title: Development of a new biodegradable intravascular polymer stent with simultaneous incorporation of bioactive substances.
abstract: OBJECTIVE
  Due to the thrombogenicity and permanent implant nature of metallic stents, bioresorable synthetic polymers have been proposed for stents and local drug delivery systems. Bioresorbable polyesters like poly(D,L-lactide) demonstrated excellent biocompatibility in various tissues. This paper describes a novel method for the molding of these polymers. The specific CESP-process (Controlled Expansion of Saturated Polymers) is characterised by the use of the plasticizer carbon dioxide and allows the incorporation of bioactive substances at physiologic temperatures into the polymer bulk and the production of complex designed implants.
  
  
  METHODS
  The CESP-process is characterised by the exposure of an amorphous polymer to an inert gas at high pressure with a significant lower glass transition point. The plasticizing effect makes it possible to process polylactides at a temperature close to room temperature. The low process temperature constitutes a key advantage for thermally sensitive polymers and allows the incorporation of thermally sensitive pharmaceutical additives. To obtain some preliminary information on the biocompatibility, in vitro cell toxicity testing as well as drug release assessment was performed.
  
  
  RESULTS
  Different polymer sheets were produced using the CESP-process. Cytotoxicity was not observed in any molded polymer material. According to the mechanical and biocompatibility results Poly(D,L-lactide) (P-DL-LA) was investigated in the CESP-process. Finite element analysis was used to test the possible geometry of an adequate stent. A helical design was chosen and a stent-prototype was produced using the CESP-process. Peroxidase activity as an incorporated marker enzyme could be measured over 6 weeks. Different drug release profiles were obtained due to various pore sizes of the polymer.
  
  
  CONCLUSIONS
  The new CESP-process can be used to process biodegradable polymers and to mold different stent geometries without inducing cytotoxic effects to the material. Furthermore, this procedure permits the simultaneous incorporation of bioactive substances during the molding process. Drug release kinetics can be regulated by different pore sizes of the material.
authors.affiliation: Medical Clinic I, University Hospital, RWTH Aachen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Blindt
authors.forename: K M
authors.initials: KM
authors.lastname: Hoffmeister
authors.forename: H
authors.initials: H
authors.lastname: Bienert
authors.lastname: Pfannschmitt
authors.forename: G
authors.initials: G
authors.lastname: Bartsch
authors.forename: H
authors.initials: H
authors.lastname: Thissen
authors.forename: D
authors.initials: D
authors.lastname: Klee
authors.forename: J
authors.initials: J
authors.lastname: Vom Dahl
mesh_terms: D020341:Absorbable Implants; D001672:Biocompatible Materials; D001807:Blood Vessel Prosthesis; D002478:Cells, Cultured; D003198:Computer Simulation; D011091:Polyesters; D011108:Polymers; D011474:Prosthesis Design; D015607:Stents
chemical_list: D001672:Biocompatible Materials; D011091:Polyesters; D011108:Polymers; C033616:poly(lactide)