Hyung-Seop Han

Biodegradability engineering of biodegradable Mg alloys: Tailoring the electrochemical properties and microstructure of constituent phases

Crystalline Mg-based alloys with a distinct reduction in hydrogen evolution were prepared through both electrochemical and microstructural engineering of the constituent phases. The addition of Zn to Mg-Ca alloy modified the corrosion potentials of two constituent phases (Mg + Mg2Ca), which prevented the formation of a galvanic circuit and achieved a comparable corrosion rate to high purity Mg. Furthermore, effective grain refinement induced by the extrusion allowed the achievement of much lower corrosion rate than high purity Mg. Animal studies confirmed the large reduction in hydrogen evolution and revealed good tissue compatibility with increased bone deposition around the newly developed Mg alloy implants. Thus, high strength Mg-Ca-Zn alloys with medically acceptable corrosion rate were developed and showed great potential for use in a new generation of biodegradable implants.

Long-term clinical study and multiscale analysis of in vivo biodegradation mechanism of Mg alloy

Significance In the past decade, countless studies have been performed to control the mechanical and corrosion property of magnesium-based alloy, which degrades in the physiological environment, to overcome the flaws of the inert implant materials and shift the paradigm of conventional bone fixation devices. Controlled degradation of Mg-5wt%Ca-1wt%Zn alloy results in the formation of biomimicking calcification matrix at the degrading interface to initiate the bone formation process. This process facilitates early bone healing and allows the complete replacement of biodegradable Mg implant by the new bone within 1 y of implantation, as demonstrated in 53 cases of successful long-term clinical study. There has been a tremendous amount of research in the past decade to optimize the mechanical properties and degradation behavior of the biodegradable Mg alloy for orthopedic implant. Despite the feasibility of degrading implant, the lack of fundamental understanding about biocompatibility and underlying bone formation mechanism is currently limiting the use in clinical applications. Herein, we report the result of long-term clinical study and systematic investigation of bone formation mechanism of the biodegradable Mg-5wt%Ca-1wt%Zn alloy implant through simultaneous observation of changes in element composition and crystallinity within degrading interface at hierarchical levels. Controlled degradation of Mg-5wt%Ca-1wt%Zn alloy results in the formation of biomimicking calcification matrix at the degrading interface to initiate the bone formation process. This process facilitates early bone healing and allows the complete replacement of biodegradable Mg implant by the new bone within 1 y of implantation, as demonstrated in 53 cases of successful long-term clinical study.

Creating Hierarchical Topographies on Fibrous Platforms Using Femtosecond Laser Ablation for Directing Myoblasts Behavior.

Developing an artificial extracellular matrix that closely mimics the native tissue microenvironment is important for use as both a cell culture platform for controlling cell fate and an in vitro model system for investigating the role of the cellular microenvironment. Electrospinning, one of the methods for fabricating structures that mimic the native ECM, is a promising technique for creating fibrous platforms. It is well-known that align or randomly distributed electrospun fibers provide cellular contact guidance in a single pattern. However, native tissues have hierarchical structures, i.e., topographies on the micro- and nanoscales, rather than a single structure. Thus, we fabricated randomly distributed nanofibrous (720 ± 80 nm in diameter) platforms via a conventional electrospinning process, and then we generated microscale grooves using a femtosecond laser ablation process to develop engineered fibrous platforms with patterned hierarchical topographies. The engineered fibrous platforms can regulate cellular adhesive morphology, proliferation, and distinct distribution of focal adhesion proteins. Furthermore, confluent myoblasts cultured on the engineered fibrous platforms revealed that the direction of myotube assembly can be controlled. These results indicate that our engineered fibrous platforms may be useful tools in investigating the roles of nano- and microscale topographies in the communication between cells and ECM.

Facile solvothermal preparation of monodisperse gold nanoparticles and their engineered assembly of ferritin-gold nanoclusters.

Herein, we report a quick and simple synthesis of water-soluble gold nanoparticles using a HAuCl4 and oleylamine mixture. Oleylamine serves as a reduction agent as well as a stabilizer for nanoparticle surfaces. The particle sizes can be adjusted by modulating reaction temperature and time. Solvothermal reduction of HAuCl4 with oleylamine can be confirmed by measuring the product in Fourier transform infrared (FTIR) spectroscopy. The plasmon band shifting from yellow to red confirms a nanosized particle formation. Amide bonds on the surface of the nanoparticles formed hydrogen bonds with one another, resulting in a hydrophobic monolayer. Particles dispersed well in nonpolar organic solvents, such as in hexane or toluene, by brief sonication. Next, we demonstrated the transfer of gold nanoparticles into water by lipid capsulation using 1-myristoyl-2-hydroxy-sn-glycero-3-phosphocholine (MHPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy polyethylene glycol)-2000 (DPPE-PEG2k), and 1,2-dioleoyl-sn-glycero-3-N-{5-amino-1-carboxypentyl}iminodiacetic acid succinyl nickel salt [DGS-NTA(Ni)]. The particle concentration can be obtained using an absorbance in ultraviolet-visible (UV-vis) spectra (at 420 nm). Instrumental analyses using transmission electron microscopy (TEM), energy-dispersive X-ray (EDX) analysis, dynamic light scattering (DLS), and FTIR confirmed successful production of gold nanoparticles and fair solubility in water. Prepared gold particles were selectively clustered via engineered ferritin nanocages that provide multiple conjugation moieties. A total of 5-6 gold nanoparticles were clustered on a single ferritin nanocage confirmed in TEM. Reported solvothermal synthesis and preparation of gold nanoclusters may serve as an efficient, alternate way of preparing water-soluble gold nanoparticles, which can be used in a wide variety of biomedical applications.

