Antimicrobial drugs of several classes play an important role in the treatment of bone and joint infections. In addition to fighting pathogenic microorganisms, the effects of drugs on local tissues and cells are also ...Antimicrobial drugs of several classes play an important role in the treatment of bone and joint infections. In addition to fighting pathogenic microorganisms, the effects of drugs on local tissues and cells are also related to the course and prognosis of bone and joint infections. The multi-directional differentiation potential of bone marrow-derived mesenchymal stem cells (MSCs) is essential for tissue repair after local injury, which is directly related to the recovery of bone, cartilage, and medullary adipose tissue. Our previous studies and the literature indicate that certain antimicrobial agents can regulate the differentiation potential of bone marrow-derived MSCs. Here, in order to systematically analyze the effects of various antimicrobial drugs on local tissue regeneration, we comprehensively review the studies on the effects of these drugs on MSC differentiation, and classify them according to the three differentiation directions (osteogenesis, chondrogenesis, and adipogenesis). Our review demonstrates the specific effects of different antimicrobial agents on bone marrow-derived MSCs and the range of concentrations at which they work, and provides a basis for drug selection at different sites of infection.展开更多
A novel zoledronic acid derivative,1-hydroxy-2-(2-propyl-1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid (PIDP), was synthesized by three-step reactions from 2-propyl-1H-imidazole. It was labeled with 99Tcm in condi...A novel zoledronic acid derivative,1-hydroxy-2-(2-propyl-1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid (PIDP), was synthesized by three-step reactions from 2-propyl-1H-imidazole. It was labeled with 99Tcm in conditions of 0.1 mg SnCl2.2H2O at pH 6.0 and 99TcmO4? in aqueous solution for 20 min at room temperature. The labeling yield and radiochemical purity of 99Tcm-PIDP are both higher than 95%. The biodistribution results show that the bone uptake is up to 8.47% ID/g which is the maximum of bone uptake at 30 min after injection of 99Tcm-PIDP in mice. The pharmacokinetic parameters can be estimated from the exponential equation of C=59.565e-11.307t+2.069e-1.211t. The clear bone image of rabbit was obtained at 120 min after injection of 99Tcm-PIDP. The results indicate that 99Tcm-PIDP has highly selective uptake in the skeletal and low uptake, rapid clearance in soft tissues, so it would be a potential novel bone imaging agent.展开更多
TADP, 2-(1H-1,2,4-triazol-1-yl)-1-hydroxyethane-1,1-diphosphonic acid, was synthesized by three step reactions from the raw material 1H-1,2,4-triazole. Tcm-TADP was prepared with 5 mg TADP at pH 7.0 by joining 99 99Tc...TADP, 2-(1H-1,2,4-triazol-1-yl)-1-hydroxyethane-1,1-diphosphonic acid, was synthesized by three step reactions from the raw material 1H-1,2,4-triazole. Tcm-TADP was prepared with 5 mg TADP at pH 7.0 by joining 99 99TcmO4 with SnCl2·2H2O in aqueous solution for 10 min at room temperature. Both labeling yield and radiochemical - purity of Tcm-TADP were more than 95%. The biodistribution in rats and bone scan in rabbits were also studied. The 99 uptake of organ was expressed as %ID/g. The results showed that the bone uptake is up to 17.17%ID/g which is the maximum of bone uptake at 30 min after injection of Tcm-TADP in rats, bone-to-muscle and bone-to-blood uptake 99 ratios were 61.32 and 13.21, respectively. The clear bone image of rabbit was obtained at 120 min after injection of 99Tcm-TADP and clearance in soft tissue was visible. The preparation of 99Tcm-TADP was convenient and 99Tcm-TADP exhibited high uptake in bone, and it would be a potential new bone imaging agent.展开更多
