It has been revealed that the different morphologies of anodized TiO_2 nanotubes, especially nanotube diameters, triggered different cell behaviors. However, the influence of TiO_2 nanotubes with coexisting multi-size...It has been revealed that the different morphologies of anodized TiO_2 nanotubes, especially nanotube diameters, triggered different cell behaviors. However, the influence of TiO_2 nanotubes with coexisting multi-size diameters on cell behaviors is seldom reported. In this work, coexisting four-diameter TiO_2 nanotube samples, namely,one single substrate with the integration of four different nanotube diameters(60, 150, 250, and 350 nm), were prepared by repeated anodization. The boundaries between two different diameter regions show well-organized structure without obvious difference in height. The adhesion behaviors of MC3T3-E1 cells on the coexisting fourdiameter TiO_2 nanotube arrays were investigated. The results exhibit a significant difference of cell density between smaller diameters(60 and 150 nm) and larger diameters(250 and 350 nm) within 24 h incubation with the coexistence of different diameters, which is totally different from that on the single-diameter TiO_2 nanotube arrays. The coexistence of four different diameters does not change greatly the cell morphologies compared with the singlediameter nanotubes. The findings in this work are expected to offer further understanding of the interaction between cells and materials.展开更多
OBJECTIVE: To identify global research trends in the use of nerve conduits for peripheral nerve injury repair. DATA RETRIEVAL: Numerous basic and clinical studies on nerve conduits for peripheral nerve injury repair w...OBJECTIVE: To identify global research trends in the use of nerve conduits for peripheral nerve injury repair. DATA RETRIEVAL: Numerous basic and clinical studies on nerve conduits for peripheral nerve injury repair were performed between 2002-2011. We performed a bibliometric analysis of the institutions, authors, and hot topics in the field, from the Web of Science, using the key words peripheral nerve and conduit or tube. SELECTION CRITERIA: Inclusion criteria: peer-reviewed published articles on nerve conduits for peripheral nerve injury repair, indexed in the Web of Science; original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. Exclusion criteria: articles requiring manual searching or telephone access; documents not published in the public domain; and several corrected papers. MAIN OUTCOME MEASURES: (a) Annual publication output; (b) publication type; (c) publication by research field; (d) publication by journal; (e) publication by funding agency; (f) publication by author; (g) publication by country and institution; (h) publications by institution in China; (i) most-cited papers. RESULTS: A total of 793 publications on the use of nerve conduits for peripheral nerve injury repair were retrieved from the Web of Science between 2002-2011. The number of publications gradually increased over the 10-year study period. Articles constituted the main type of publication. The most prolific journals were Biomaterials, Microsurgery, and Journal of Biomedical Materials Research Part A. The National Natural Science Foundation of China supported 27 papers, more than any other funding agency. Of the 793 publications, almost half came from American and Chinese authors and institutions. CONCLUSION: Nerve conduits have been studied extensively for peripheral nerve regeneration; however, many problems remain in this field, which are difficult for researchers to reach a consensus.展开更多
Magnesium(Mg)and its alloys have great potential as orthopedic implant candidates,which could release various bioactive substances during degradation.Degradation particles(DPs)are one of the degradation products,but t...Magnesium(Mg)and its alloys have great potential as orthopedic implant candidates,which could release various bioactive substances during degradation.Degradation particles(DPs)are one of the degradation products,but the osteoimmunology effects are still unclear.In this study,the effect of DPs on the polar-ization of macrophages and their release of cytokines was investigated.The results verify that excessive generation of DPs from biodegradable Mg can induce macrophages to realize polarization of proinflamma-tory M1 phenotype.Moreover,macrophages secrete proinflammatory cytokines to inhibit the osteogenic differentiation of rat bone marrow stem cells(rBMSCs).This suggests that the effects of DPs should be considered when evaluating Mg-based implants.DPs continuously produced with the degradation of Mg-based implants may influence osseointegration.展开更多
