3D-printed biodegradable magnesium alloy scaffolds with zoledronic acid-loaded ceramic composite coating promote osteoporotic bone defect repair.

Osteoporotic fracture is one of the most serious complications of osteoporosis. Most fracture sites have bone defects, and restoring the balance between local osteogenesis and bone destruction is difficult during the repair of osteoporotic bone defects. In this study, we successfully fabricated three-dimensional (3D)-printed biodegradable magnesium alloy (Mg-Nd-Zn-Zr) scaffolds and prepared a zoledronic acid-loaded ceramic composite coating on the surface of the scaffolds. The osteogenic effect of Mg and the osteoclast inhibition effect of zoledronic acid were combined to promote osteoporotic bone defect repair. In vitro degradation and drug release experiments showed that the coating significantly reduced the degradation rate of 3D-printed Mg alloy scaffolds and achieved a slow release of loaded drugs. The degradation products of drug-loaded coating scaffolds can promote osteogenic differentiation of bone marrow mesenchymal stem cells as well as inhibit the formation of osteoclasts and the bone resorption by regulating the expression of related genes. Compared with the uncoated scaffolds, the drug-coated scaffolds degraded at a slower rate, and more new bone grew into these scaffolds. The healing rate and quality of the osteoporotic bone defects significantly improved in the drug-coated scaffold group. This study provides a new method for theoretical research and clinical treatment using functional materials for repairing osteoporotic bone defects.

Additively manufactured biodegradable porous magnesium implants for elimination of implant-related infections: An in vitro and in vivo study.

Magnesium (Mg) alloys that have both antibacterial and osteogenic properties are suitable candidates for orthopedic implants. However, the fabrication of ideal Mg implants suitable for bone repair remains challenging because it requires implants with interconnected pore structures and personalized geometric shapes. In this study, we fabricated a porous 3D-printed Mg-Nd-Zn-Zr (denoted as JDBM) implant with suitable mechanical properties using selective laser melting technology. The 3D-printed JDBM implant exhibited cytocompatibility in MC3T3-E1 and RAW267.4 cells and excellent osteoinductivity in vitro. Furthermore, the implant demonstrated excellent antibacterial ratios of 90.0% and 92.1% for methicillin-resistant S. aureus (MRSA) and Escherichia coli, respectively. The 3D-printed JDBM implant prevented MRSA-induced implant-related infection in a rabbit model and showed good in vivo biocompatibility based on the results of histological evaluation, blood tests, and Mg2+ deposition detection. In addition, enhanced inflammatory response and TNF-α secretion were observed at the bone-implant interface of the 3D-printed JDBM implants during the early implantation stage. The high Mg2+ environment produced by the degradation of 3D-printed JDBM implants could promote M1 phenotype of macrophages (Tnf, iNOS, Ccl3, Ccl4, Ccl5, Cxcl10, and Cxcl2), and enhance the phagocytic ability of macrophages. The enhanced immunoregulatory effect generated by relatively fast Mg2+ release and implant degradation during the early implantation stage is a potential antibacterial mechanism of Mg-based implant. Our findings indicate that 3D-printed porous JDBM implants, having both antibacterial property and osteoinductivity, hold potential for future orthopedic applications.

Fabrication and Biological Activity of 3D-Printed Polycaprolactone/Magnesium Porous Scaffolds for Critical Size Bone Defect Repair.

Polycaprolactone (PCL) is widely used in bone tissue engineering due to its biocompatibility and mechanical strength. However, PCL is not biologically active and shows poor hydrophilicity, making it difficult for new bones to bind tightly to its surface. Magnesium (Mg), an important component of natural bone, exhibits good osteo-inductivity and biological activity. Therefore, porous PCL/Mg scaffolds, including pure PCL, PCL/5%Mg, PCL/10%Mg, and PCL/15%Mg, were prepared to elucidate whether the porous structure of scaffolds and the bioactivity of PCL may be enhanced via 3D printing and incorporation of Mg powder. Compared with the control group (pure PCL only), the hydrophilicity of composite PCL/Mg scaffolds was greatly increased, resulting in the scaffolds having decreased water contact angles. Tests for adhesion and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) indicated that the PCL/10%Mg scaffold showed superior compatibility. Furthermore, as indicated by alkaline phosphatase (ALP) activity and semiquantitative analysis of alizarin red staining, PCL/10%Mg scaffolds exhibited significantly stronger osteogenic activity than the other scaffolds. Animal experiments demonstrated that PCL/10%Mg scaffolds displayed pro-osteogenic effects at an early stage (4 weeks) and produced more new bone mass 8-12 weeks following implantation, compared with the control group. Visceral and blood parameter analyses indicated that PCL/10%Mg scaffolds did not exert any noticeable toxic effects. PCL/10%Mg composite scaffolds were found to promote bone defect repair at an early stage with good cytocompatibility. This finding revealed a new concept in designing bone tissue materials, which showed potential as a clinical treatment for bone defects.

Microstructure, mechanical properties, biocorrosion behavior, and cytotoxicity of as-extruded Mg-Nd-Zn-Zr alloy with different extrusion ratios.

Recently, commercial magnesium (Mg) alloys containing Al (such as AZ31 and AZ91) or Y (such as WE43) have been studied extensively for biomedical applications. However, these Mg alloys were developed as structural materials, not as biomaterials. In this study, a patented Mg-Nd-Zn-Zr (denoted as JDBM) alloy was investigated as a biomedical material. The microstructure, mechanical properties, biocorrosion behavior, and cytotoxicity of the alloy extruded at 320 °C with extrusion ratios of 8 and 25 were studied. The results show that the lower extrusion ratio results in finer grains and higher strength, but lower elongation, while the higher extrusion ratio results in coarser grains and lower strength, but higher elongation. The biocorrosion behavior of the alloy was investigated by hydrogen evolution and mass loss tests in simulated body fluid (SBF). The results show that the alloy extruded with lower extrusion ratio exhibits better corrosion resistance. The corrosion mode of the alloy is uniform corrosion, which is favorable for biomedical applications. Aging treatment on the as-extruded alloy improves the strength and decreases the elongation at room temperature, and has a small positive influence on the corrosion resistance in SBF. The cytotoxicity test indicates that the as-extruded JDBM alloy meets the requirement of cell toxicity.

Effects of extrusion and heat treatment on the mechanical properties and biocorrosion behaviors of a Mg-Nd-Zn-Zr alloy.

Mechanical properties at room temperature and biocorrosion behaviors in simulated body fluid (SBF) at 37 °C of a new type of patented Mg-3Nd-0.2Zn-0.4Zr (hereafter, denoted as JDBM) alloy prepared at different extrusion temperatures, as well as heat treatment, were studied. The mechanical properties of this magnesium alloy at room temperature were improved significantly after extrusion and heat treatment compared to an as-cast alloy. The results of mechanical properties show that the yield strength (YS) decreases with increasing extrusion temperature. The tensile elongation decreases a little while the ultimate tensile strength (UTS) has no obvious difference. The yield strength and ultimate tensile strength were improved clearly after heat treatment at 200 °C for 10 h compared with that at the extrusion state, which can be mainly contributed to the precipitation strengthening. The biocorrosion behaviors of the JDBM alloy were studied using immersion tests and electrochemical tests. The results reveal that the extruded JDBM alloy and the aging treatment on the extruded alloy show much better biocorrosion resistance than that at solid solution state (T4 treatment), and the JDBM exhibited favorable uniform corrosion mode in SBF.