背景:除了铁络合作用外,去铁胺还被认为是一种有效的低氧模拟剂及缺氧诱导因子1α稳定剂,近年的基础及临床研究中去铁胺也表现出良好的骨再生效应。去铁胺溶液或负载去铁胺的生物支架被局部应用于骨组织工程中,其对骨再生的促进涉及多...背景:除了铁络合作用外,去铁胺还被认为是一种有效的低氧模拟剂及缺氧诱导因子1α稳定剂,近年的基础及临床研究中去铁胺也表现出良好的骨再生效应。去铁胺溶液或负载去铁胺的生物支架被局部应用于骨组织工程中,其对骨再生的促进涉及多种功能特性及分子机制,但尚未完全明确,且其在骨再生中的研究进展缺乏有效总结。目的:对去铁胺应用于骨再生的功能特性、优缺点及其在基础研究及临床实践中的进展进行综述,以期为后续相关研究提供参考及策略。方法:以“deferoxamine OR desferrioxamine OR desferal OR DFO”“bone tissue engineering OR bone regeneration OR bone remodeling OR bone repair OR bone healing OR osteogenesis”“angiogenesis OR vascularized bone regeneration OR angiogenic-osteogenic coupling”为英文检索词检索PubMed数据库,以“去铁胺”“骨组织工程,骨再生,骨重建,骨修复,骨愈合”“成血管,血管化成骨,成骨-成血管偶联”为中文检索词检索万方和中国知网数据库,最终纳入88篇文献进行综述。结果与结论:①去铁胺能招募干细胞并调节干细胞功能,激活相关信号通路提高细胞的低氧适应能力,发挥抗炎抗氧化特性改善局部炎性环境,并通过偶联成骨-成血管及抑制骨吸收来促进骨再生。②相较于传统骨组织工程中加载的生长因子或多肽,去铁胺作为小分子药物具有独特的优势,同时也存在毒性反应及应用局限,因此优化载药形式及剂量是必要的。③去铁胺独特的成血管-成骨偶联能力,在不同类型的骨损伤如骨折、骨坏死、牵张成骨、骨移植、口腔相关成骨及骨缺损中,因对骨愈合过程中血管生成的加强而更能适应和解决复杂多变的临床情况及个体差异下造成的骨修复困难;但同时也需要对去铁胺的应用方式及安全剂量加以对比和优化,利于其应用范围的扩大及临床价值的提升。展开更多
目的探讨硫化铜(CuS)/氧化石墨烯(GO)/壳聚糖(CS)/纳米羟基磷灰石(nHA)复合材料(CGCHs)的抗菌和促成骨作用及其作用机制。方法采用水热法合成CuS/GO纳米颗粒,通过原位沉淀法合成CS/nHA支架和CGCHs支架,检测材料表征、光热转换性能和生...目的探讨硫化铜(CuS)/氧化石墨烯(GO)/壳聚糖(CS)/纳米羟基磷灰石(nHA)复合材料(CGCHs)的抗菌和促成骨作用及其作用机制。方法采用水热法合成CuS/GO纳米颗粒,通过原位沉淀法合成CS/nHA支架和CGCHs支架,检测材料表征、光热转换性能和生物安全性,评估CGCHs组和近红外光(NIR)照射下CGCHs(CGCHs+NIR)组的细菌抑制效果及其对细菌生物膜相关基因表达的影响,观察CGCHs和CS/nHA不同材料组的促成骨分化和成骨、破骨相关基因表达。结果CGCHs是具有高度孔隙率的三维支架,在CuS/GO浓度为200μg/mL时CGCHs同时兼具良好的红外升温效果和生物安全性。琼脂糖平板涂菌和细菌死活染色结果均表明CGCHs+NIR组抗菌性能最佳,生物膜相关基因qPCR检测证实其具有抑制细菌生物膜相关基因表达的作用。茜素红染色结果表明CGCHs具有良好的体外促成骨性能,体外共培养3、7、14、21和28 d qPCR结果表明CGCHs对成骨早期和晚期相关基因表达均具有促进作用。与破骨细胞共培养结果可观察到CGCHs具有抑制破骨细胞形成的作用,细胞凋亡检测结果进一步验证这一结论,破骨分化相关基因qPCR检测结果表明,CGCHs主要通过抑制抗酒石酸酸性磷酸酶、组织蛋白酶K、CTR、P65和P38在共培养7、14 d的表达来抑制破骨细胞的分化。结论作为纳米复合材料,CGCHs生物安全性好,具有良好的红外光热协同抗菌作用,在促成骨分化的同时抑制破骨细胞分化,有望为感染性骨缺损治疗提供新的思路。展开更多
Bone fragility has been recognized as a complication of diabetes,both type 1 diabetes (T1D) and type 2 diabetes (T2D),whereas the relationship between prediabetes and fracture risk is less clear.Fractures can deeply i...Bone fragility has been recognized as a complication of diabetes,both type 1 diabetes (T1D) and type 2 diabetes (T2D),whereas the relationship between prediabetes and fracture risk is less clear.Fractures can deeply impact a diabetic patient’s quality of life.However,the mechanisms underlying bone fragility in diabetes are complex and have not been fully elucidated.Patients with T1D generally exhibit low bone mineral density (BMD),although the relatively small reduction in BMD does not entirely explain the increase in fracture risk.On the contrary,patients with T2D or prediabetes have normal or even higher BMD as compared with healthy subjects.These observations suggest that factors other than bone mass may influence fracture risk.Some of these factors have been identified,including disease duration,poor glycemic control,presence of diabetes complications,and certain antidiabetic drugs.Nevertheless,currently available tools for the prediction of risk inadequately capture diabetic patients at increased risk of fracture.Aim of this review is to provide a comprehensive overview of bone health and the mechanisms responsible for increased susceptibility to fracture across the spectrum of glycemic status,spanning from insulin resistance to overt forms of diabetes.The management of bone fragility in diabetic patient is also discussed.展开更多
