Hendra Hermawan

Developments in metallic biodegradable stents

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. Biomedical implants with temporary function, such as coronary stents, are the targeted applications for this novel class of biomaterials. It is expected that stents made of degradable biomaterials, named biodegradable stents, will provide a temporary opening into a narrowed arterial vessel until the vessel remodels and will progressively disappear thereafter. Biodegradable stents made of metal have recently been progressed into preclinical tests in humans after their first introduction in early 2000s. By referring to patents and journal publications, this paper reviews the developments in biodegradable stents, with emphasis on those made of metals, starting from the first design ideas to validation testing.

Iron–manganese: new class of metallic degradable biomaterials prepared by powder metallurgy

Abstract An Fe–35 wt-%Mn alloy, aimed to be used as a metallic degradable biomaterial for stent applications, was prepared via a powder metallurgy route. The effects of processing conditions on the microstructure, mechanical properties, magnetic susceptibility and corrosion behaviour were investigated and the results were compared to those of the SS316L alloy, a gold standard for stent applications. The Fe35Mn alloy was found to be essentially austenitic with fine MnO particles aligned along the rolling direction. The alloy is ductile with a strength approaching that of wrought SS316L. It exhibits antiferromagnetic behaviour and its magnetic susceptibility is not altered by plastic deformation, providing an excellent MRI compatibility. Its corrosion rate was evaluated in a modified Hanks solution, and found superior to that of pure iron (slow in vivo degradation rate). In conclusion, the mechanical, magnetic and corrosion characteristics of the Fe35Mn alloy are considered suitable for further development of a new class of degradable metallic biomaterials.

Degradable metallic biomaterials: Design and development of Fe–Mn alloys for stents

Designing materials having suitable mechanical properties and targeted degradation behavior is the key for the development of biodegradable materials for medical applications, including stents. A series of Fe-Mn alloys was developed with the objective to obtain mechanical properties similar to those of stainless steel 316L and degradation behavior more suited than pure iron. Four alloys with Mn content ranging between 20 and 35 wt % were compared in this study. Their microstructure, mechanical properties, magnetic properties as well as degradation behavior were carefully investigated. Results show that their microstructure is mainly composed of gamma phase with the appearance of epsilon phase in alloys having a lower Mn content. The yield strength and elongation of alloys was comprised between 234 MPa and 32% for Fe-35%Mn alloy to 421 MPa and 7.5% for the Fe-20%Mn alloy. All alloys show similar magnetic susceptibility ( approximately 1.8 x 10(-7) m(3)/kg) in the quenched condition. This magnetic susceptibility remains constant after plastic deformation for all the tested alloys except for the Fe-20%Mn alloy. The corrosion rate was higher than pure iron. Among the alloys studied in this work, the Fe-35%Mn alloy shows mechanical properties and degradation behavior closely approaching those required for biodegradable stents application.

Porous Biodegradable Metals for Hard Tissue Scaffolds: A Review

Scaffolds have been utilized in tissue regeneration to facilitate the formation and maturation of new tissues or organs where a balance between temporary mechanical support and mass transport (degradation and cell growth) is ideally achieved. Polymers have been widely chosen as tissue scaffolding material having a good combination of biodegradability, biocompatibility, and porous structure. Metals that can degrade in physiological environment, namely, biodegradable metals, are proposed as potential materials for hard tissue scaffolding where biodegradable polymers are often considered as having poor mechanical properties. Biodegradable metal scaffolds have showed interesting mechanical property that was close to that of human bone with tailored degradation behaviour. The current promising fabrication technique for making scaffolds, such as computation-aided solid free-form method, can be easily applied to metals. With further optimization in topologically ordered porosity design exploiting material property and fabrication technique, porous biodegradable metals could be the potential materials for making hard tissue scaffolds.

Metals for Biomedical Applications

In modern history, metals have been used as implants since more than 100 years ago when Lane first introduced metal plate for bone fracture fixation in 1895 (Lane, 1895). In the early development, metal implants faced corrosion and insufficient strength problems (Lambotte, 1909, Sherman, 1912). Shortly after the introduction of the 18-8 stainless steel in 1920s, which has had far-superior corrosion resistance to anything in that time, it immediately attracted the interest of the clinicians.

Cytotoxicity evaluation of biodegradable Zn-3Mg alloy toward normal human osteoblast cells.

The recent proposal of using Zn-based alloys for biodegradable implants was not supported with sufficient toxicity data. This work, for the first time, presents a thorough cytotoxicity evaluation of Zn-3Mg alloy for biodegradable bone implants. Normal human osteoblast cells were exposed to the alloys extract and three main cell-material interaction parameters: cell health, functionality and inflammatory response, were evaluated. Results showed that at the concentration of 0.75mg/ml alloy extract, cell viability was reduced by ~50% through an induction of apoptosis at day 1; however, cells were able to recover at days 3 and 7. Cytoskeletal changes were observed but without any significant DNA damage. The downregulation of alkaline phosphatase protein levels did not significantly affect the mineralization process of the cells. Significant differences of cyclooxygenase-2 and prostaglandin E2 inflammatory biomarkers were noticed, but not interleukin 1-beta, indicating that the cells underwent a healing process after exposure to the alloy. Detailed analysis on the cell-material interaction is further discussed in this paper.

