Bioactive Ca-P coating with self-sealing structure on pure magnesium.

Bioactive coatings containing Ca and P with self-sealing structures were fabricated on the surface of pure magnesium using micro-arc oxidation technique (MAO) in a specific calcium hydroxide based electrolyte system. Coatings were prepared at three applied voltages, i.e. 360, 410 and 450 V, and the morphology, chemical composition, corrosion resistance and the degradation properties in Hank's solution of the MAO-coated samples with three different applied voltages were investigated. It was found that all the three coatings showed similar surface morphologies that the majority of micro-pores were filled with compound particles. Both the porous structures and the compound particles were found to contain consistent chemical compositions which were mainly composed of O, Mg, F, Ca and P. Electrochemical tests showed a significant increase in corrosion resistance for the three coatings, meanwhile the coating obtained at 450 V exhibited the superior corrosion resistance owing to the largest coating thickness. The long term immersion tests in Hank's solution also revealed an effective reduction in corrosion rate for the MAO coated samples, and the pH values of the coated samples always maintained a lower level. Besides, all the three coatings were subjected to a mild and uniform degradation, while the coating obtained at 360 V showed a relatively obvious degradation characteristic and appreciable Ca and P contents on the surfaces of the three coatings were observed after immersion in Hank's solution. The results of the present study confirmed that the MAO coatings containing bioactive Ca and P elements with self-sealing structures could significantly enhance the corrosion resistance of magnesium substrate in Hanks' solution with great potential for medical application.

High-purity weight-bearing magnesium screw: Translational application in the healing of femoral neck fracture.

Magnesium (Mg)-based metals can be used as next-generation fracture internal fixation devices due to their specific properties. We used vascularized bone grafting fixed by degradable pure Mg screws and obtained satisfactory results in the treatment of osteonecrosis of the femoral head. However, the mechanical properties of these screws make them weaker than those made of traditional metals. In particular, one of the main challenges of using screws made of Mg-based metals is their application in fixation at important weight-bearing sites in the human body. Femoral neck fracture is a common clinical injury. In this injury, the large bearing stress at the junction requires a fixation device with extremely high mechanical strength. Surgery and appropriate internal fixation can accelerate the healing of femoral neck fractures. Traditional internal fixation devices have some disadvantages after surgery, including stress shielding effects and the need for secondary surgery to remove screws. On the basis of previous work, we developed high-strength pure Mg screws for femoral neck fractures. In this study, we describe the first use of high-purity Mg to prepare large-size weight-bearing screws for the fixation of femoral neck fractures in goats. We then performed a 48 weeks follow-up study using in vivo transformation experiments. The results show that these biodegradable high-purity Mg weight-bearing screws had sufficient mechanical strength and a degradation rate compatible with bone repair. Furthermore, good bone formation was achieved during the degradation process and reconstruction of the bone tissue and blood supply of the femoral head and femoral neck. This study provides a basis for future research on the clinical transformation of biodegradable high-purity Mg weight-bearing screws.

Study on a biodegradable antibacterial Fe-Mn-C-Cu alloy as urinary implant material.

Biodegradable Fe based alloys have been investigated for fracture fixation and cardiovascular support to overcome complications of permanent implants. This study was focused on the development of a new Fe-Mn-C-Cu alloy with antibacterial and anti-encrustation properties as a urinary implant material. The microstructure and mechanical properties of the alloy were studied. The degradation behavior, antibacterial and anti-encrustation properties were evaluated by immersion test, antibacterial test and encrustation test, respectively. The results showed that Fe-Mn-C-Cu alloy was a non-magnetic, biodegradable, anti-bacterial and anti-encrustation alloy that could inhibit the biofilm and stone formations on its surface through the dual effects of degradation and Cu ions release. The study revealed the preliminary mechanisms of anti-infection and anti-encrustation for Fe-Mn-C-Cu alloy due to the continuous release of Cu2+ ions, which provides a new idea for application of biodegradable Fe-based material and the treatment of urinary tract infections and stones in the urinary system.

Template-assisted, Sol-gel Fabrication of Biocompatible, Hierarchically Porous Hydroxyapatite Scaffolds.

Hierarchically porous hydroxyapatite (HHA) scaffolds were synthesized by template-assisted sol-gel chemistry. Polyurethane foam and a block copolymer were used as templates for inducing hierarchically porous structures. The HHA scaffolds exhibited open porous structures with large pores of 400-600 µm and nanoscale pores of ~75 nm. In comparison with conventional hydroxyapatite (CHA), HHA scaffolds exhibited significantly higher surface areas and increased protein adsorption for bovine serum albumin and vitronectin. Both the HHA and CHA scaffolds exhibited well in vitro biocompatibility. After 1 day, Saos-2 osteoblast-like cells bound equally well to both HHA and CHA scaffolds, but after 7 days in culture, cell proliferation was significantly greater on the HHA scaffolds (p < 0.01). High surface area and hierarchical porous structure contributed to the selective enhancement of osteoblast proliferation on the HHA scaffolds.

