Biodegradable stents are considered to be a recent innovation, and their feasibility and applicability have been proven in recent years. Research in this area has focused on materials development and biological studies, rather than on how to transform the developed biodegradable materials into the stent itself. Currently available stent technology, the laser cutting-based process, might be adapted to fabricate biodegradable stents. In this work, the fabrication, characterization and testing of biodegradable Fe-Mn stents are described. A standard process for fabricating and testing stainless steel 316L stents was referred to. The influence of process parameters on the physical, metallurgical and mechanical properties of the stents, and the quality of the produced stents, were investigated. It was found that some steps of the standard process such as laser cutting can be directly applied, but changes to parameters are needed for annealing, and alternatives are needed to replace electropolishing.
In-depth analyses of post-corrosion mechanical properties and architecture of open cell iron foams with hollow struts as absorbable bone scaffolds were carried out. Variations in the architectural features of the foams after 14 days of immersion in a Hanks' solution were investigated using micro-computed tomography and scanning electron microscope images. Finite element Kelvin foam model was developed, and the numerical modeling and experimental results were compared against each other. It was observed that the iron foam samples were mostly corroded in the periphery regions. Except for quasi-elastic gradient, other mechanical properties (i.e. compressive strength, yield strength and energy absorbability) decreased monotonically with immersion time. Presence of adherent corrosion products enhanced the load-bearing capacity of the open cell iron foams at small strains. The finite element prediction for the quasi-elastic response of the 14-day corroded foam was in an agreement with the experimental results. This study highlights the importance of considering corrosion mechanism when designing absorbable scaffolds; this is indispensable to offer desirable mechanical properties in porous materials during degradation in a biological environment.
This article reports a degradation study that was done on stent prototypes made of biodegradable Fe35Mn alloy in a simulated human coronary arterial condition. The stent degradation was observed for a short-term period from 0.5 to 168 h, which simulates the early period of stenting procedure. Potentiodynamic polarization and electrochemical impedance spectroscopy were used to quantify degradation rate and surface property of the stents. Results showed that signs of degradation were visible on both crimped and expanded stents after 1 h of test, mostly located on the stent's curvatures. The degradation rate of stent was higher compared to that of the original alloy, indicating the surface altering effect of stent fabrication processing to degradation. A single oxide layer was formed and detected as a porous structure with capacitive behavior. Expanded stents exhibited lower polarization resistance compared to the nonexpanded ones, indicating the cold work effect of expansion procedure to degradation.
This paper discusses the successful fabrication of a novel triple-layered poly(lactic-co-glycolic acid) (PLGA)-based composite membrane using only a single step that combines the techniques of solvent casting and thermally induced phase separation/solvent leaching. The resulting graded membrane consists of a small pore size layer-1 containing 10 wt% non-stoichiometric nanoapatite (NAp)+1-3 wt% lauric acid (LA) for fibroblastic cell and bacterial inhibition, an intermediate layer-2 with 20-50 wt% NAp+1 wt% LA, and a large pore size layer-3 containing 30-100 wt% NAp without LA to allow bone cell growth. The synergic effects of 10-30 wt% NAp and 1 wt% LA in the membrane demonstrated higher tensile strength (0.61 MPa) and a more elastic behavior (16.1% elongation at break) in 3 wt% LA added membrane compared with the pure PLGA (0.49 MPa, 9.1%). The addition of LA resulted in a remarkable plasticizing effect on PLGA at 3 wt% due to weak intermolecular interactions in PLGA. The pure and composite PLGA membranes had good cell viability toward human skin fibroblast, regardless of LA and NAp contents.
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.