Magnesium(Mg) has been widely accepted as osteoconductive biomaterial, but osseointegration of Mg device at different implantation sites is still unclear. In the present study, high-purity magnesium(HP Mg)pins were im...Magnesium(Mg) has been widely accepted as osteoconductive biomaterial, but osseointegration of Mg device at different implantation sites is still unclear. In the present study, high-purity magnesium(HP Mg)pins were implanted into femoral shaft and condyle of New Zealand rabbits concurrently. 2, 8, 12 and 16 weeks after surgery, rabbit femurs were harvested for micro-computed tomography(micro-CT) scanning and subsequent histological examinations. HP Mg pins were retrieved for scanning electron microscope and energy dispersive spectrum(SEM/EDS) analyses. HP Mg pins at both implantation sites performed stable corrosion with mineral deposition and bone incorporation on surface. However, difference in distribution of contact osteogenesis centers and biological properties of peri-implant bone tissues was detected between femoral shaft and femoral condyle. In femoral condyle, contact osteogenesis centers originated from both periosteum and cancellous bones and the whole HP Mg pin was encapsuled in trabecular bone at 16 weeks.Meanwhile, bone volume to total bone volume(BV/TV) and bone mineral density(BMD) of peri-implant bone tissues were above those of normal bone tissues. In femoral shaft, contact osteogenesis centers were only from periosteum and direct bone contact was confined in cortical bone, while BV/TV and BMD kept lower than normal. Furthermore, new formation of peri-implant bone tissues was more active in femoral condyle than in femoral shaft at 16 weeks. Therefore, although HP Mg performed good biocompatibility and corrosion behavior in vivo, its bioadaption of osseointegration at different implantations sites should be taken into consideration. Bone metaphysic was suitable for Mg devices where peri-implant bone tissues regenerated rapidly and the biological properties were close to normal bone tissues.展开更多
Bone screws encounter complex mechanical environment in fracture fixation of weight-bearing bone.In the present study, high-purity magnesium(HP Mg) screws were applied in fixation of rabbit femoral intracondylar fract...Bone screws encounter complex mechanical environment in fracture fixation of weight-bearing bone.In the present study, high-purity magnesium(HP Mg) screws were applied in fixation of rabbit femoral intracondylar fracture with 3 mm gap. In the control group, HP Mg screws of the same design were implanted at corresponding position of contralateral leg. At 4, 8 and 16 weeks after surgery, retrieved femurs went through micro-computed tomography(micro-CT) scanning and hard tissue processing. Under mechanical stress involved in fracture fixation, bending of screw bolt was observed at the portion exposed to facture gap at 4 weeks. Then local corrosion at the same portion was detected 16 weeks after surgery,which indicated the accumulation effect of mechanical stress on Mg corrosion. HP Mg screws in the fracture group had no significant difference with the control group in screw volume, surface area, surfaceto-volume ratio(S/V). And peri-implant bone volume/tissues volume(BV/TV) and bone volume density(BMD) in the fracture group was comparable to that in the control group. Furthermore, histological analysis showed new formed bone tissues in fracture gap and fracture healing 16 weeks after surgery. Under mechanical stress, HP Mg screw suffered bolt bending and local corrosion at the portion exposed to fracture gap. But it had no influence on the integral corrosion behaviors, osseointegration of HP Mg screw and the fracture healing. Therefore, HP Mg screws possessed good potential in fracture fixation of weightbearing bones.展开更多
Hydrogen has been used to suppress tumor growth with considerable efficacy.Inhalation of hydrogen gas and oral ingestion of hydrogen-rich saline are two common systemic routes of hydrogen administration.We have develo...Hydrogen has been used to suppress tumor growth with considerable efficacy.Inhalation of hydrogen gas and oral ingestion of hydrogen-rich saline are two common systemic routes of hydrogen administration.We have developed a topical delivery method of hydrogen at targeted sites through the degradation of magnesium-based biomaterials.However,the underlying mechanism of hydrogen’s role in cancer treatment remains ambiguous.Here,we investigate the mechanism of tumor cell apoptosis triggered by the hydrogen released from magnesium-based biomaterials.We find that the localized release of hydrogen increases the expression level of P53 tumor suppressor proteins,as demonstrated by the in vitro RNA sequencing and protein expression analysis.Then,the P53 proteins disrupt