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Biodegradable Fe-stents

#A-1841


Development in Pure Iron Biodegradable Stents: Fe-Stent, Polymer-Coated, and Drug Eluting Stents

Tech Area / Field

  • CHE-POL/Polymer Chemistry/Chemistry
  • MAT-ALL/High Performance Metals and Alloys/Materials
  • MED-DRG/Drug Discovery/Medicine

Status
8 Project completed

Registration date
08.04.2010

Completion date
11.12.2012

Senior Project Manager
Melnikov V G

Leading Institute
The Scientific Centre of Radiation Medicine and Burns, Armenia, Yerevan

Supporting institutes

  • Yerevan Institute "Plastpolymer", Armenia, Yerevan\nState Engineering University of Armenia, Armenia, Yerevan

Collaborators

  • Universidade de Coimbra, Portugal, Coimbra\nNational University of Ireland / National Centre for Biomedical Engineering Science, Ireland, Galway\nSogang University, Korea, Seoul\nUniversita di Pisa / Dipartamento di Patologia Sperimentale, Biotecnologie Medicine, Infettivologia ed Epidemiologia, Italy, Pisa\nGraz University of Technology / Institute for Chemistry and Technology of Materials, Austria, Graz\nLaval University / Département de Génie des Mines, de la Métallurgie et des matériaux, Canada, QC, Quebec City

Project summary

Project related studies are aimed at research on biological compatibility and degradation of iron devices in contact with blood under conditions in vitro and in vivo.

The urgency of this scientific direction is conditioned by the fact that currently existing limitations to apply drug eluting stents (DES) have renewed the interest in biodegradable stents. Such problems as late restenosis, mechanical occlusion of the lateral branch ostium, worsening of stents adhesion to vessel walls signify to the necessity to develop entirely dissolving stents. Moreover, there is still an open question: what is the reason for the foreign device (metallic stent) to remain in a coronary bed.

Polymeric biodegradable stents have demonstrated several limitations. Their strength is lower when compared to metallic stents. These stents are radiolucent, which may impair accurate positioning. Furthermore, it is difficult to deploy the stent smoothly and precisely without fluoroscopic visualization.

Interest in metallic degradable biomaterials research has been growing in the last decade. Both scientific journals and patent databases record a high increase in publications in this area. Pure iron is a potential material for coronary artery stents based on its biocorrodible and nontoxic properties. Mechanical properties of iron are comparable with those of available metal alloys for permanent cardiovascular implants.

The main goal of the Project is to design a device that due to combination of pure iron and biodegradable polymer coverings/coatings will possess properties of DES alongside with the ability to complete degradation.

Studies on biocompatibility of iron stents in animal experiments demonstrate that stents made of biocorrodible iron are safe. In some of the measured parameters, such as intimal thickness, intimal area, and percentage occlusion, there was a trend in favor of the iron stents. However the degradation characteristics of pure iron in vivo and in vitro are not yet clear. The iron stents could lose their mechanical stability prematurely due to their corrodible degradation.

Currently the search is actual for iron cardiovascular stents of moderate and homogenous degradation. In particular, electroformed iron demonstrated more rapid degradation than cast iron. According to recent data, the rate of degradation of pure iron in vivo is significantly slower than in vitro. The improved corrosion resistance and biological compatibility was achieved by obtaining thin Fe-O films on pure iron by plasma method.

In the present Project model stents obtained by laser cut of pure iron (99.9% iron, “Yerevan Plant of Pure Iron”) will be studied. For prevention of biodegradation at the initial stage after implantation the stents will be covered by polymer films. All studies will be performed in comparison with stents made of stainless steel.

Previously, the hemocompatible synthetic polymer coverings on metal stents (SS, Ti) were studied within the frames of A-1358 Project. The experiments in animals demonstrated that the period of polymer coverings dissolution might vary from 1 week to 3 months depending on the type of a polymer. The obtained results allow to hope that the selection of a polymer covering for the iron stent was properly done. There is a necessity to continue the research aimed at design and development of new polymer covering; the following essential features should be embraced: hemocompatibility, hydrophobicity, anti-inflammability, conformity to the stent surface, flaking resistance, sterilizability and biodegradability.

For prevention of vessels restenosis that is frequently observed after implantation of stents Project related research involves plans to study the kinetics of controlled release of the antiproliferative medicinal substance from the polymer covering.

The stage-by-stage scheme will be used for project implementation: polymer synthesis; preparation of model stents; selection of polymers according to physical-chemical and physical-mechanical properties; obtaining coverings with medicinal substances; studies on short- and long-term contact of the material with blood in static and dynamic conditions; selection of materials according to test results under conditions in vitro; sterilization; toxicological analysis; testing in vivo; selection of the material.

The obtained results will become an input in the problem of optimal DES development. Another step will be taken to demonstrate if biodegradable stents can eliminate currently used stents and change, the current practice in which numerous patients chronically bear metal in their coronary arteries.

The use of a combination “Fe – stent with biodegradable coverings” would allow to develop devices that possess the feature of DES and are entirely degradable.

Design and development of an optimal DES requires the multidisciplinary approach, therefore the research team comprises biologists, chemists, physicists having the experience of research activity in ISTC projects.

At the Scientific Center of Radiation Medicine and Burns the required scientific and technical basis for carrying out medical and biological studies, as well as the vivarium are in place. The scientific personnel has the extended experience in studies on blood clotting system and thrombocytopoiesis. The thematic scope of research on blood coagulation performed at the Centrer in case of combined radiation/thermal injuries of wartime was an integral part of the activity Unified Problem Commission (USSR Ministry of Defence and Ministry of Health at the Institute of Medical Radiology, Obninsk, Russia).

The role of collaborators will include providing consultations and assistance upon carrying out studies, as well as arrangement of joint workshops. Under the Project it is planned to establish close collaboration with Professor A. Pompella, the Collaborator from Pisa University (Italy), in the area of studies on cytotoxicity tests in vitro for cell viability tests, including smooth muscle cells, because inhibition of proliferative activity is important for prevention of vascular restenosis.

In accordance with ISTC goals the following tasks will be performed: Reorientation of activity performed by scientists earlier engaged in defence area towards solution of public health problems; Integration of scientists from Armenia into the International research collaboration.


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