The modification of microstructure to improve the biodegradation and mechanical properties of a biodegradable Mg alloy.

The effect of microstructural modification on the degradation behavior and mechanical properties of Mg-5wt%Ca alloy was investigated to tailor the load bearing orthopedic biodegradable implant material. The eutectic Mg/Mg2Ca phase precipitated in the as-cast Mg-5wt%Ca alloy generated a well-connected network of Mg2Ca, which caused drastic corrosion due to a micro galvanic cell formed by its low corrosion potential. Breaking the network structure using an extrusion process remarkably retarded the degradation rate of the extruded Mg-5wt%Ca alloy, which demonstrates that the biocompatibility and mechanical properties of Mg alloys can be enhanced through modification of their microstructure. The results from the in vitro and in vivo study suggest that the tailored microstructure by extrusion impede the deterioration in strength that arises due to the dynamic degradation behavior in body solution.

In vivo corrosion mechanism by elemental interdiffusion of biodegradable Mg–Ca alloy†

We elucidated the in vivo corrosion mechanism of the biodegradable alloy Mg-10 wt % Ca in rat femoral condyle through transmission electron microscope observations assisted by focused ion beam technique. The alloy consists of a primary Mg phase and a three-dimensional lamellar network of Mg and Mg(2)Ca. We found that the Mg(2)Ca is rapidly corroded by interdiffusion of Ca and O, leading to a structural change from lamellar network to nanocrystalline MgO. In contrast to the fast corrosion rate of the lamellar structure, the primary Mg phase slowly changes into nanocrystalline MgO through surface corrosion by O supplied along the lamellar networks. The rapid interdiffusion induces an inhomogeneous Ca distribution and interestingly leads to the formation of a transient CaO phase, which acts as a selective leaching path for Ca. In addition, the outgoing Ca with P from body fluids forms needle-type calcium phosphates similar to hydroxyl apatite at interior and surface of the implant, providing an active biological environment for bone mineralization.

Multifunctional composite coating as a wear-resistant layer for the bearing in total hip joint replacement.

In this study, we developed Ti-TiN composite coatings with fine lamellar structures for use as an enhanced wear-resistant layer between the bearing components of the polymer-lined acetabular cup and the metal femoral head of total hip joint replacements (THRs). A plasma spraying deposition method was used to apply the composite coatings, and the thickness of TiN layer in the composite could be controlled by varying the flow rate of N(2) atmospheric gas. The surface properties, such as roughness and hardness, were analyzed, and the friction coefficient (μ) and wear rate (k) were measured using a bovine serum wear test. A biocompatibility test was performed to evaluate the toxicity of the composite coatings. Our experimental results reveal that the friction and wear resistance of composite coatings is superior to that of the metallic implant materials, and they have a higher level of fracture toughness as compared with other ceramic coatings because of a good balance between the hardness of the TiN and the toughness of the Ti. Furthermore, these coatings possessed excellent biocompatibility. The experimental results also demonstrate that the improved wear properties can be attributed to a certain level of unavoidable porosity that is due to the rapid solidification of liquid droplets during the plasma spraying process. The pores in the coating surface play an important role as a lubricant (bovine serum) reservoir, reducing the actual contact area and friction losses.

Bone formation within the vicinity of biodegradable magnesium alloy implant in a rat femur model

The purposes of this preliminary study were to investigate the effect of increased Ca contents (5–10 wt% Ca) in Mg-Ca alloy on the mechanical properties and osseous healing rate in a standard rat defect model. Mechanical tests were performed using a compression system followed by qualitative histological analysis using the hemotoxylin and eosin (H&E) staining method and quantitative reverse transcriptase polymerase chain reaction (reverse transcriptase PCR). Mg-Ca alloy degraded fast in vivo while displaying a high level of the bone formation markersOC and ALP. Favorablemechanical strength properties were displayed as Ca content increased from 5 wt% to 10 wt% to show its potential to be considered as a load bearing implant material. The resultfrom this study suggests that the developed Mg-Ca alloy has the potential to serve as a biocompatible load bearing implant material that is degradable and possibly osteoconductive.

Load-bearing capacity and biological allowable limit of biodegradable metal based on degradation rate in vivo.

In this study, a newly developed Mg-Ca-Zn alloy for low degradation rate and surface erosion properties was evaluated. The compressive, tensile, and fatigue strength were measured before implantation. The degradation behavior was evaluated by analyzing the microstructure and local hardness of the explanted specimen. Mean and maximum degradation rates were measured using micro CT equipment from 4-, 8-, and 16- week explants, and the alloy was shown to display surface erosion properties. Based on these characteristics, the average and minimum load bearing capacities in tension, compression, and bending modes were calculated. According to the degradation rate and references of recommended dietary intakes (RDI), the Mg-Ca-Zn alloy appears to be safe for human use.

Effect of surface area on corrosion properties of magnesium for biomaterials

This study examined the effect of the surface area on the corrosion properties of magnesium through in vivo (weight loss test) and in vitro (electrochemical and weight loss tests in Hank’s solution) tests. The corrosion rate was reduced as the surface area increased. Surface analysis showed that the precipitation of calcium phosphate increased with increasing surface area. Moreover, the pH level around the specimen increased with increasing surface area. This increase of pH can accelerate the precipitation of calcium phosphate on the surface. However, different mechanism of calcium phosphate precipitation was found for in vivo and vitro test environment. In vitro environment showed an increase of calcium phosphate due to the continuous increase in pH, whereas in vivo environment showed increase of calcium phosphate to maintain homeostasis and reduced the level of pH in physiological system. Consequently, the increase in magnesium surface area leads to increase the precipitation of calcium phosphate as a more stable rust layer which ultimately increases the corrosion resistance of magnesium.