RESUMO
Biodegradable Zn alloys have significant application potential for hard-tissue implantation devices owing to their suitable degradation behavior and favorable biocompatibility. Nonetheless, pure Zn and its alloys in the as-cast state are mechanically instable and low in strength, which restricts their clinical applicability. Here, we report the exceptional mechanical, corrosion, and biocompatibility properties of hot-extruded Zn-5RE (wt.%, RE = rare earth of Y; or Ho; or Er) alloys intended for use in biodegradable bone substitutes. The microstructural characteristics, mechanical behavior, corrosion resistance, cytocompatibility, osteogenic differentiation, and capacity of osteogenesis in vivo of the Zn-5RE alloys are comparatively investigated. The Zn-5Y alloy demonstrates the best tensile properties, encompassing a 138 MPa tensile yield strength, a 302 MPa ultimate tensile strength, and 63% elongation, while the Zn-5Ho alloy shows the highest compression yield strength of 260 MPa and Vickers hardness of 104 HV. The Zn-5Er alloy shows a 126 MPa tensile yield strength, a 279 MPa ultimate tensile strength, 52% elongation, a 196 MPa compression yield strength, and a 101 HV Vickers microhardness. Further, the Zn-5Er alloy has a 130 µm per year corrosion rate in electrochemical tests and a 26 µm per year degradation rate in immersion tests, which is the lowest among the tested alloys. It also has the best in vitro osteogenic differentiation ability and capacity for osteogenesis and osteointegration in vivo after implantation in rat femurs among the Zn-5RE alloys, indicating promising potential in load-bearing biodegradable internal bone-fixation applications. STATEMENT OF SIGNIFICANCE: This work reports the exceptional mechanical, corrosion, and biocompatibility properties of hot-extruded (HE) Zn-5 wt.%-rare earth (Zn-5RE) alloys using single yttrium (Y), holmium (Ho), and erbium (Er) alloying for biodegradable bone-implant applications. Our findings demonstrate that the HE Zn-5Er alloy showed σuts of 279 MPa, tensile yield strength of 126 MPa, elongation of 51.6%, compression yield strength of 196 MPa, and microhardness of 101.2 HV. Further, HE Zn-5Er showed the lowest electrochemical corrosion rate of 130 µm/y and lowest degradation rate of 26 µm/y, and the highest in vitro osteogenic differentiation ability, in vivo osteogenesis, and osteointegration ability after implantation in rat femurs among the Zn-5RE alloys, indicating promising potential in load-bearing biodegradable internal bone-fixation applications.
RESUMO
Periodontitis, the second most common oral disease, is primarily initiated by inflammatory responses and osteoclast differentiation, in which the MAPK signaling pathway and mitochondrial function play important roles. 3-methyl-1H-indol-1-yl dimethylcarbamodithioate (3o), a hybrid of indole and dithiocarbamate, was first synthesized by our group. It has shown anti-inflammatory activity against lipopolysaccharide-induced acute lung injury. However, it is not known if 3o can exert effects in periodontitis. In vitro study: LPS-induced macrophage inflammation initiation and a receptor activator of nuclear factor κB ligand-stimulated osteoclast differentiation model were established. Cell viability, inflammatory cytokines, osteoclast differentiation, the MAPK signaling pathway, and mitochondrial function before and after treatment with 3o were investigated. In vivo study: Alveolar bone resorption, inflammatory cytokine expression, osteoclast differentiation, and the underlying mechanisms were assessed in mice with periodontitis. Inflammatory cytokine expression and osteoclast differentiation appeared downregulated after 3o treatment. 3o inhibited the MAPK signaling pathway and restored mitochondrial function, including mitochondrial reactive oxygen species, mitochondrial membrane potential, and ATP production. Meanwhile, 3o reduced inflammation activation and bone resorption in mice with periodontitis, reflected by the decreased expression of inflammatory cytokines and osteoclasts, implying that 3o inhibited the MAPK signaling pathway and the mitochondrial oxidative DNA damage marker 8-OHdG. These results highlight the protective role of 3o in periodontitis in mice and reveal an important strategy for preventing periodontitis.