Biomechanical comparison of pure magnesium interference screw and polylactic acid polymer interference screw in anterior cruciate ligament reconstruction-A cadaveric experimental study.

BACKGROUND: Polylactic acid polymer interference screws are commonly used in anterior cruciate ligament (ACL) reconstructions, especially in proximal tibia fixation. However, several concerns have been raised, including the acid products during its degradation in vivo. In recent years, biodegradable magnesium (Mg)-based implants have become attractive because of their favourable mechanical properties, which are more similar to those of natural bone when compared with other degradable materials, such as polymers, apart from their alkaline nature during degradation. METHODS: We developed a pure Mg interference screw for ACL reconstruction. In the present study, 24 fresh cadaver knees were used to compare the mechanical properties of pure Mg interference screws and polylactic acid polymer interference screws for ACL reconstruction via their application on the proximal tibia tested using specific robotics. RESULTS: Results showed that the pure Mg interference screw group showed similar mechanical stability to the polylactic acid polymer interference screw group, implying comparable postoperative fixation effects. CONCLUSION: As there are no commercially available Mg-based interference screws for ACL reconstruction clinically and the in vivo degradation of pure Mg promotes bone formation, our cadaveric study supports its clinical tests for ACL reconstruction.

Biodegradable Magnesium (Mg) Implantation Does Not Impose Related Metabolic Disorders in Rats with Chronic Renal Failure.

Mg and its alloys have been considered as one of the most promising biodegradable medical devices, but it was still unclear whether hypermagnesemia involved health risks would occur in persons with kidney disease due to their deteriorated kidney function for Mg ions excretion from their body. In this study, we established a chronic renal failure (CRF) model in rats induced by adenine administration prior to Mg implantation, aiming to predict if CRF patients are suitable for the use of Mg implants. The results showed that Mg levels in serum, urine, feces and internal organs had no significant changes after Mg implantation for both normal and CRF rats. Biochemical indices detection and histopathological analysis in kidney, liver and heart tissue confirmed that Mg implants did not induce any extra damage in animals even with renal failure. Our study indicates that Mg based orthopaedic medical device may be considered for use in CRF patients without biosafety concerns.

Vascularized bone grafting fixed by biodegradable magnesium screw for treating osteonecrosis of the femoral head.

Hip-preserving surgery with vascularized bone graft implantation has been widely practiced in treating osteonecrosis of the femoral head (ONFH). However, the current approach presents a drawback, in which the implanted bone graft without screw fixation may slip or exhibit a certain degree of displacement postoperatively. This study was designed to investigate the application potential of biodegradable magnesium (Mg) screws for the fixation of vascularized bone graft in ONFH patients. Forty-eight patients were randomly divided into two groups: the Mg screw group (vascularized bone grafting fixed by Mg screws) and the control group (vascularized bone grafting without fixation). During 12 month follow-up period after surgery, treatment outcomes in patients were assessed by multiple imaging techniques including x-ray and computed tomography (CT) scanning as well as functional recovery Harris hip score (HHS). The temporal changes in serum levels of Mg, Ca, and P as well as in vivo degradation rate of Mg screws were determined. The absence of potential adverse effects induced by degradation products from Mg screws on surrounding bone tissue was validated via CT imaging analysis. HHS was significantly improved in the Mg screw group when compared to the control group. X-ray imaging analysis showed that the screw shape did not show significant alteration due to the diameter of Mg screws measured with approximate 25% reduction within 12 months post-surgically. The postoperative serum levels of Ca, Mg, and P, which are relevant for liver and kidney function, were all within normal physiological range in all patients of both groups. The use of biodegradable Mg screws may provide a promising bone graft-screw fixation route in treating ONFH and present considerable potential for orthopedic applications.

Recommendation for modifying current cytotoxicity testing standards for biodegradable magnesium-based materials.

As one of the most promising medical metal implants, magnesium (Mg) or its alloys have shown significant advantages over other candidates attributed to not only their excellent biodegradability and suitable mechanical properties but also their osteopromotive effects for bone applications. Prior to approval mandated by the governmental regulatory body, the access to the medical market for Mg-based implants requires a series of testing for assurance of their safety and efficacy via preclinical evaluations and clinical tests including phase 1 and 2 evaluations, and phase 3 of multi-center randomized double blind and placebo-controlled clinical trials. However, as the most widely used protocols for biosafety evaluation of medical devices, current ISO 10993 standards should be carefully reevaluated when directly applying them to predict potential health risks of degradable Mg based biomaterials via cytotoxicity tests due to the huge gap between in vitro and in vivo conditions. Therefore, instead of a direct adoption, modification of current ISO standards for in vitro cytotoxicity test is desirable and justified. The differences in sensitivities of cells to in vitro and in vivo Mg ions and the capability of in vivo circulation system to dilute local degradation products were fully considered to propose modification of current ISO standards. This paper recommended a minimal 6 times to a maximal 10 times dilution of extracts for in vitro cytotoxicity test specified in ISO 10993 part 5 for pure Mg developed as potential orthopedic implants based on literature review and our specifically designed in vitro and in vivo tests presented in the study. Our work may contribute to the progress of biodegradable metals involved translational work.

