When orthopedic joints coated by hydroxyapatite(HA) were implanted in the human body, they release wear debris into the surrounding tissues. The generation and accumulation of wear particles will induce aseptic loosen...When orthopedic joints coated by hydroxyapatite(HA) were implanted in the human body, they release wear debris into the surrounding tissues. The generation and accumulation of wear particles will induce aseptic loosening. However, the potential bioeffect and mechanism of HA-coated orthopedic implants on bone cells are poorly understood. In this study, defect-related luminescent bur-like hydroxyapatite(BHA) microspheres with the average diameter of 7–9 μm which are comparable to that of the wear-debris particles from aseptically loosened HA implants or HA debris have been synthesized by hydrothermal synthesis and the MC3 T3-E1 cells were set as a cells model to study the potential bioeffect and mechanism of BHA microspheres. The studies demonstrated that BHA microspheres could be taken into MC3 T3-E1 cells via endocytosis involved in micropinocytosisand clathrin-mediated endocytosis process, and exert cytotoxicity effect. BHA microspheres could induce the cell apoptosis by intracellular production of reactive oxygen species(ROS), which led to not only an increase in the permeability of lysosome and release of cathepsins B, but also mitochondrial dysfunction and DNA damage. Our results provide novel evidence to elucidate their toxicity mechanisms and might be helpful for more reasonable applications of HA-based orthopaedic implants in the future.展开更多
Hydroxyapatite(HAP)porous microspheres with very high specific surface area and drug loading capacity,as well as excellent biocompatibility,have been widely used in tumour therapy.Mg^(2+)is considered to be a key fact...Hydroxyapatite(HAP)porous microspheres with very high specific surface area and drug loading capacity,as well as excellent biocompatibility,have been widely used in tumour therapy.Mg^(2+)is considered to be a key factor in bone regeneration,acting as an active agent to stimulate bone and cartilage formation,and is effective in accelerating cell migration and promoting angiogenesis,which is essential for bone tissue repair,anti-cancer,and anti-infection.In this study,abalone shells from a variety of sources were used as raw materials,and Mg^(2+)-doped abalone shell-derived mesoporous HAP microspheres(Mg-HAP)were prepared by hydrothermal synthesis as Mg^(2+)/icariin smart dual delivery system(ICA-Mg-HAP,IMHA).With increasing of Mg^(2+)doping,the surface morphology of HAP microspheres varied from collapsed macroporous to mesoporous to smooth and non-porous,which may be due to Mg^(2+)substitution or coordination in the HAP lattice.At 30%Mg^(2+)doping,the Mg-HAP microspheres showed a more homogeneous mesoporous morphology with a high specific surface area(186.06 m^(2)/g).The IMHA microspheres showed high drug loading(7.69%)and encapsulation rate(83.29%),sustained Mg^(2+)release for more than 27 days,sustained and stable release of icariin for 60 hours,and good responsiveness to pH(pH 6.4>pH 5.6).In addition,the IMHA delivery system stimulated the rapid proliferation of bone marrow mesenchymal stem cells and induced apoptosis in MG63 cells by blocking the G2 phase cycle of osteosarcoma cells and stimulating the high expression of apoptotic genes(Bcl-2,caspase-3,-8,-9).This suggests that the abalone shell-based IMHA may have potential applications in drug delivery and tumour therapy.展开更多
基金supported by the National Natural Science Foundation of China (21301046, 51302062)the Natural Science Foundation of Hebei Province (B2017201125, B2017201100)+1 种基金the Second Batch of Top Youth Talent Support Program of Hebei ProvinceDistinguished Young Scholars Fund of Hebei University (2015JQ04)
文摘When orthopedic joints coated by hydroxyapatite(HA) were implanted in the human body, they release wear debris into the surrounding tissues. The generation and accumulation of wear particles will induce aseptic loosening. However, the potential bioeffect and mechanism of HA-coated orthopedic implants on bone cells are poorly understood. In this study, defect-related luminescent bur-like hydroxyapatite(BHA) microspheres with the average diameter of 7–9 μm which are comparable to that of the wear-debris particles from aseptically loosened HA implants or HA debris have been synthesized by hydrothermal synthesis and the MC3 T3-E1 cells were set as a cells model to study the potential bioeffect and mechanism of BHA microspheres. The studies demonstrated that BHA microspheres could be taken into MC3 T3-E1 cells via endocytosis involved in micropinocytosisand clathrin-mediated endocytosis process, and exert cytotoxicity effect. BHA microspheres could induce the cell apoptosis by intracellular production of reactive oxygen species(ROS), which led to not only an increase in the permeability of lysosome and release of cathepsins B, but also mitochondrial dysfunction and DNA damage. Our results provide novel evidence to elucidate their toxicity mechanisms and might be helpful for more reasonable applications of HA-based orthopaedic implants in the future.
基金supported by Open Foundation of State Key Laboratory of Mineral Processing(No.BGRIMM-KJSKL-2023-23)Shandong Laboratory of Advanced Materials and Green Manufacturing(No.AMGM2021F02)+2 种基金Natural Science Foundation of Shandong Province(Nos.ZR2022QD057,ZR2023MC125)Open Project Fund for Hubei Key Laboratory of Oral and Maxillofacial Development and Regeneration(No.2021kqhm003)China Postdoctoral Science Foundation(Nos.2022M722434,2023T160492).
文摘Hydroxyapatite(HAP)porous microspheres with very high specific surface area and drug loading capacity,as well as excellent biocompatibility,have been widely used in tumour therapy.Mg^(2+)is considered to be a key factor in bone regeneration,acting as an active agent to stimulate bone and cartilage formation,and is effective in accelerating cell migration and promoting angiogenesis,which is essential for bone tissue repair,anti-cancer,and anti-infection.In this study,abalone shells from a variety of sources were used as raw materials,and Mg^(2+)-doped abalone shell-derived mesoporous HAP microspheres(Mg-HAP)were prepared by hydrothermal synthesis as Mg^(2+)/icariin smart dual delivery system(ICA-Mg-HAP,IMHA).With increasing of Mg^(2+)doping,the surface morphology of HAP microspheres varied from collapsed macroporous to mesoporous to smooth and non-porous,which may be due to Mg^(2+)substitution or coordination in the HAP lattice.At 30%Mg^(2+)doping,the Mg-HAP microspheres showed a more homogeneous mesoporous morphology with a high specific surface area(186.06 m^(2)/g).The IMHA microspheres showed high drug loading(7.69%)and encapsulation rate(83.29%),sustained Mg^(2+)release for more than 27 days,sustained and stable release of icariin for 60 hours,and good responsiveness to pH(pH 6.4>pH 5.6).In addition,the IMHA delivery system stimulated the rapid proliferation of bone marrow mesenchymal stem cells and induced apoptosis in MG63 cells by blocking the G2 phase cycle of osteosarcoma cells and stimulating the high expression of apoptotic genes(Bcl-2,caspase-3,-8,-9).This suggests that the abalone shell-based IMHA may have potential applications in drug delivery and tumour therapy.