Bioactive bone cements based on a paste-paste system for orthopaedic applications were developed consisting of hydroxyapatite ( HA ) filler panicles in a methacrylate matrix comprising urethane dimethacrylate ( UD...Bioactive bone cements based on a paste-paste system for orthopaedic applications were developed consisting of hydroxyapatite ( HA ) filler panicles in a methacrylate matrix comprising urethane dimethacrylate ( UDMA ) and triethylene glycol dimethacrylate ( TEGDMA ). To improve the interface between inorganic filler and organic matrix the HA panicles were subjected to two different surface treatment methods, using polyacrylic acid (PAA) and γ-methacryloxy propyl trimethoxy silane (γMPS). The aim of the present study was to determine the influence of surface treatment and the inclusion of multifunctional methacrylates on the mechanical properties, namely 3-point flexural strength (FS) and fracture toughness of the cements and the effect of ageing in simulated body fluid. Comparing the mechanical properties of the two cements, the γMPS- HA cement showed that the fracture toughness of the experimental bone cements were significantly greater ( p 〈 0.001) compared to that of the PMMA cement, whereas PAA-HA containing cement had strength vollues around 20% lower. Interestingly, PAA was found to be more effective in improving the interface as the PAA treated HA cement ( UTHAPPA ) maintained its strength on immersion in SBF, suggesting that PAA provided a coupling, which was less sensitive to moisture, a similar trend was also observed with the inclusion of the carboxyl containing multifunctional methacrylates.展开更多
1概述1.1定义和分类骨质疏松症(osteoporosis)是一种以骨量低下、骨组织微结构损坏,导致骨脆性增加,易发生骨折为特征的全身性骨病[1]。2001年美国国立卫生研究院(National Institutes of Health,NIH)将其定义为骨强度下降和骨折风险增...1概述1.1定义和分类骨质疏松症(osteoporosis)是一种以骨量低下、骨组织微结构损坏,导致骨脆性增加,易发生骨折为特征的全身性骨病[1]。2001年美国国立卫生研究院(National Institutes of Health,NIH)将其定义为骨强度下降和骨折风险增加为特征的骨骼疾病[2]。骨质疏松症可发生于任何年龄,但多见于绝经后女性和老年男性。展开更多
基金National Natural Science Foundation of China,Nos.81472119 and 81672196Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support,No.20161423
文摘Antimicrobial drugs of several classes play an important role in the treatment of bone and joint infections. In addition to fighting pathogenic microorganisms, the effects of drugs on local tissues and cells are also related to the course and prognosis of bone and joint infections. The multi-directional differentiation potential of bone marrow-derived mesenchymal stem cells (MSCs) is essential for tissue repair after local injury, which is directly related to the recovery of bone, cartilage, and medullary adipose tissue. Our previous studies and the literature indicate that certain antimicrobial agents can regulate the differentiation potential of bone marrow-derived MSCs. Here, in order to systematically analyze the effects of various antimicrobial drugs on local tissue regeneration, we comprehensively review the studies on the effects of these drugs on MSC differentiation, and classify them according to the three differentiation directions (osteogenesis, chondrogenesis, and adipogenesis). Our review demonstrates the specific effects of different antimicrobial agents on bone marrow-derived MSCs and the range of concentrations at which they work, and provides a basis for drug selection at different sites of infection.
