Development of high-performance stent: gelatinous photogel-coated stent that permits drug delivery and gene transfer

Abstract

Hydrogel-coated metallic stents may provide supplementary functions such as local drug delivery and gene transfer in addition to mechanical dilation function. To this end, we used a photoreactive material consisting of gelatin macromer (multiple styrene-derivatized gelatin) and carboxylated camphorquinone (photo-initiator). A few minutes of visible light irradiation of a stent after dip-coating of an aqueous solution of the photoreactive material resulted in the formation of a homogeneously crosslinked gelatinous layer on the entire exterior surface of the stent. As the metal stent, gold stents under development were used. Rhodamine-conjugated albumin as a model drug or adenoviral vector expressing bacterial beta-galactosidase (AdLacZ) as a model gene were photo-immobilized in the gelatinous gel layer. In vitro experiments using hybrid tubular tissue, which is a self-shrinkaged, vascular smooth muscle cell-incorporated type-I collagen gel, as a vascular model, showed that the immobilized dye-derivatized albumin was released on and permeated into tissues, as observed by confocal laser microscopy, and that the cells transfected with immobilized AdLacZ produced beta-galactosidase up to almost 3 weeks, as observed by x-gal staining. In preliminary in vivo experiments these drug- or adenovirus-immobilized stents were implanted in rabbit common carotid arteries. Within 3 weeks of implantation, drug permeation and gene expression in the vascular tissues were observed, indicating that the gelatinous photogel effectively serves as a matrix or coating for a bioactive stent,which permits drug release as well as gene transfer. This intraluminal approach has the potential to realize drug and gene therapy in atherosclerotic plaque.