the membrane potential of mitochondria,activate autophagy,suppress the reactive oxygen species in cancer cells,and finally result in tumor suppression.The anti-tumor efficacy of magnesium-based biomaterials is further validated in vivo by inserting magnesium wire into the subcutaneous tumor in a mouse.We also discovered that the minimal hydrogen concentration from magnesium wires to trigger substantial tumor apoptosis is 91.2μL/mm^(3)per day,which is much lower than that required for hydrogen inhalation.Taken together,these findings reveal the release of H2 from magnesium-based biomaterial exerts its anti-tumoral activity by activating the P53-mediated lysosome-mitochondria apoptosis signaling pathway,which strengthens the therapeutic potential of this biomaterial as localized anti-tumor treatment.展开更多
Surgical staples made of pure titanium and titanium alloys are widely used in gastrointestinal anastomosis.However the Ti staple cannot be absorbed in human body and produce artifacts on computed tomography(CT)and oth...Surgical staples made of pure titanium and titanium alloys are widely used in gastrointestinal anastomosis.However the Ti staple cannot be absorbed in human body and produce artifacts on computed tomography(CT)and other imaging examination,and cause the risk of incorrect diagnosis.The bioabsorbable staple made from polymers that can degrade in human body environment,is an alternative.In the present study,biodegradable high purity magnesium staples were developed for gastric anastomosis.U-shape staples with two different interior angles,namely original 90and modified 100,were designed.Finite element analysis(FEA)showed that the residual stress concentrated on the arc part when the original staple was closed to B-shape,while it concentrated on the feet for the modified staple after closure.The in vitro tests indicated that the arc part of the original staple ruptured firstly after 7 days immersion,whereas the modified one kept intact,demonstrating residual stress greatly affected the corrosion behavior of the HP-Mg staples.The in vivo implantation showed good biocompatibility of the modified Mg staples,without inflammatory reaction 9 weeks post-operation.The Mg staples kept good closure to the Anastomosis,no leaking and bleeding were found,and the staples exhibited no fracture or severe corrosion cracks during the degradation.展开更多
Magnesium alloys are promising biomaterials for orthopedic implants because of their degradability,osteogenic effects,and biocompatibility.Magnesium has been proven to promote distraction osteogenesis.However,its mech...Magnesium alloys are promising biomaterials for orthopedic implants because of their degradability,osteogenic effects,and biocompatibility.Magnesium has been proven to promote distraction osteogenesis.However,its mechanism of promoting distraction osteogenesis is not thoroughly studied.In this work,a high-purity magnesium pin developed and applied in rat femur distraction osteogenesis.Mechanical test,radiological and histological analysis suggested that high-purity magnesium pin can promote distraction osteogenesis and shorten the consolidation time.Further RNA sequencing investigation found that alternative Wnt signaling was activated.In further bioinformatics analysis,it was found that the Hedgehog pathway is the upstream signaling pathway of the alternative Wnt pathway.We found that Ptch protein is a potential target of magnesium and verified by molecular dynamics that magnesium ions can bind to Ptch protein.In conclusion,HP Mg implants have the potential to enhance bone consolidation in the DO application,and this process might be via regulating Ptch protein activating Hedgehog-alternative Wnt signaling.展开更多
Magnesium(Mg)and its alloys as temporary medical implants with biodegradable and properly mechanical properties have been investigated for a long time.There are already three kinds of biodegradable Mg implants which a...Magnesium(Mg)and its alloys as temporary medical implants with biodegradable and properly mechanical properties have been investigated for a long time.There are already three kinds of biodegradable Mg implants which are approved by Conformite Europeene(CE)or Korea Food and Drug Administration(KFDA),but not China Food and Drug Administration(CFDA,now it is National Medical Products Administration,NMPA).As we know,Chinese researchers,surgeons,and entrepreneurs have tried a lot to research and develop biodegradable Mg implants which might become other new approved implants for clinical applications.So in this review,we present the representative Mg implants of three categories,orthopedic implants,surgical implants,and intervention implants and provide an overview of current achievement in China from academic publications and Chinese patents.We would like to provide a systematic way to translate Mg and its alloy implants from experiment designs to clinical products.展开更多