基金Supported by the National Natural Science Foundation of China (No.20801024)Wu Jieping Medical Found(No.32067500615)
文摘A novel zoledronic acid derivative,1-hydroxy-2-(2-propyl-1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid (PIDP), was synthesized by three-step reactions from 2-propyl-1H-imidazole. It was labeled with 99Tcm in conditions of 0.1 mg SnCl2.2H2O at pH 6.0 and 99TcmO4? in aqueous solution for 20 min at room temperature. The labeling yield and radiochemical purity of 99Tcm-PIDP are both higher than 95%. The biodistribution results show that the bone uptake is up to 8.47% ID/g which is the maximum of bone uptake at 30 min after injection of 99Tcm-PIDP in mice. The pharmacokinetic parameters can be estimated from the exponential equation of C=59.565e-11.307t+2.069e-1.211t. The clear bone image of rabbit was obtained at 120 min after injection of 99Tcm-PIDP. The results indicate that 99Tcm-PIDP has highly selective uptake in the skeletal and low uptake, rapid clearance in soft tissues, so it would be a potential novel bone imaging agent.
文摘TADP, 2-(1H-1,2,4-triazol-1-yl)-1-hydroxyethane-1,1-diphosphonic acid, was synthesized by three step reactions from the raw material 1H-1,2,4-triazole. Tcm-TADP was prepared with 5 mg TADP at pH 7.0 by joining 99 99TcmO4 with SnCl2·2H2O in aqueous solution for 10 min at room temperature. Both labeling yield and radiochemical - purity of Tcm-TADP were more than 95%. The biodistribution in rats and bone scan in rabbits were also studied. The 99 uptake of organ was expressed as %ID/g. The results showed that the bone uptake is up to 17.17%ID/g which is the maximum of bone uptake at 30 min after injection of Tcm-TADP in rats, bone-to-muscle and bone-to-blood uptake 99 ratios were 61.32 and 13.21, respectively. The clear bone image of rabbit was obtained at 120 min after injection of 99Tcm-TADP and clearance in soft tissue was visible. The preparation of 99Tcm-TADP was convenient and 99Tcm-TADP exhibited high uptake in bone, and it would be a potential new bone imaging agent.
文摘背景:除了铁络合作用外,去铁胺还被认为是一种有效的低氧模拟剂及缺氧诱导因子1α稳定剂,近年的基础及临床研究中去铁胺也表现出良好的骨再生效应。去铁胺溶液或负载去铁胺的生物支架被局部应用于骨组织工程中,其对骨再生的促进涉及多种功能特性及分子机制,但尚未完全明确,且其在骨再生中的研究进展缺乏有效总结。目的:对去铁胺应用于骨再生的功能特性、优缺点及其在基础研究及临床实践中的进展进行综述,以期为后续相关研究提供参考及策略。方法:以“deferoxamine OR desferrioxamine OR desferal OR DFO”“bone tissue engineering OR bone regeneration OR bone remodeling OR bone repair OR bone healing OR osteogenesis”“angiogenesis OR vascularized bone regeneration OR angiogenic-osteogenic coupling”为英文检索词检索PubMed数据库,以“去铁胺”“骨组织工程,骨再生,骨重建,骨修复,骨愈合”“成血管,血管化成骨,成骨-成血管偶联”为中文检索词检索万方和中国知网数据库,最终纳入88篇文献进行综述。结果与结论:①去铁胺能招募干细胞并调节干细胞功能,激活相关信号通路提高细胞的低氧适应能力,发挥抗炎抗氧化特性改善局部炎性环境,并通过偶联成骨-成血管及抑制骨吸收来促进骨再生。②相较于传统骨组织工程中加载的生长因子或多肽,去铁胺作为小分子药物具有独特的优势,同时也存在毒性反应及应用局限,因此优化载药形式及剂量是必要的。③去铁胺独特的成血管-成骨偶联能力,在不同类型的骨损伤如骨折、骨坏死、牵张成骨、骨移植、口腔相关成骨及骨缺损中,因对骨愈合过程中血管生成的加强而更能适应和解决复杂多变的临床情况及个体差异下造成的骨修复困难;但同时也需要对去铁胺的应用方式及安全剂量加以对比和优化,利于其应用范围的扩大及临床价值的提升。
文摘目的探讨硫化铜(CuS)/氧化石墨烯(GO)/壳聚糖(CS)/纳米羟基磷灰石(nHA)复合材料(CGCHs)的抗菌和促成骨作用及其作用机制。方法采用水热法合成CuS/GO纳米颗粒,通过原位沉淀法合成CS/nHA支架和CGCHs支架,检测材料表征、光热转换性能和生物安全性,评估CGCHs组和近红外光(NIR)照射下CGCHs(CGCHs+NIR)组的细菌抑制效果及其对细菌生物膜相关基因表达的影响,观察CGCHs和CS/nHA不同材料组的促成骨分化和成骨、破骨相关基因表达。结果CGCHs是具有高度孔隙率的三维支架,在CuS/GO浓度为200μg/mL时CGCHs同时兼具良好的红外升温效果和生物安全性。琼脂糖平板涂菌和细菌死活染色结果均表明CGCHs+NIR组抗菌性能最佳,生物膜相关基因qPCR检测证实其具有抑制细菌生物膜相关基因表达的作用。茜素红染色结果表明CGCHs具有良好的体外促成骨性能,体外共培养3、7、14、21和28 d qPCR结果表明CGCHs对成骨早期和晚期相关基因表达均具有促进作用。与破骨细胞共培养结果可观察到CGCHs具有抑制破骨细胞形成的作用,细胞凋亡检测结果进一步验证这一结论,破骨分化相关基因qPCR检测结果表明,CGCHs主要通过抑制抗酒石酸酸性磷酸酶、组织蛋白酶K、CTR、P65和P38在共培养7、14 d的表达来抑制破骨细胞的分化。结论作为纳米复合材料,CGCHs生物安全性好,具有良好的红外光热协同抗菌作用,在促成骨分化的同时抑制破骨细胞分化,有望为感染性骨缺损治疗提供新的思路。