Hydroxyapatite (HAp) is an attractive bioceramics due to its similar composition to bone mineral and its ability to promote bone-implant interaction. However, its low strength has limited its application as load bearing implants. This paper presented a work focusing on the improvement of HAp mechanical property by synthesizing iron (Fe)-reinforced bovine HAp nanocomposite powders via mechanosynthesis method. The synthesis process was performed using high energy milling at varied milling time (3, 6, 9, and 12h). The samples were characterized by X-ray diffraction (XRD), Fourier transform infrared (FT-IR), and scanning electron microscopy (SEM). Its mechanical properties were investigated by micro-Vicker's hardness and compression tests. Results showed that milling time directly influenced the characteristics of the nanocomposite powders. Amorphous BHAp was formed after 9 and 12h milling in the presence of HPO4(2-) ions. Continuous milling has improved the crystallinity of Fe without changing the HAp lattice structure. The nanocomposite powders were found in spherical shape, agglomerated and dense after longer milling time. The hardness and Young's modulus of the nanocomposites were also increased at 69% and 66%, respectively, as the milling time was prolonged from 3 to 12h. Therefore, the improvement of the mechanical properties of nanocomposite was attributed to high Fe crystallinity and homogenous, dense structure produced by mechanosynthesis.
A guided bone regeneration (GBR) membrane has been extensively used in the repair and regeneration of damaged periodontal tissues. One of the main challenges of GBR restoration is bacterial colonization on the membrane, constitutes to premature membrane degradation. Therefore, the purpose of this study was to investigate the antibacterial efficacy of triple-layered GBR membrane composed of poly(lactic-co-glycolic acid) (PLGA), nanoapatite (NAp) and lauric acid (LA) with two types of Gram-negative periodontal bacteria, Fusobacterium nucleatum and Porphyromonas gingivalis through a disc diffusion and bacterial count tests. The membranes exhibited a pattern of growth inhibition and killing effect against both bacteria. The increase in LA concentration tended to increase the bactericidal activities which indicated by higher diameter of inhibition zone and higher antibacterial percentage. It is shown that the incorporation of LA into the GBR membrane has retarded the growth and proliferation of Gram-negative periodontal bacteria for the treatment of periodontal disease.
This article describes the development of a partially degradable metal bone pin, proposed to minimize the occurrence of bone refracture by avoiding the creation of holes in the bone after pin removal procedure. The pin was made by friction welding and composed of two parts: the degradable part that remains in the bone and the nondegradable part that will be removed as usual. Rods of stainless steel 316L (nondegradable) and pure iron (degradable) were friction welded at the optimum parameters: forging pressure = 33.2 kPa, friction time = 25 s, burn-off length = 15 mm, and heat input = 4.58 J/s. The optimum tensile strength and elongation was registered at 666 MPa and 13%, respectively. A spiral defect formation was identified as the cause for the ductile fracture of the weld joint. A 40-µm wide intermetallic zone was identified along the fusion line having a distinct composition of Cr, Ni, and Mo. The corrosion rate of the pin gradually decreased from the undeformed zone of pure iron to the undeformed zone of stainless steel 316L. All metallurgical zones of the pin showed no toxic effect toward normal human osteoblast cells, confirming the ppb level of released Cr and Ni detected in the cell media were tolerable.
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 alloy's 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.
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.
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.
Chlorhexidine (CHX) is known for its high antibacterial substantivity and is suitable for use to bio-inert medical devices due to its long-term antibacterial efficacy. However, CHX molecules require a crosslinking film to be stably immobilized on bio-inert metal surfaces. Therefore, polydopamine (PDA) was utilized in this study to immobilize CHX on the surface of 316L type stainless steel (SS316L). The SS316L disks were pre-treated, modified with PDA film and immobilized with different concentrations of CHX (10mM-50mM). The disks were then subjected to various surface characterization analyses (ATR-FTIR, XPS, ToF-SIMS, SEM and contact angle measurement) and tested for their cytocompatibility with human skin fibroblast (HSF) cells and antibacterial activity against Escherichia coli and Staphylococcus aureus. The results demonstrated the formation of a thin PDA film on the SS316L surface, which acted as a crosslinking medium between the metal and CHX. CHX was immobilized via a reduction process that covalently linked the CHX molecules with the functional group of PDA. The immobilization of CHX increased the hydrophobicity of the disk surfaces. Despite this property, a low concentration of CHX optimized the viability of HSF cells without disrupting the morphology of adherent cells. The immobilized disks also demonstrated high antibacterial efficacy against both bacteria, even at a low concentration of CHX. This study demonstrates a strong beneficial effect of the crosslinked PDA film in immobilizing CHX on bio-inert metal, and these materials are applicable in medical devices. Specifically, the coating will restrain bacterial proliferation without suffocating nearby tissues.