Degradation Behaviour of Metallic Biomaterials for Degradable Stents

The short-term need of scaffolding function of stent and the prevention of potential longterm complication of permanently implanted stent have directed to the original idea of biodegradable stent. Selecting and developing materials showing appropriate mechanical and degradation properties are key steps for the development of this new class of medical devices. Therefore, the study of their in vitro degradation behaviour is mandatory for the selection of potential candidate materials suited in vivo. In this work, the degradation behaviour of current studied biodegradable metals including three magnesium alloys (Mg, AM60B and AZ91D), pure iron and Fe-35Mn was investigated. The tests were performed in a simulated blood plasma solution at 37±0.1 oC, using three different methods; potentiodynamic polarization, static immersion, and dynamic test in a test-bench which mimics the flow condition in human coronary artery. Degradation rate was determined as ion release rate measured by using atomic adsorption spectroscopy (AAS) and also estimated from weight loss and corrosion current. Surface morphology and chemical composition of corroded specimens were analyzed by using SEM/EDS. The three degradation methods provide consistent results in corrosion tendency, where Mg showed the highest corrosion rate followed by AZ91D, AM60B, Fe-35Mn and iron. Potentiodynamic polarization gives a rapid estimation of corrosion behaviour and rate. Static immersion test shows the effect of time on the degradation rate and behaviour. Dynamic test provides the closest approach to the environment after stent implantation and its results show the effect of the flow on the materials degradation. In conclusion, the three investigated methods can be applied for screening, selecting and validating materials for degradable stent application before going further to in vivo assessments.

In vitro and in vivo degradation evaluation of novel iron-bioceramic composites for bone implant applications.

Biodegradable metals such as magnesium, iron and their alloys have been known as potential materials for temporary medical implants. However, most of the studies on biodegradable metals have been focusing on optimizing their mechanical properties and degradation behavior with no emphasis on improving their bioactivity behavior. We therefore investigated the possibility of improving iron biodegradation rate and bioactivity by incorporating various bioactive bioceramics. The iron-based bioceramic (hydroxyapatite, tricalcium phosphate and biphasic calcium phosphate) composites were prepared by mechanical mixing and sintering process. Degradation studies indicated that the addition of bioceramics lowered the corrosion potential of the composites and slightly increased their corrosion rate compared to that of pure iron. In vitro cytotoxicity results showed an increase of cellular activity when rat smooth muscle cells interacted with the degrading composites compared to pure iron. X-ray radiogram analysis showed a consistent degradation progress with that found in vivo and positive tissue response up to 70 days implantation in sheep animal model. Therefore, the iron-based bioceramic composites have the potential to be used for biodegradable bone implant applications.

Development of degradable Fe-35Mn alloy for biomedical application

As some biomedical problems require only temporary intervention, there is a clinical need for degradable biomaterials with excellent mechanical properties and controllable degradation behaviour. Although several works were carried out on both polymeric and metallic materials, no proposed degradable biomaterial fully satisfied these requirements. Therefore a new Fe-35Mn alloy has been developed as a valid and well suited alternative. The alloy was fabricated through powder metallurgy route followed by successive cold rolling and sintering cycles. This austenitic alloy exhibits a high strength and ductility, comparable to that of type 316L stainless steel. Its antiferromagnetic behaviour is not changed by cold deformation process. The alloy shows suitable degradation behaviour with a uniform corrosion mechanism and a slow release of ions that make it particularly well suited for the development of a new class of biodegradable stents.

Polydopamine as an intermediate layer for silver and hydroxyapatite immobilisation on metallic biomaterials surface

Hydroxyapatite (HA) coated implant is more susceptible to bacterial infection as the micro-structure surface which is beneficial for osseointegration, could also become a reservoir for bacterial colonisation. The aim of this study was to introduce the antibacterial effect of silver (Ag) to the biomineralised HA by utilising a polydopamine film as an intermediate layer for Ag and HA immobilisation. Sufficient catechol groups in polydopamine were required to bind chemically stainless steel 316 L, Ag and HA elements. Different amounts of Ag nanoparticles were metallised on the polydopamine grafted stainless steel by varying the immersion time in silver nitrate solution from 12 to 24 h. Another polydopamine layer was then formed on the metallised film, followed by surface biomineralisation in 1.5 Simulated Body Fluid (SBF) solution for 3 days. Several characterisation techniques including X-Ray Photoelectron Spectroscopy, Atomic Force Microscopy, Scanning Electron Microscopy and Contact Angle showed that Ag nanoparticles and HA agglomerations were successfully immobilised on the polydopamine film through an element reduction process. The Ag metallisation at 24 h has killed the viable bacteria with 97.88% of bactericidal ratio. The Ag was ionised up to 7 days which is crucial to prevent bacterial infection during the first stage of implant restoration. The aged functionalised films were considered stable due to less alteration of its chemical composition, surface roughness and wettability properties. The ability of the functionalised film to coat complex and micro scale metal make it suitable for dental and orthopaedic implants application.