Assuntos
Indóis , Sistema de Sinalização das MAP Quinases , Mitocôndrias , Osteoclastos , Periodontite , Animais , Mitocôndrias/efeitos dos fármacos , Periodontite/tratamento farmacológico , Camundongos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Indóis/farmacologia , Indóis/uso terapêutico , Diferenciação Celular/efeitos dos fármacos , Citocinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Perda do Osso Alveolar/tratamento farmacológico , Camundongos Endogâmicos C57BL , Células RAW 264.7RESUMO
Zinc (Zn)-dysprosium (Dy) binary alloys are promising biodegradable bone fracture fixation implants owing to their attractive biodegradability and mechanical properties. However, their clinical application is a challenge for bone fracture healing, due to the lack of Zn-Dy alloys with tailored proper bio-mechanical and osteointegration properties for bone regeneration. A Zn-5Dy alloy with high strength and ductility and a degradation rate aligned with the bone remodeling cycle is developed. Here, mechanical stability is further confirmed, proving that Zn-5Dy alloy can resist aging in the degradation process, thus meeting the mechanical requirements of fracture fixation. In vitro cellular experiments reveal that the Zn-5Dy alloy enhances osteogenesis and angiogenesis by elevating SIRT4-mediated mitochondrial function. In vivo Micro-CT, SEM-EDS, and immunohistochemistry analyses further indicate good biosafety, suitable biodegradation rate, and great osteointegration of Zn-5Dy alloy during bone healing, which also depends on the upregulation of SIRT4-mediated mitochondrial events. Overall, the study is the first to report a Zn-5Dy alloy that exerts remarkable osteointegration properties and has a strong potential to promote bone healing. Furthermore, the results highlight the importance of mitochondrial modulation and shall guide the future development of mitochondria-targeting materials in enhancing bone fracture healing.
Assuntos
Ligas , Osteogênese , Implantes Absorvíveis , Ligas/química , Ligas/farmacologia , Teste de Materiais , Mitocôndrias/efeitos dos fármacos , Zinco/química , Disprósio/química , Disprósio/farmacologia , Osteogênese/efeitos dos fármacos , Sirtuínas/efeitos dos fármacos , Humanos , Fraturas Ósseas/tratamento farmacológicoRESUMO
Magnesium (Mg) alloys are widely used in bone fixation and bone repair as biodegradable bone-implant materials. However, their clinical application is limited due to their fast corrosion rate and poor mechanical stability. Here, the development of Mg-2Zn-0.5Ca-0.5Sr (MZCS) and Mg-2Zn-0.5Ca-0.5Zr (MZCZ) alloys with improved mechanical properties, corrosion resistance, cytocompatibility, osteogenesis performance, and antibacterial capability is reported. The hot-extruded (HE) MZCZ sample exhibits the highest ultimate tensile strength of 255.8 ± 2.4 MPa and the highest yield strength of 208.4 ± 2.8 MPa and an elongation of 15.7 ± 0.5%. The HE MZCS sample shows the highest corrosion resistance, with the lowest corrosion current density of 0.2 ± 0.1 µA cm-2 and the lowest corrosion rate of 4 ± 2 µm per year obtained from electrochemical testing, and a degradation rate of 368 µm per year and hydrogen evolution rate of 0.83 ± 0.03 mL cm-2 per day obtained from immersion testing. The MZCZ sample shows the highest cell viability in relation to MC3T3-E1 cells among all alloy extracts, indicating good cytocompatibility except at 25% concentration. Furthermore, the MZCZ alloy shows good antibacterial capability against Staphylococcus aureus.
