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.biodegradable implant | bone formation | clinical application T he century-old concept of the fixation device that holds the fractured bones in place to allow repair through the natural bone remodeling process is still being practiced today without alteration (1-5). The recent rapid growth of the elderly demographic of physically active adults has tremendously intensified the occurrence of bone trauma cases, highlighting once again the major drawbacks of current surgical approaches and osteosynthesis systems, such as inevitable secondary surgery to remove the inert fixation devices after complete bone healing and inflammatory response due to the release of metal ions. In the past decade, countless studies have been performed to control and optimize the mechanical and corrosion properties of magnesium-based alloys (6-9), which, thanks to their degradation in the physiological environment, could overcome the limitations of inert implant materials and shift the paradigm of conventional bone fixation devices toward new horizons. Driven by these new possibilities, important findings regarding, among others, the degradation mechanism of Mg-based alloys (10, 11), the formation of corrosion protective layers by degradation products (12, 13), and the osteogenetic properties of Mg ions (14, 15) have been reported in the literature. However, such findings are based on the observation of degradation products and of bone healing at the macroscale level. Due to lack of fundamental understanding on biocompatibility and underlying bone formation mechanism of the degradation product, there is so far only one known case of statistically insignificant clinical study result (16) with a short-term follow-up. In our previous study, we reported successful development and long-term in vivo study of uniformly slowly degrading Mg-5wt%Ca-1wt%Zn alloy system (SI Appendix, Figs. S1 and S2) featuring adequate mechanical strength [ultimate tensile strength (UTS) ∼250 MPa] (17) a...
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.
Objective. This study was undertaken to generate and characterize human induced pluripotent stem cells (PSCs) from patients with osteoarthritis (OA) and to examine whether these cells can be developed into disease-relevant cell types for use in disease modeling and drug discovery.
Methods. Human synovial cells isolated from two
Utilization of biodegradable metals in biomedical fields is emerging because it avoids high-risk and uneconomic secondary surgeries for removing implantable devices. Mg and its alloys are considered optimum materials for biodegradable implantable devices because of their high biocompatibility; however, their excessive and uncontrollable biodegradation is a difficult challenge to overcome. Here, we present a novel method of inhibiting Mg biodegradation by utilizing reduced nicotinamide adenine dinucleotide (NADH), an endogenous cofactor present in all living cells. Incorporating NADH significantly increases Mg corrosion resistance by promoting the formation of thick and dense protective layers. The unique mechanism by which NADH enables corrosion inhibition was discovered by combined microscopic and spectroscopic analyses. NADH is initially self-adsorbed onto the surface of Mg oxide layers, preventing Cl− ions from dissolving Mg oxides, and later recruits Ca2+ ions to form stable Ca-P protective layers. Furthermore, stability of NADH as a corrosion inhibitor of Mg under physiological conditions were confirmed using cell tests. Moreover, excellent cell adhesion and viability to Mg treated with NADH shows the feasibility of introduction of NADH to Mg-based implantable system. Our strategy using NADH suggests an interesting new way of delaying the degradation of Mg and demonstrates potential roles for biomolecules in the engineering the biodegradability of metals.
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