Magnesium(Mg)screws perform clinical potential in anterior cruciate ligament(ACL)reconstruction,and promote fibrocartilaginous entheses regeneration at the femoral entrance.We aim to prove that high-purity Magnesium(H...Magnesium(Mg)screws perform clinical potential in anterior cruciate ligament(ACL)reconstruction,and promote fibrocartilaginous entheses regeneration at the femoral entrance.We aim to prove that high-purity Magnesium(HP Mg)screws modulate macrophage polarization in fibrocartilage interface regeneration both in vitro and in vivo.HP Mg extracts performed good cytocompatibility and significantly promoted M2 macrophage polarization in the flow cytometry and ELISA assays.M2 macrophages stimulated fibrochondrocyte differentiation of cocultured hBMSCs,and HP Mg extracts had synergistic effect on the process.Then we applied HP Mg screws,with Ti screws as control,in the ACL reconstruction rabbit model.In the histological and immunofluorescence analysis,HP Mg screws inhibited M1 polarization at 2 weeks and highly promoted M2 polarization at 2 and 4 weeks at the tendon–bone interface.Furthermore,regeneration of fibrocartilaginous entheses,rather than the fibrovascular scar interface,was detected in the HP Mg group at 12 weeks.For further mechanism study via RNA-seq detection and WB assays,we found that AKT1 was highly activated in M2 polarization,and HP Mg could stimulate AKT1 expression,rather than AKT2,in the early phase of tendon–bone healing.Our study elucidated macrophage polarization during tendon–bone healing process and emphasized HP Mg on M2 polarization and fibrocartilage interface regeneration via the selective activation of AKT1 and PI3K/AKT pathway.展开更多
Lean alloy(low alloyed)is beneficial for long-term sustainable development of metal materials.Creating a nanocrystalline microstructure is a desirable approach to improve biodegradability and mechanical properties of ...Lean alloy(low alloyed)is beneficial for long-term sustainable development of metal materials.Creating a nanocrystalline microstructure is a desirable approach to improve biodegradability and mechanical properties of lean biomedical Mg alloy,but it is nearly impossible to realize.In the present study,the bulk nanocrystalline Mg alloy(average grain size:~70 nm)was successfully obtained by hot rolling process of a lean Mg-2wt.%Zn(Z2)alloy and both high strength((223 MPa(YS)and 260 MPa(UTS))and good corrosion resistance(corrosion rate in vivo:0.2 mm/year)could be achieved.The microstructure evolution during the rolling process was analyzed and discussed.Several factors including large strain,fine grains,strong basal texture,high temperature and Zn segregation conjointly provided the possibility for the activation of pyramidal<c+a>slip to produce nanocrystals.This finding could provide a new development direction and field of application for lean biomedical Mg alloys.展开更多
Magnesium(Mg)is a promising biomedical metal because of its biodegradability.The crevice between tissue and Mg implant can not be neglected in some implantation sites due to inducing crevice corrosion of Mg.In this pa...Magnesium(Mg)is a promising biomedical metal because of its biodegradability.The crevice between tissue and Mg implant can not be neglected in some implantation sites due to inducing crevice corrosion of Mg.In this paper,a new single mold was designed to build the in vitro experimental setup and four kinds of solutions,i.e.the deionized water(DW),the 0.9 wt.%sodium chloride solution(NaCl),the phosphate buffer saline(PBS)and the modified simulated body fluid(m-SBF)were used to explore necessary factors of crevice corrosion in Mg.It was observed that crevice corrosion in Mg sheets would occur in NaCl and PBS solution under 0.2,0.5 and 0.8 mm crevice thickness.And it was found that there were two necessary factors,i.e.chloride ion and crevice dimension,in crevice corrosion.For the high-purity Mg cannulated screws,crevice corrosion could occur inside tunnel when immersed in PBS.展开更多
To date,few studies have reported on the folding mechanism of tandem G-quadruplexes in human telomeric DNA.Hence,the control of the biofunctions of G-quadruplex,which requires a thorough understanding of its dynamic b...To date,few studies have reported on the folding mechanism of tandem G-quadruplexes in human telomeric DNA.Hence,the control of the biofunctions of G-quadruplex,which requires a thorough understanding of its dynamic behavior,is limited.Here,we investigated the folding/unfolding behavior of human telomeric sequences with lengths over 10 kilonucleotide(knt)by circular dichroism(CD)spectroscopy,UV melting assay,and atomic force microscopy(AFM)-based single-molecule force spectroscopy.展开更多