Assuntos
Ligas , Antibacterianos , Magnésio , Teste de Materiais , Osteogênese , Antibacterianos/farmacologia , Antibacterianos/química , Ligas/química , Ligas/farmacologia , Corrosão , Animais , Osteogênese/efeitos dos fármacos , Camundongos , Magnésio/química , Magnésio/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Implantes Absorvíveis , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Zinco/química , Zinco/farmacologia , Linhagem Celular , Estrôncio/química , Estrôncio/farmacologia , Zircônio/química , Zircônio/farmacologiaRESUMO
Zinc (Zn) and some of its alloys are recognized as promising biodegradable implant materials due to their acceptable biocompatibility, facile processability, and moderate degradation rate. Nevertheless, the limited mechanical properties and stability of as-cast Zn alloys hinder their clinical application. In this work, hot-rolled (HR) and hot-extruded (HE) Zn-5 wt.% gadolinium (Zn-5Gd) samples were prepared by casting and respectively combining with hot rolling and hot extrusion for bone-implant applications. Their microstructure evolution, mechanical properties, corrosion behavior, cytotoxicity, antibacterial ability, and in vitro and in vivo osteogenesis were systematically evaluated. The HR and HE Zn-5Gd exhibited significantly improved mechanical properties compared with those of their pure Zn counterparts and the HR Zn-5Gd showed a unique combination of tensile properties with an ultimate tensile strength of â¼311.6 MPa, yield strength of â¼236.5 MPa, and elongation of â¼40.6%, all of which are greater than the mechanical properties required for bone-implant materials. The HR and HE Zn-5Gd showed higher corrosion resistance than their pure Zn counterpart in Hanks' solution and the HE Zn-5Gd had the lowest corrosion rate of 155 µm/y measured by electrochemical corrosion and degradation rate of 26.9 µm/y measured by immersion testing. The HR and HE Zn-5Gd showed high cytocompatibility toward MC3T3-E1 and MG-63 cells, high antibacterial effects against S. aureus, and better in vitro osteogenic activity than their pure Zn counterparts. Furthermore, the HE Zn-5Gd exhibited better in vivo biocompatibility, osteogenesis, and osteointegration ability than pure Zn and pure Ti. STATEMENT OF SIGNIFICANCE: This work reports the mechanical properties, corrosion behaviors, cytocompatibility, antibacterial ability, in vitro and in vivo osteogenesis of biodegradable Zn-Gd alloy for bone-implant applications. Our findings demonstrate that the hot-rolled (HR) Zn-5Gd showed a unique combination of tensile properties with an ultimate tensile strength of â¼311.6 MPa, yield strength of â¼236.5 MPa, and elongation of â¼40.6%. The HR and HE Zn-5Gd showed higher corrosion resistance than their pure Zn counterpart in Hanks' solution. The HR and HE Zn-5Gd showed high cytocompatibility toward MC3T3-E1 and MG-63 cells, good antibacterial effects against S. aureus, and better in vitro osteogenic activity. Furthermore, the HE Zn-5Gd exhibited better in vivo biocompatibility, osteogenesis, and osteointegration ability than pure Zn and pure Ti.
Assuntos
Ligas , Osteogênese , Teste de Materiais , Ligas/farmacologia , Ligas/química , Zinco/farmacologia , Zinco/química , Staphylococcus aureus , Antibacterianos/farmacologia , Implantes Absorvíveis , Corrosão , Materiais Biocompatíveis/químicaRESUMO
Zinc (Zn) and its alloys are used in bone-fixation devices as biodegradable bone-implant materials due to their good biosafety, biological function, biodegradability, and formability. Unfortunately, the clinical application of pure Zn is hindered by its insufficient mechanical properties and slow degradation rate. In this study, a Zn-5 wt.% lanthanum (Zn-5La) alloy with enhanced mechanical properties, suitable degradation rate, and cytocompatibility was developed through La alloying and hot extrusion. The hot-extruded (HE) Zn-5La alloy showed ultimate tensile strength of 286.3 MPa, tensile yield strength of 139.7 MPa, elongation of 35.7%, compressive yield strength of 262.7 MPa, and microhardness of 109.7 HV. The corrosion resistance of the HE Zn-5La in Hanks' and Dulbecco's modified Eagle medium (DMEM) solutions gradually increased with prolonged immersion time. Further, the HE Zn-5La exhibited an electrochemical corrosion rate of 36.7 µm/y in Hanks' solution and 11.4 µm/y in DMEM solution, and a degradation rate of 49.5 µm/y in Hanks' solution and 30.3 µm/y in DMEM solution, after 30 d of immersion. The corrosion resistance of both HE Zn and Zn-5La in DMEM solution was higher than in Hanks' solution. The 25% concentration extract of the HE Zn-5La showed a cell viability of 106.5%, indicating no cytotoxicity toward MG-63 cells. We recommend the HE Zn-5La alloy as a promising candidate material for biodegradable bone-implant applications. STATEMENT OF SIGNIFICANCE: This work reports the mechanical properties, corrosion and degradation behaviors, in vitro cytocompatibility and antibacterial ability of biodegradable Zn-5La alloy for bone-implant applications. Our findings demonstrate that the hot-extruded (HE) Zn-5La alloy showed an ultimate tensile strength of 286.3 MPa, a yield strength of 139.7 MPa, an elongation of 35.7%, compressive yield strength of 262.7 MPa, and microhardness of 109.7 HV. HE Zn-5La exhibited appropriate degradation rates in Hanks' and DMEM solutions. Furthermore, the HE Zn-5La alloy showed good cytocompatibility toward MG-63 and MC3T3-E1 cells and greater antibacterial ability against S. aureus.
