the occlusion of myocardium channel but also prevent the thrombosis and improve the formation of blood vessel endothelium. The application of the stent will be an opinion method of TMR. It can produce a marked effect in the therapy of ischemia heart disease and afford the necessary basis to fully myocardial revascularization. Moreover, the stent can be extended to the application of other conduit stents such as blood vessel stent, bile duct stent, esophagus stent and urethra stent.