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

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.

Biomedical Device Surface Treatment by Laser-Driven Hydroxyapatite Penetration-Synthesis Technique for Gapless PEEK-to-Bone Integration.

Polyetheretherketone (PEEK), a bioinert polymer known for its mechanical properties similar to bone, is capable of averting stress shielding. Due to these attributes, it finds applications in diverse fields like orthopedics, encompassing cervical disc replacement for the neck and spine, along with dentistry and plastic surgery. However, due to insufficient bonding with bone, various methods such as hydroxyapatite (HA) coating on the surface are attempted. Nonetheless, the interface between the polymer and ceramic, two different materials, tended to delaminate after transplantation, posing challenges in preventing implant escape or dislodgement. This research delves into the laser-driven hydroxyapatite penetration-synthesis technique. Differing from conventional coating methods that bond layers of dissimilar materials like HA and PEEK, this technology focuses on synthesizing and infiltrating ionized HA within the PEEK substrate resulting in an interface-free HA-PEEK surface. Conversely, HA-PEEK with this technology applied achieves complete, gap-free direct bone-implant integration.  Our research involved the analysis of various aspects. By means of these, we quantitatively assesed the enhanced bone bonding characteristics of HA-PEEK surfaces treated with this approach and offered and explanation for the mechanism responsible for direct bone integration.

Reduction of magnetic resonance image artifacts of NiTi implant by carbon coating.

A paramagnetic NiTi substrate was coated with diamagnetic carbon materials, i.e., graphene, graphene oxide (GO), and carbon nanotubes (CNTs), in order to reduce magnetic resonance (MR) image artifacts of NiTi implants. The present study focused on the effect of magnetic susceptibility variations in NiTi caused by the carbon coating on MR image artifacts. In the case of the graphene and GO coatings, the reduction of the magnetic susceptibility was greater along the perpendicular direction than the parallel direction. In contrast, the CNT coating exhibited a larger reduction along the parallel direction. The reduction of magnetic susceptibility measured in CNT-coated NiTi (CNT/NiTi) was smaller than the theoretical prediction especially when measured along the parallel direction, because CNTs on the NiTi surface were randomly arranged, rather than in a single direction. MR image artifacts were substantially reduced in all carbon-coated NiTi specimens, which is due to the reduction of magnetic susceptibility in NiTi by the carbon coating. This method can also be applied to other paramagnetic bio-metallic materials such as Co-Cr.

Evaluation of mechanical strength and bone regeneration ability of 3D printed kagome-structure scaffold using rabbit calvarial defect model.

In clinical conditions, the reconstructions performed in the complex and three-dimensional bone defects in the craniomaxillofacial (CMF) area are often limited in facial esthetics and jaw function. Furthermore, to regenerate a bone defect in the CMF area, the used scaffold should have unique features such as different mechanical strength or physical property suitable for complex shape and function of the CMF bones. Therefore, a three-dimensional synthetic scaffold with a patient-customized structure and mechanical properties is more suitable for the regeneration. In this study, the customized kagome-structure scaffold with complex morphology was assessed in vivo. The customized 3D kagome-structure model for the defect region was designed according to data using 3D computed tomography. The kagome-structure scaffold and the conventional grid-structure scaffold (as a control group) were fabricated using a 3D printer with a precision extruding deposition head using poly(ε-caprolactone) (PCL). The two types of 3D printed scaffolds were implanted in the 8-shaped defect model on the rabbit calvarium. To evaluate the osteoconductivity of the implanted scaffolds, new bone formation, hematoxylin and eosin staining, immunohistochemistry, and Masson's trichrome staining were evaluated for 16 weeks after implantation of the scaffolds. To assess the mechanical robustness and stability of the kagome-structure scaffold, numerical analysis considering the 'elastic-perfectly plastic' material properties and deformation under self-contact condition was performed by finite element analysis. As a result, the kagome-structure scaffold fabricated using 3D printing technology showed excellent mechanical robustness and enhanced osteoconductivity than the control group. Therefore, the 3D printed kagome-structure scaffold can be a better option for bone regeneration in complex and large defects than the conventional grid-type 3D printed scaffold.

A new corrosion-inhibiting strategy for biodegradable magnesium: reduced nicotinamide adenine dinucleotide (NADH).

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.

Comprehensive study on the roles of released ions from biodegradable Mg-5 wt% Ca-1 wt% Zn alloy in bone regeneration.

We report here the effect of micro-environmental changes from biodegradable magnesium alloys on the activities of cells - osteoblasts, osteoclasts and macrophages - which play critical roles in each phase of the bone-regeneration process. Despite positive bone formation effects from several in vivo studies, minimal progress has been made in identifying underlying mechanisms through in vitro studies, which are currently concentrated on osteoblastic activities. The observed in vitro and in vivo results indicated that alkaline pH and released magnesium and zinc ions derived from Mg-5 wt% Ca-1 wt% Zn alloy biodegradation promote the progress of bone formation. In contrast, alkaline pH and magnesium ions remarkably suppressed osteoclastic activities and pro-inflammatory cytokine production, closely related to osteolysis and prosthesis failure. Findings from the present study conclude that the degradation of Mg-5 wt% Ca-1 wt% Zn alloys can promote new bone formation by simultaneously affecting the complex combination of variable cellular activities and phases. Copyright © 2016 John Wiley & Sons, Ltd.

Magnesium ions facilitate integrin alpha 2- and alpha 3-mediated proliferation and enhance alkaline phosphatase expression and activity in hBMSCs.

Magnesium metal and its alloys have been proposed as a novel class of bone implant biomaterials because of their biodegradability and mechanical properties. The purpose of this study was to determine whether magnesium ions, which are released abundantly from alloys, affect proliferation and differentiation of human bone marrow-derived stromal cells (hBMSCs). High levels of magnesium ions did not induce cytotoxicity in hBMSCs, but treatment with 2.5-10 mm magnesium ions for 48-72 h significantly increased hBMSC proliferation. The expression of integrins α2 and α3, but not ß1, was upregulated compared with the control and shifted from α3 to α2 in hBMSCs treated with magnesium ions. Knockdown of integrins α2 and/or α3 significantly reduced magnesium-induced proliferation of hBMSCs. Magnesium exposure profoundly enhanced alkaline phosphatase (ALP) gene expression and activity even at a relatively low magnesium concentration (2.5 mm). Exposure to magnesium ions facilitated hBMSC proliferation via integrin α2 and α3 expression and partly promoted differentiation into osteoblasts via the alteration of ALP expression and activity. Accordingly, magnesium could be a useful biomaterial for orthopaedic applications such as bone implant biomaterials for repair and regeneration of bone defects in orthopaedic and dental fields. Copyright © 2014 John Wiley & Sons, Ltd.

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.