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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.

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.

Bone graft materials are commonly used to regenerate various bone defects, but their application is often limited because of the complex defect shape in various clinical conditions. Hence, customized bone grafts using three-dimensional (3D) printing techniques have been developed. However, conventional simple bone defect models are limited for evaluating the benefits and manufacturing accuracy of 3D-printed customized bone grafts. Thus, the aim of the present study was to develop a complex-shaped bone defect model. We designed an 8-shaped bony defect that consists of two simple circles attached to the rabbit calvarium. To determine the critical-sized defect (CSD) of the 8-shaped defects, 5.6- and 7-mm-diameter trephine burs were tested, and the 7-mm-diameter bur could successfully create a CSD, which was easily reproducible on the rabbit calvarium. The rate of new bone formation was 28.65% ± 8.63% at 16 weeks following creation of the defect. To confirm its efficacy for clinical use, the 8-shaped defect was created on a rabbit calvarium and 3D computed tomography (CT) was performed. A stereolithography file was produced using the CT data, and a 3D-printed polycaprolactone graft was fabricated. Using our 8-shaped defect model, we were able to modify the tolerances of the bone graft and calvarial defect to fabricate a more precise bone graft. Customized characteristics of the bone graft were then used to improve the accuracy of the bone graft. In addition, we confirmed the fitting ability of the 3D-printed graft during implantation of the graft. Our 8-shaped defect model on the rabbit calvarium using a 7.0-mm trephine bur may be a useful CSD model for evaluating 3D-printed graft materials.

Bioengineered skin substitute offers new opportunities for treating various skin ailments. To compensate the structural integrity problems of scaffolds prepared from natural components, we mechanically developed highly modified electrospun nanofibrous membranes, incorporating poly(l-lactide-co-e-caprolactone) (PLCL) into gelatin [poly(l-lactide-co-e-caprolactone)/ gelatin membrane, (P/G (3/7)]. Subsequent to our previous in vitro study, our goal was to evaluate the in vivo performance of PLCL, gelatin, and P/G (3/7) membranes, and investigate the feasibility of the newly developed P/G (3/7) membrane for wound healing. Histological analysis using the mathematical model of wound healing and contraction, revealed the association between stiffness of skin substitute with cytokeratin production and wound contraction rate, and the defect site covered with the stiffer membrane showed lower cytokeratin production, and inversely, higher wound contraction rate. Overall, the P/G (3/7) membrane induced a satisfactory wound healing outcome. However, lower cytokeratin production rate with the mechanically modified P/G membrane involves the importance of the conditional blending of PLCL. Conversely, the condition of PLCL showed some incompatibility and hindrance of skin regeneration, consistent with previous in vitro results. With proper mechanical strength and cell viability, the P/G (3/7) membrane could successfully be used as a suitable skin substitute scaffold.

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.

Biodegradable metallic materials represent a potential step‐change technology that may revolutionize the treatment of broken bones. Implants made with biodegradable metals are significantly stronger than their polymer counterparts and fully biodegradable in vivo, removing the need for secondary surgery or long‐term complications. Here, it is shown how clinically approved Mg alloy promotes improved bone repair using an integrated state of the art fetal mouse metatarsal assay coupled with in vivo preclinical studies, second harmonic generation, secretome array analysis, perfusion bioreactor, and high‐resolution 3D confocal imaging of vasculature within skeletal tissue, to reveal a vascular‐mediated pro‐osteogenic mechanism controlling enhanced tissue regeneration. The optimized mechanical properties and corrosion rate of the Mg alloy lead to a controlled release of metallic Mg, Ca, and Zn ions at a rate that facilitates both angiogenesis and coupled osteogenesis for better bone healing, without causing adverse effects at the implantation site. The findings from this study support ongoing development and refinement of biodegradable metal systems to act as crucial portal technologies with significant potential to improve many clinical applications., An integrated state‐of‐the‐art in vivo and in vitro approach reveals clinically approved Mg5Ca1Zn samples stimulate accelerated bone healing by releasing anabolic metallic ions into the surrounding tissues to enhance the growth of type H blood vessels, which localize at active sites of bone remodeling and actively recruit Osterix‐positive osteoprogenitors to the degrading implant site.

In the present study, the osseointegration of additively manufactured screws with a micro-rough surface structure and conventionally machined Ti6Al4V ELI screws with a smooth surface structure is compared. Screws were implanted in rabbit femurs or tibiae for two weeks. The additively manufactured screws exhibited a micro-rough surface with attached semi-molten powder with a size of 50–100 μm and blunt threads, whereas the conventionally machined screws showed a smooth surface and sharp threads. The bonding strength of the additively manufactured screws was significantly higher than that of the conventionally machined screws. The additively manufactured screws showed higher bone-to-implant contact than the conventionally machined screws. Considerable amount of bone tissue on the surface of the additively manufactured screws remained after the push-out tests, and the rabbit tibiae with the additively manufactured screws were significantly damaged, indicating a higher osseointegration rate. Active osteogenesis was observed around the semi-molten powder of the additively manufactured screws, and new bone was well developed along the micro-rough surface. Overall, this study shows that the micro-rough surface improved the bone ingrowth and suggests that additively manufactured screws may be an alternative to conventionally machined screws.

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(e-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.

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.

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 β1, 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.