基金supported by the National Natural Science Foundation of China(No.51401126,No.51271117)Shanghai Committee of Science and Technology,China(No.14441901800)
文摘It has been revealed that the different morphologies of anodized TiO_2 nanotubes, especially nanotube diameters, triggered different cell behaviors. However, the influence of TiO_2 nanotubes with coexisting multi-size diameters on cell behaviors is seldom reported. In this work, coexisting four-diameter TiO_2 nanotube samples, namely,one single substrate with the integration of four different nanotube diameters(60, 150, 250, and 350 nm), were prepared by repeated anodization. The boundaries between two different diameter regions show well-organized structure without obvious difference in height. The adhesion behaviors of MC3T3-E1 cells on the coexisting fourdiameter TiO_2 nanotube arrays were investigated. The results exhibit a significant difference of cell density between smaller diameters(60 and 150 nm) and larger diameters(250 and 350 nm) within 24 h incubation with the coexistence of different diameters, which is totally different from that on the single-diameter TiO_2 nanotube arrays. The coexistence of four different diameters does not change greatly the cell morphologies compared with the singlediameter nanotubes. The findings in this work are expected to offer further understanding of the interaction between cells and materials.
文摘OBJECTIVE: To identify global research trends in the use of nerve conduits for peripheral nerve injury repair. DATA RETRIEVAL: Numerous basic and clinical studies on nerve conduits for peripheral nerve injury repair were performed between 2002-2011. We performed a bibliometric analysis of the institutions, authors, and hot topics in the field, from the Web of Science, using the key words peripheral nerve and conduit or tube. SELECTION CRITERIA: Inclusion criteria: peer-reviewed published articles on nerve conduits for peripheral nerve injury repair, indexed in the Web of Science; original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. Exclusion criteria: articles requiring manual searching or telephone access; documents not published in the public domain; and several corrected papers. MAIN OUTCOME MEASURES: (a) Annual publication output; (b) publication type; (c) publication by research field; (d) publication by journal; (e) publication by funding agency; (f) publication by author; (g) publication by country and institution; (h) publications by institution in China; (i) most-cited papers. RESULTS: A total of 793 publications on the use of nerve conduits for peripheral nerve injury repair were retrieved from the Web of Science between 2002-2011. The number of publications gradually increased over the 10-year study period. Articles constituted the main type of publication. The most prolific journals were Biomaterials, Microsurgery, and Journal of Biomedical Materials Research Part A. The National Natural Science Foundation of China supported 27 papers, more than any other funding agency. Of the 793 publications, almost half came from American and Chinese authors and institutions. CONCLUSION: Nerve conduits have been studied extensively for peripheral nerve regeneration; however, many problems remain in this field, which are difficult for researchers to reach a consensus.
基金This work was financially supported by the Natural Science Foundation of China(No.82160436)the Science and Technol-ogy Commission of Shanghai Municipality(No.19441905600)+2 种基金the“Science and Technology Innovation 2025Major Special Project of Ningbo(No.2019B10064)the Shanghai Jiao Tong Univer-sity Interdisciplinary(Biomedical Engineering)Research Fund(No.ZH2018ZDA09)China Postdoctoral Science Foundation(No.2021M702090).
文摘Magnesium(Mg)and its alloys have great potential as orthopedic implant candidates,which could release various bioactive substances during degradation.Degradation particles(DPs)are one of the degradation products,but the osteoimmunology effects are still unclear.In this study,the effect of DPs on the polar-ization of macrophages and their release of cytokines was investigated.The results verify that excessive generation of DPs from biodegradable Mg can induce macrophages to realize polarization of proinflamma-tory M1 phenotype.Moreover,macrophages secrete proinflammatory cytokines to inhibit the osteogenic differentiation of rat bone marrow stem cells(rBMSCs).This suggests that the effects of DPs should be considered when evaluating Mg-based implants.DPs continuously produced with the degradation of Mg-based implants may influence osseointegration.