文摘Bone fragility has been recognized as a complication of diabetes,both type 1 diabetes (T1D) and type 2 diabetes (T2D),whereas the relationship between prediabetes and fracture risk is less clear.Fractures can deeply impact a diabetic patient’s quality of life.However,the mechanisms underlying bone fragility in diabetes are complex and have not been fully elucidated.Patients with T1D generally exhibit low bone mineral density (BMD),although the relatively small reduction in BMD does not entirely explain the increase in fracture risk.On the contrary,patients with T2D or prediabetes have normal or even higher BMD as compared with healthy subjects.These observations suggest that factors other than bone mass may influence fracture risk.Some of these factors have been identified,including disease duration,poor glycemic control,presence of diabetes complications,and certain antidiabetic drugs.Nevertheless,currently available tools for the prediction of risk inadequately capture diabetic patients at increased risk of fracture.Aim of this review is to provide a comprehensive overview of bone health and the mechanisms responsible for increased susceptibility to fracture across the spectrum of glycemic status,spanning from insulin resistance to overt forms of diabetes.The management of bone fragility in diabetic patient is also discussed.
文摘Bioactive bone cements based on a paste-paste system for orthopaedic applications were developed consisting of hydroxyapatite ( HA ) filler panicles in a methacrylate matrix comprising urethane dimethacrylate ( UDMA ) and triethylene glycol dimethacrylate ( TEGDMA ). To improve the interface between inorganic filler and organic matrix the HA panicles were subjected to two different surface treatment methods, using polyacrylic acid (PAA) and γ-methacryloxy propyl trimethoxy silane (γMPS). The aim of the present study was to determine the influence of surface treatment and the inclusion of multifunctional methacrylates on the mechanical properties, namely 3-point flexural strength (FS) and fracture toughness of the cements and the effect of ageing in simulated body fluid. Comparing the mechanical properties of the two cements, the γMPS- HA cement showed that the fracture toughness of the experimental bone cements were significantly greater ( p 〈 0.001) compared to that of the PMMA cement, whereas PAA-HA containing cement had strength vollues around 20% lower. Interestingly, PAA was found to be more effective in improving the interface as the PAA treated HA cement ( UTHAPPA ) maintained its strength on immersion in SBF, suggesting that PAA provided a coupling, which was less sensitive to moisture, a similar trend was also observed with the inclusion of the carboxyl containing multifunctional methacrylates.
文摘1概述1.1定义和分类骨质疏松症(osteoporosis)是一种以骨量低下、骨组织微结构损坏,导致骨脆性增加,易发生骨折为特征的全身性骨病[1]。2001年美国国立卫生研究院(National Institutes of Health,NIH)将其定义为骨强度下降和骨折风险增加为特征的骨骼疾病[2]。骨质疏松症可发生于任何年龄,但多见于绝经后女性和老年男性。