Assuntos
Ligas , Zinco , Teste de Materiais , Ligas/farmacologia , Ligas/química , Corrosão , Zinco/farmacologia , Zinco/química , Staphylococcus aureus , Implantes Absorvíveis , Antibacterianos , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/químicaRESUMO
Periodontitis is an oral microbiota-induced inflammatory disease, in which inflammation and oxidative stress play a critical role. Silibinin (SB), a Silybum marianum-derived compound, exhibits strong anti-inflammatory and antioxidative properties. We adopted a rat ligature-induced periodontitis model and a lipopolysaccharide- (LPS-) stimulated human periodontal ligament cells (hPDLCs) model to evaluate the protective effects of SB. In the in vivo model, SB reduced alveolar bone loss and apoptosis of PDLCs in the periodontal tissue. SB also maintained the expression of nuclear factor-E2-related factor 2 (Nrf2), a key regulator of cellular resistance to oxidative stress, and attenuated lipid, protein, and DNA oxidative damages in the periodontal lesion area. Meanwhile, in the in vitro model, SB administration reduced the production of intracellular reactive oxidative species (ROS). Furthermore, SB exerted a strong anti-inflammatory property in both in vivo and in vitro models by inhibiting the expression of inflammatory mediators including nuclear factor-κB (NF-κB) as well as nucleotide binding oligomerization domain- (NOD-) like receptor family pyrin domain-containing 3 (NLRP3) and downregulating the levels of proinflammatory cytokines. This study, for the first time, demonstrates that SB exhibits the anti-inflammatory and antioxidative properties against periodontitis by downregulating the expression of NF-κB and NLRP3 and upregulating Nrf2 expression, suggesting a promising potential clinical application of SB in periodontitis.
Assuntos
NF-kappa B , Periodontite , Ratos , Humanos , Animais , Silibina/farmacologia , Silibina/uso terapêutico , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Regulação para Baixo , Fator 2 Relacionado a NF-E2/metabolismo , Periodontite/tratamento farmacológico , Periodontite/patologia , Inflamação/patologia , Estresse Oxidativo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Lipopolissacarídeos/metabolismoRESUMO
The unique combination of biodegradability, biocompatibility, and functionality of zinc (Zn)-based alloys makes them highly desirable for a wide range of medical applications. However, a long-standing problem associated with this family of biodegradable alloys in the as-cast state is their limited mechanical strength and slow degradation rate. Here we report the development of Zn-xDy (x = 1, 3, and 5 wt.%) alloys with high strength, ductility, cytocompatibility, antibacterial ability, and appropriate degradation rate for biodegradable bone-implant applications. Our results indicate that the mechanical properties of Zn-xDy alloys were effectively improved with increasing Dy addition and hot-rolling due to the second-phase strengthening. The hot-rolled (HR) Zn-3Dy alloy showed the best combined mechanical performance with an ultimate tensile strength of 270.5 MPa, a yield strength of 214.8 MPa, an elongation of 55.1%, and Brinell hardness of 75.9 HB. The corrosion and degradation rates of HR Zn-xDy alloys in Hanks' solution gradually increased with increasing Dy addition due to the intensification of galvanic corrosion. The HR Zn-3Dy alloy showed high antibacterial ability against S. aureus and cytocompatibility toward MC3T3-E1 cells among all the HR alloys. Overall, the HR Zn-3Dy alloy can be considered a promising biodegradable material for bone implants. STATEMENT OF SIGNIFICANCE: This work reports on Zn-xDy (x = 1, 3, and 5%) alloys fabricated by Dy alloying followed by hot-rolling for biodegradable bone-implant applications. Our findings demonstrate that the hot-rolled (HR) Zn-3Dy alloy showed the best combined mechanical performance with an ultimate tensile strength of 270.5 MPa, a yield strength of 214.8 MPa, an elongation of 55.1%, and Brinell hardness of 75.9 HB. The corrosion and degradation rates of HR Zn-xDy alloys in Hanks' solution gradually increased with increasing Dy addition due to the intensification of galvanic corrosion. Furthermore, the HR Zn-3Dy alloy showed greater antibacterial ability against S. aureus and the best cytocompatibility toward MC3T3-E1 cells among all the HR alloys.