基金supported by the National Natural Science Foundation of China(Nos.51271117 and 81371935)the Biomedical Program of Science and Technology Innovation Project supported by Shanghai(Nos.14441901800 and 14441901802)
文摘Magnesium(Mg) has been widely accepted as osteoconductive biomaterial, but osseointegration of Mg device at different implantation sites is still unclear. In the present study, high-purity magnesium(HP Mg)pins were implanted into femoral shaft and condyle of New Zealand rabbits concurrently. 2, 8, 12 and 16 weeks after surgery, rabbit femurs were harvested for micro-computed tomography(micro-CT) scanning and subsequent histological examinations. HP Mg pins were retrieved for scanning electron microscope and energy dispersive spectrum(SEM/EDS) analyses. HP Mg pins at both implantation sites performed stable corrosion with mineral deposition and bone incorporation on surface. However, difference in distribution of contact osteogenesis centers and biological properties of peri-implant bone tissues was detected between femoral shaft and femoral condyle. In femoral condyle, contact osteogenesis centers originated from both periosteum and cancellous bones and the whole HP Mg pin was encapsuled in trabecular bone at 16 weeks.Meanwhile, bone volume to total bone volume(BV/TV) and bone mineral density(BMD) of peri-implant bone tissues were above those of normal bone tissues. In femoral shaft, contact osteogenesis centers were only from periosteum and direct bone contact was confined in cortical bone, while BV/TV and BMD kept lower than normal. Furthermore, new formation of peri-implant bone tissues was more active in femoral condyle than in femoral shaft at 16 weeks. Therefore, although HP Mg performed good biocompatibility and corrosion behavior in vivo, its bioadaption of osseointegration at different implantations sites should be taken into consideration. Bone metaphysic was suitable for Mg devices where peri-implant bone tissues regenerated rapidly and the biological properties were close to normal bone tissues.
基金supported by the National Natural Science Foundation of China (Nos. 51271117 and 81371935)the Biomedical Program of Science and Technology Innovation Project supported by Shanghai (Nos. 14441901800 and 14441901802)
文摘Bone screws encounter complex mechanical environment in fracture fixation of weight-bearing bone.In the present study, high-purity magnesium(HP Mg) screws were applied in fixation of rabbit femoral intracondylar fracture with 3 mm gap. In the control group, HP Mg screws of the same design were implanted at corresponding position of contralateral leg. At 4, 8 and 16 weeks after surgery, retrieved femurs went through micro-computed tomography(micro-CT) scanning and hard tissue processing. Under mechanical stress involved in fracture fixation, bending of screw bolt was observed at the portion exposed to facture gap at 4 weeks. Then local corrosion at the same portion was detected 16 weeks after surgery,which indicated the accumulation effect of mechanical stress on Mg corrosion. HP Mg screws in the fracture group had no significant difference with the control group in screw volume, surface area, surfaceto-volume ratio(S/V). And peri-implant bone volume/tissues volume(BV/TV) and bone volume density(BMD) in the fracture group was comparable to that in the control group. Furthermore, histological analysis showed new formed bone tissues in fracture gap and fracture healing 16 weeks after surgery. Under mechanical stress, HP Mg screw suffered bolt bending and local corrosion at the portion exposed to fracture gap. But it had no influence on the integral corrosion behaviors, osseointegration of HP Mg screw and the fracture healing. Therefore, HP Mg screws possessed good potential in fracture fixation of weightbearing bones.
基金The authors are grateful for support from the National Key Research and Development Program of China(No.2018YFC1106600)the Interdisciplinary Program of Shanghai Jiao Tong University(No.ZH2018QNB07).Thanks to Xinyue Liu(Massachusetts Institute of Technology,MIT)for suggestions for this paper.
