Fabrication of resorbable microporous intravascular stents for gene therapy applications

The authors have produced resorbable, microporous endoluminal stents from Poly-L-lactic acid (PLLA)/Poly epsilon-caprolactone (PCL) blends. Both helical and tube stent designs have been obtained by solvent casting and flotation-precipitation fabrication techniques. A range of PLLA/PCL blend ratios and process variables were employed to investigate their influence on mechanical properties, porosity, and degradation rate. Polymer blends with higher PLLA proportions exhibit higher elastic moduli and ultimate tensile strength, and lower elongation, porosity, and degradation rates than do materials with higher PCL content. Stents with suitable mechanical properties for deployment and support of the vessel wall were obtained. Poly(ethylene oxide) was incorporated into these devices using an acid swelling technique, opening the pore structure and improving the hydrophilic character, thereby enabling the uptake of recombinant adenoviral vectors. The 50:50 PLLA/PCL blended stents were impregnated with recombinant adenovirus (AdCMB beta Gal, encoding a nuclear localizing variant of Escherichia coli beta-galactosidase). Cultured CV-1 cells incubated with stents impregnated with the recombinant virus expressed nuclear localized beta-galactosidase activity, confirming that absorbed virus is released from the matrix in an infectious form, with kinetics suggesting that genetically enhanced endovascular devices of this design are feasible.