This article reports the in vitro degradation and cytotoxicity assessment of Zn-3Mg alloy developed for biodegradable bone implants. The alloy was prepared using casting, and its microstructure was composed of Mg2Zn11 intermetallic phase distributed within a Zn-rich matrix. The degradation assessment was done using potentiodynamic polarization and electrochemical impedance spectrometry. The cell viability and the function of normal human osteoblast cells were assessed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and alkaline phosphatase extracellular enzyme activity assays. The results showed that the degradation rate of the alloy was slower than those of pure Zn and pure Mg due to the formation of a high polarization resistance oxide film. The alloy was cytocompatible with the normal human osteoblast cells at low concentrations (<0.5 mg/mL), and its alkaline phosphatase activity was superior to pure Mg. This assessment suggests that Zn-3Mg alloy has the potential to be developed as a material for biodegradable bone implants, but the toxicity limit must be carefully observed.
Iron and its alloy have been proposed as biodegradable metals for temporary medical implants. However, the formation of iron oxide and iron phosphate on their surface slows down their degradation kinetics in both in vitro and in vivo scenarios. This work presents new approach to tailor degradation behavior of iron by incorporating biodegradable polymers into the metal. Porous pure iron (PPI) was vacuum infiltrated by poly(lactic-co-glycolic acid) (PLGA) to form fully dense PLGA-infiltrated porous iron (PIPI) and dip coated into the PLGA to form partially dense PLGA-coated porous iron (PCPI). Results showed that compressive strength and toughness of the PIPI and PCPI were higher compared to PPI. A strong interfacial interaction was developed between the PLGA layer and the iron surface. Degradation rate of PIPI and PCPI was higher than that of PPI due to the effect of PLGA hydrolysis. The fast degradation of PIPI did not affect the viability of human fibroblast cells. Finally, this work discusses a degradation mechanism for PIPI and the effect of PLGA incorporation in accelerating the degradation of iron.
Active ingredients of ginsenoside, Rg1 and Re, are able to inhibit the proliferation of vascular smooth muscle cells and promote the growth of vascular endothelial cells. These capabilities are of interest for developing a novel drug-eluting stent to potentially solve the current problem of late-stent thrombosis and poor endotheliazation. Therefore, this study was aimed to incorporate ginsenoside into degradable coating of poly(lactic-co-glycolic acid) (PLGA). Drug mixture composed of ginseng extract and 10% to 50% of PLGA (xPLGA/g) was coated on electropolished stainless steel 316L substrate by using a dip coating technique. The coating was characterized principally by using attenuated total reflectance-Fourier transform infrared spectroscopy, scanning electron microscopy and contact angle analysis, while the drug release profile of ginsenosides Rg1 and Re was determined by using mass spectrometry at a one month immersion period. Full and homogenous coating coverage with acceptable wettability was found on the 30PLGA/g specimen. All specimens underwent initial burst release dependent on their composition. The 30PLGA/g and 50PLGA/g specimens demonstrated a controlled drug release profile having a combination of diffusion- and swelling-controlled mechanisms of PLGA. The study suggests that the 30PLGA/g coated specimen expresses an optimum composition which is seen as practicable for developing a controlled release drug-eluting stent.
Iron-bioceramic composites have been developed as biodegradable implant materials with tailored degradation behavior and bioactive features. In the current work, in vivo bioactivity of the composites was comprehensively studied by using sheep animal model. Five groups of specimens (Fe-HA, Fe-TCP, Fe-BCP composites, and pure-Fe and SS316L as controls) were surgically implanted into medio proximal region of the radial bones. Real-time ultrasound analysis showed a decreased echo pattern at the peri-implant biodegradation site of the composites indicating minimal tissue response during the wound healing process. Peripheral whole blood biomarkers monitoring showed a normal dynamic change of blood cellular responses and no stress effect was observed. Meanwhile, the released Fe ion concentration was increasing along the implantation period. Histological analysis showed that the composites corresponded with a lower inflammatory giant cell count than that of SS316L. Analysis of the retrieved implants showed a thicker degradation layer on the composites compared with pure-Fe. It can be concluded that the iron-bioceramic composites are bioactive and induce a preferable wound healing process.