文摘Hydrogen has been used to suppress tumor growth with considerable efficacy.Inhalation of hydrogen gas and oral ingestion of hydrogen-rich saline are two common systemic routes of hydrogen administration.We have developed a topical delivery method of hydrogen at targeted sites through the degradation of magnesium-based biomaterials.However,the underlying mechanism of hydrogen’s role in cancer treatment remains ambiguous.Here,we investigate the mechanism of tumor cell apoptosis triggered by the hydrogen released from magnesium-based biomaterials.We find that the localized release of hydrogen increases the expression level of P53 tumor suppressor proteins,as demonstrated by the in vitro RNA sequencing and protein expression analysis.Then,the P53 proteins disrupt the membrane potential of mitochondria,activate autophagy,suppress the reactive oxygen species in cancer cells,and finally result in tumor suppression.The anti-tumor efficacy of magnesium-based biomaterials is further validated in vivo by inserting magnesium wire into the subcutaneous tumor in a mouse.We also discovered that the minimal hydrogen concentration from magnesium wires to trigger substantial tumor apoptosis is 91.2μL/mm^(3)per day,which is much lower than that required for hydrogen inhalation.Taken together,these findings reveal the release of H2 from magnesium-based biomaterial exerts its anti-tumoral activity by activating the P53-mediated lysosome-mitochondria apoptosis signaling pathway,which strengthens the therapeutic potential of this biomaterial as localized anti-tumor treatment.
基金This work was supported by the Natural Science Foundation of China(No.51271117,51571142)the Biomedical program of Science and Technology innovation project supported by Shanghai(No.14441901800).
文摘Surgical staples made of pure titanium and titanium alloys are widely used in gastrointestinal anastomosis.However the Ti staple cannot be absorbed in human body and produce artifacts on computed tomography(CT)and other imaging examination,and cause the risk of incorrect diagnosis.The bioabsorbable staple made from polymers that can degrade in human body environment,is an alternative.In the present study,biodegradable high purity magnesium staples were developed for gastric anastomosis.U-shape staples with two different interior angles,namely original 90and modified 100,were designed.Finite element analysis(FEA)showed that the residual stress concentrated on the arc part when the original staple was closed to B-shape,while it concentrated on the feet for the modified staple after closure.The in vitro tests indicated that the arc part of the original staple ruptured firstly after 7 days immersion,whereas the modified one kept intact,demonstrating residual stress greatly affected the corrosion behavior of the HP-Mg staples.The in vivo implantation showed good biocompatibility of the modified Mg staples,without inflammatory reaction 9 weeks post-operation.The Mg staples kept good closure to the Anastomosis,no leaking and bleeding were found,and the staples exhibited no fracture or severe corrosion cracks during the degradation.
基金This work was sponsored by the National Natural Science Foundation of China(No.81974325,No.81702183)the Science and Technology Commission of Shanghai Municipality(No.18ZR1428700,No.19441903000).
文摘Magnesium alloys are promising biomaterials for orthopedic implants because of their degradability,osteogenic effects,and biocompatibility.Magnesium has been proven to promote distraction osteogenesis.However,its mechanism of promoting distraction osteogenesis is not thoroughly studied.In this work,a high-purity magnesium pin developed and applied in rat femur distraction osteogenesis.Mechanical test,radiological and histological analysis suggested that high-purity magnesium pin can promote distraction osteogenesis and shorten the consolidation time.Further RNA sequencing investigation found that alternative Wnt signaling was activated.In further bioinformatics analysis,it was found that the Hedgehog pathway is the upstream signaling pathway of the alternative Wnt pathway.We found that Ptch protein is a potential target of magnesium and verified by molecular dynamics that magnesium ions can bind to Ptch protein.In conclusion,HP Mg implants have the potential to enhance bone consolidation in the DO application,and this process might be via regulating Ptch protein activating Hedgehog-alternative Wnt signaling.
基金funded by the National Key Research and Development Program of China(No.2018YFC1106600,No.2016YFC1102400)the Natural Science Foundation of China(NSFC No.51571142).
文摘Magnesium(Mg)and its alloys as temporary medical implants with biodegradable and properly mechanical properties have been investigated for a long time.There are already three kinds of biodegradable Mg implants which are approved by Conformite Europeene(CE)or Korea Food and Drug Administration(KFDA),but not China Food and Drug Administration(CFDA,now it is National Medical Products Administration,NMPA).As we know,Chinese researchers,surgeons,and entrepreneurs have tried a lot to research and develop biodegradable Mg implants which might become other new approved implants for clinical applications.So in this review,we present the representative Mg implants of three categories,orthopedic implants,surgical implants,and intervention implants and provide an overview of current achievement in China from academic publications and Chinese patents.We would like to provide a systematic way to translate Mg and its alloy implants from experiment designs to clinical products.
