Development of zinc-iron biodegradable vascular stents
Project Status: 3 Approved without Funding
Duration in months: 36 months
Objective
The Project aim. This project aim is development of electroformed degradable metal materials and use of such materials as vascular scaffolds and other medical devices.
The main objects are development of iron-zinc-based (Fe-Zn) stent materials as candidates for biodegradable biomaterials with superior mechanical properties and degradation behaviors. In the present study, a novel biodegradable stent material will be made by layered electroforming. Project related studies are aimed at research on biological compatibility and degradation of metal devices under in vitro and in vivo conditions. Current status. The 9th Symposium on Biodegradable Metals (Italy, Bertinoro, August 27 - September 1, 2017) gave careful consideration to the “Current status on research of biodegradable metals”. The majority of present-day research works on biodegradable materials were dedicated to magnesium (Mg) and its alloys. Orthopedic, dental, and cardiovascular stent applications of Mg-alloys are under the investigation in Japan and China. Materials based on Mg-alloy were approved from Korea Food and Drug Administration (KFDA) for the first human clinical trial of orthopedic biodegradable metallic implant devices in Korea.
Pure iron (Fe), magnesium (Mg), zinc (Zn) and their related alloys have been investigated as promising candidates for degradable stenting applications. Zinc has come to the attention of researchers in the last few years as a possible vascular scaffold material. Zinc is a very important element for proper functions of human body. It is found that the sequence of corrosion rate of pure metals from high to low is: Mg > Fe > Zn. Ultimate strength for pure Zn is a little higher than that of Mg; however, it is a brittle material. Pure Zn may be suitable for bone fixation but improper for stent applications, in which good ductility is needed. Pure Fe possesses the most suitable mechanical properties for coronary stent material. The A-2115 ISTC project results showed that electroformed iron was a suitable metal for the production of stent with a large period of in vivo degradation. The obtained value of iron degradation of electroformed iron in direct contact with blood of animals allows to assess complete degradation during a period of 1.5 - 2 years. The slow degradation rate of iron does not match the clinical requirement in some cases. Another limitation for Fe stents is potentially hazardous iron oxide products. The release of iron ions during dissolution may cause side effects like oxidative stress and inflammation in the tissues in contact with the implant. A black deposit was revealed in vessel walls after complete iron degradation. Product of iron degradation in form of Fe3+ oxide was observed in some tests.
There is a necessity to continue the research aimed at design and development of new biodegradable stents which do not produce any negative local or systemic side effects in vivo. The electroformed layered Fe-Zn degradable stent may be a promising alternative with optimal necessary time degradation. Probably, the new material must not produce Fe3+ ions. The project’s influence on progress in this area. The majority of stents, including metallic biodegradable stents, are fabricated from metallic ingots by casting and thermomechanical treatment. Recently powder metallurgy process has been used to produce Zn-, Fe-, and Mg-alloys biodegradable stents. Electroforming is excellent method for manufacturing of iron biodegradable materials. The next step of stent fabrication is laser cut from mini-tubes. The newly proposed Project will be focused on electroforming fabrication of Fe-Zn composites as candidates for biodegradable stent materials. For the first time electroforming will be used to produce Fe-Zn composite stents directly on cylindrical forms with small thickness without laser cutting. Development of optimal stents requires a systematic multidisciplinary approach to optimize the stent metal, stent design, polymer coatings and the active agent (drugs). In the present Project biodegradable polymer will be obtained and used as drug eluting coating (covering) of metal surfaces. The participants’ expertise. The project implementation team will include scientists, who took part in ISTC A-2115, A-1841, A-1358, and A-948 projects. The scientists have significant experience in developing pure iron stents. The researchers are highly professional in conducting experiments in laboratory animals. Expected results and their application. Research on biodegradation stents with adjustable speed will have the practical importance in the field of safe stents design and development. Electroforming method will be used for obtained other metal composites, for example Fe-Ag. The developed metal and polymer materials to be developed are promising for future absorbable stents, surgical sutures and biodegradable orthopedic implants. Scope of activities. Comprehensive evaluations on the in vitro and in vivo corrosion behaviors will be studied.
The following activities will be implemented under the Project:
- Preparation of electroformed iron and Fe-Zn
- Obtainment of model stents;
- Synthesis and selection of biodegradable elastic polymers to be used as stents coatings;
- Coating the stents with drug eluting biodegradable polymer;
- Selection of applicable sterilization techniques;
- Comparison of Fe and Fe-Zn biocompatibility;
- Comparison of Fe and Fe-Zn degradation rates.
Participating Institutions
LEADING
Scientific Centre of Radiation Medicine and Burns (SCRMB)