Microstructure, mechanical properties, in vitro degradation and cytotoxicity evaluations of Mg-1.5Y-1.2Zn-0.44Zr alloys for biodegradable metallic implants.

Mg-1.5Y-1.2Zn-0.44Zr alloys were newly developed as degradable metallic biomaterials. A comprehensive investigation of the microstructure, mechanical properties, in vitro degradation assessments and in vitro cytotoxicity evaluations of the as-cast state, as-heat treated state and as-extruded state alloys was done. The microstructure observations show that the Mg-1.5Y-1.2Zn-0.44Zr alloys are mainly composed of the matrix α-Mg phases and the Mg12ZnY secondary phases (LPS structure). The hot extrusion method significantly refined the grains and eliminated the defects of both as-cast and heat treated alloys and thereby contributed to the better mechanical properties and biodegradation resistance. The values of tensile strength and tensile yield strength of the alloy in the as-extruded condition are about 236 and 178 MPa respectively, with an excellent elongation of 28%. Meanwhile, the value of compressive strength is about 471 MPa and the value of bending strength is about 501 MPa. The superior bending strength further demonstrates the excellent ductility of the hot extruded alloys. The results of immersion tests and electrochemical measurements in the SBF indicate that a protective film precipitated on the alloy's surface with the extension of degradation. The protective film contains Mg(OH)2 and hydroxyapatite (HA) which can reinforce osteoblast activity and promote good biocompatibility. No significant cytotoxicity towards L-929 cells was detected and the immersion extracts of alloy samples could enhance the cell proliferation with time in the cytotoxicity evaluations, implying that the Mg-1.5Y-1.2Zn-0.44Zr alloys have the potential to be used for biomedical applications.

Cytotoxicity studies of AZ31D alloy and the effects of carbon dioxide on its biodegradation behavior in vitro.

Magnesium alloys have been advocated as potential artificial bone materials due to their biocompatibility and biodegradability. The understanding of their corrosive mechanism in physiological environments is therefore essential for making application-orientated designs. Thus, this in vitro study was designed to assess the effects of CO2 on corrosive behavior of AZ31D to mimic in vivo special ingredient. Electrochemical technologies accompanied with Scanning electron microscope, Fourier transform infrared, X-ray diffraction, Energy dispersive spectroscopy and hydrogen evolution measurement were employed to analyze corrosive rates and mechanisms of AZ31D. Moreover, the biocompatibility of AZ31D was assessed with a direct cell attachment assay and an indirect cytotoxicity test in different diluted extracts. The ion concentrations in extracts were measured using inductively coupled plasma mass spectrometry to offer explanations on the differences of cell viability in the indirect test. The results of the direct cytotoxicity assay showed that the corrosive rate of AZ31D was too rapid to allow for cell adhesion. Extracts diluted less than 20 times would cause adverse effects on cell proliferation, likely due to excessive ions and gas release. Moreover, the presence of CO2 did not cause significant differences on corrosive behavior of AZ31D according to the results of electrochemical testing and hydrogen evolution measurement. This might be caused by the simultaneous process of precipitation and dissolution of MgCO3 due to the penetration role of CO2. This analysis of corrosive atmospheres on the degradation behavior of magnesium alloys would contribute to the design of more scientific in vitro testing systems in the future.

Surface modification of magnesium alloys developed for bioabsorbable orthopedic implants: a general review.

As a bioabsorbable metal with mechanical properties close to bone, pure magnesium or its alloys have great potential to be developed as medical implants for clinical applications. However, great efforts should be made to avoid its fast degradation in vivo for orthopedic applications when used for fracture fixation. Therefore, how to decease degradation rate of pure magnesium or its alloys is one of the focuses in Research and Development (R&D) of medical implants. It has been recognized that surface modification is an effective method to prevent its initial degradation in vivo to maintain its desired mechanical strength. This article reviews the recent progress in surface modifications for prevention of fast degradation of magnesium or its alloys using in vitro testing model, a fast yet relevant model before moving towards time-consuming and expensive in vivo testing. Pros and cons of various surface modifications are also discussed for the goal to design available products to be applied in clinical trials.