基金sponsored by the National Natural Science Foundation of China(No.81702183,No.81974325)Shanghai Sailing Program(No.17YF1414100).
文摘Magnesium(Mg)screws perform clinical potential in anterior cruciate ligament(ACL)reconstruction,and promote fibrocartilaginous entheses regeneration at the femoral entrance.We aim to prove that high-purity Magnesium(HP Mg)screws modulate macrophage polarization in fibrocartilage interface regeneration both in vitro and in vivo.HP Mg extracts performed good cytocompatibility and significantly promoted M2 macrophage polarization in the flow cytometry and ELISA assays.M2 macrophages stimulated fibrochondrocyte differentiation of cocultured hBMSCs,and HP Mg extracts had synergistic effect on the process.Then we applied HP Mg screws,with Ti screws as control,in the ACL reconstruction rabbit model.In the histological and immunofluorescence analysis,HP Mg screws inhibited M1 polarization at 2 weeks and highly promoted M2 polarization at 2 and 4 weeks at the tendon–bone interface.Furthermore,regeneration of fibrocartilaginous entheses,rather than the fibrovascular scar interface,was detected in the HP Mg group at 12 weeks.For further mechanism study via RNA-seq detection and WB assays,we found that AKT1 was highly activated in M2 polarization,and HP Mg could stimulate AKT1 expression,rather than AKT2,in the early phase of tendon–bone healing.Our study elucidated macrophage polarization during tendon–bone healing process and emphasized HP Mg on M2 polarization and fibrocartilage interface regeneration via the selective activation of AKT1 and PI3K/AKT pathway.
基金This work was funded by the National Key R&D Program of China(No.2018YFC1106600)the“Science and Technology Innovation 2025”Major Special Project of Ningbo(No.2019B10064).
文摘Lean alloy(low alloyed)is beneficial for long-term sustainable development of metal materials.Creating a nanocrystalline microstructure is a desirable approach to improve biodegradability and mechanical properties of lean biomedical Mg alloy,but it is nearly impossible to realize.In the present study,the bulk nanocrystalline Mg alloy(average grain size:~70 nm)was successfully obtained by hot rolling process of a lean Mg-2wt.%Zn(Z2)alloy and both high strength((223 MPa(YS)and 260 MPa(UTS))and good corrosion resistance(corrosion rate in vivo:0.2 mm/year)could be achieved.The microstructure evolution during the rolling process was analyzed and discussed.Several factors including large strain,fine grains,strong basal texture,high temperature and Zn segregation conjointly provided the possibility for the activation of pyramidal<c+a>slip to produce nanocrystals.This finding could provide a new development direction and field of application for lean biomedical Mg alloys.
基金financially supported by the Natural Science Foundation of China(No.51571142)the National Key Research and Development Program of China(No.2018YFC1106600)。
文摘Magnesium(Mg)is a promising biomedical metal because of its biodegradability.The crevice between tissue and Mg implant can not be neglected in some implantation sites due to inducing crevice corrosion of Mg.In this paper,a new single mold was designed to build the in vitro experimental setup and four kinds of solutions,i.e.the deionized water(DW),the 0.9 wt.%sodium chloride solution(NaCl),the phosphate buffer saline(PBS)and the modified simulated body fluid(m-SBF)were used to explore necessary factors of crevice corrosion in Mg.It was observed that crevice corrosion in Mg sheets would occur in NaCl and PBS solution under 0.2,0.5 and 0.8 mm crevice thickness.And it was found that there were two necessary factors,i.e.chloride ion and crevice dimension,in crevice corrosion.For the high-purity Mg cannulated screws,crevice corrosion could occur inside tunnel when immersed in PBS.
基金funded by the National Natural Science Foundation of China(nos.21827805 and 21525418).
文摘To date,few studies have reported on the folding mechanism of tandem G-quadruplexes in human telomeric DNA.Hence,the control of the biofunctions of G-quadruplex,which requires a thorough understanding of its dynamic behavior,is limited.Here,we investigated the folding/unfolding behavior of human telomeric sequences with lengths over 10 kilonucleotide(knt)by circular dichroism(CD)spectroscopy,UV melting assay,and atomic force microscopy(AFM)-based single-molecule force spectroscopy.
