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    08 December 2023, Volume 27 Issue 34 Previous Issue    Next Issue
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    Comparison of random forest model and logistic regression model in predicting the prolonged length of stay of hip fracture patients
    Yu Jian, Zhou Bingqian, Wang Zhao, Li Yue, Chang Yaru, Cao Hong
    2023, 27 (34):  5413-5420.  doi: 10.12307/2023.744
    Abstract ( 1366 )   PDF (1277KB) ( 49 )   Save
    BACKGROUND: The incidence of hip fracture patients is increasing day by day. Because of their poor physical condition, these people often need to stay in hospital for a long time. However, the prolonged length of stay leads to a decrease in bed circulation rate and an increase in economic burden. At present, there are few prediction models for delayed discharge of hip fractures. This study aims to find the best model for delayed discharge of hip fractures and guide clinical decision-making.  
    OBJECTIVE: To explore the risk factors of prolonged length of stay in patients with hip fractures, establish two different risk prediction models, obtain the best risk prediction tools, and provide a reference for clinical intervention and management.
    METHODS: Data from 683 elderly patients with hip fractures in Tianjin Hospital from January 2019 to December 2021 were retrospectively analyzed. All patients were randomly divided into a modeling group (479 cases) and a verification group (204 cases) according to the ratio of 7:3. The 75th percentile of length of stay was taken as the cut-off point (> 28 days), and they were divided into extended hospitalization group and normal group. Single-factor and multifactor Logistic regression analysis and variable importance ranking were used to screen the best prediction model; the nomogram and random forest models were constructed. The prediction efficiency of the two models was evaluated by the receiver operating characteristic curve area, accuracy, sensitivity, specificity, positive prediction value and negative prediction value.  
    RESULTS AND CONCLUSION: (1) Logistic regression analysis showed that bone traction, pneumonia, refolding, multiple trauma, venous thrombosis, lung infection and age-adjusted Charlson Comorbidity Index were the risk factors of prolonged length of stay of hip fracture patients. (2) The random forest model showed that age, bone traction, surgical type, age-adjusted Charlson Comorbidity Index and pneumonia were the first five indexes according to the average reduction of the Gini index, which had an important influence on the prediction of delayed discharge. (3) The area under the receiver operating characteristic curve, accuracy, sensitivity, specificity, positive prediction value and negative prediction value of the Logistic regression model and random forest prediction model were 0.774(95%CI: 0.696-0.853) and 0.708(95%CI: 0.627-0.789), 60.78% and 90.85%, 80.39% and 23.53%, 50.82% and 78.09%, 86.01% and 46.15%, respectively. The results exhibited that the Logistic model had good prediction efficiency. (4) Above findings confirm that the Logistics regression model and random forest model have high predictive value for a prolonged length of stay in patients with hip fractures, which is of great significance for clinical medical staff to identify high-risk patients in time and take effective intervention measures to reduce the length of stay of patients with hip fractures.
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    Repair of rabbit cartilage defects with double-layer bionic scaffold loaded with nerve growth factor cartilage and subchondral bone
    Zhou Jie, Ye Peng, Zhang Tianxi, Li Xingyu, Li Shasha, Yu Anyong, Deng Jiang
    2023, 27 (34):  5421-5429.  doi: 10.12307/2023.804
    Abstract ( 284 )   PDF (2525KB) ( 136 )   Save
    BACKGROUND: The outcome of large osteochondral defects is poor. Double-layer or multi-layer scaffolds have become a new treatment strategy because they are more consistent with cartilage anatomy and mimicry. 
    OBJECTIVE: To investigate the repair effect of nerve growth factor/type II collagen-silk fibroin-chitosan/type I collagen-silk fibroin-chitosan-nano hydroxyapatite cartilage and subchondral bone bionic scaffold in the repair of cartilage defects.  
    METHODS: Double-layer scaffolds loaded with type II collagen-silk fibroin-chitosan/type I collagen-silk fibroin-chitosan-nano hydroxyapatite were prepared by freeze-drying, emulsification, and solvent evaporation. The physical and chemical properties of the scaffolds were tested and the appropriate proportion of scaffold components was selected for animal experiments. A double-layer scaffold containing nerve growth factor was prepared by immersion in nerve growth factor sustained-release microsphere solution. Thirty New Zealand white rabbits were randomly divided into three groups (n=10). An osteochondral defect model was established. The blank control group did not receive any treatment. The control group was implanted with a double-layer scaffold without nerve growth factor. The experimental group was implanted with a double-layer scaffold loaded with nerve growth factor. The gross observation of cartilage repair and the morphological observation of cartilage tissue were performed 4, 8 and 12 weeks after operation.
    RESULTS AND CONCLUSION: (1) The relevant results of porosity, water absorption expansion rate, and hot water dissolution rate concluded that when the mass ratio of type II collagen:silk fibroin:chitosan in the upper scaffold was 1:1:1, and the mass ratio of type I collagen:silk fibroin:chitosan:nano-hydroxyapatite in the lower scaffold was 1:1:1:1. The double-layer scaffold had good physical and chemical properties and was suitable for animal experiments. (2) The average particle size of the sustained release of nerve growth factor microspheres was (25.87±6.54) μm, the drug loading capacity was 0.516 μg/mg, and the encapsulation rate was 40.5%. (3) In animal experiments, the gross observation results showed that the cartilage repair of the experimental group was faster than that of the control group and the blank control group, and the repair effect was the best. Hematoxylin-eosin staining and alxin blue staining showed that fibrous tissue and a small number of cartilage lacunae were visible in the defect area of the blank control group at 12 weeks after surgery; most of the repaired tissue in the damaged area of the control group was fibrocartilage, and the subchondral bone was not completely rebuilt, and the boundary between the osteochondral layer was not clear. In the experimental group, the repair between the cartilage layer and the subchondral bone layer was complete, the boundary was obvious, and the tide line was visible. Immunohistochemical staining showed that type II collagen in the repaired cartilage of the experimental group was more than that in the control group and the blank control group at 12 weeks after surgery. (4) The double-layer bionic scaffold of cartilage and subchondral bone with good physical and chemical properties was successfully prepared in the experiment. The scaffold loaded with nerve growth factor could better promote the repair of rabbit cartilage defects.
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    Graphene oxide-chitosan composite coating affects the biological behavior of osteoblasts
    Huang Qian, Hao Liying, He Longlong, Du Liangzhi
    2023, 27 (34):  5430-5435.  doi: 10.12307/2023.542
    Abstract ( 273 )   PDF (1322KB) ( 50 )   Save
    BACKGROUND: As a coating material, chitosan can effectively improve biological properties of medical metal surfaces due to its excellent film-forming and metal binding abilities. However, the biological activity and osteoinductive ability of chitosan are insufficient. Graphene oxide can improve the mechanical properties and biocompatibility of various polymer materials, as well as promote osteogenic differentiation. The combination of chitosan and graphene oxide may have better biological properties and osteogenic activity.
    OBJECTIVE: To construct the graphene oxide-modified chitosan composite coating material, analyze the surface morphology, chemical composition, and physical properties of the coating material, as well as the effects of the coating materials on proliferation, adhesion, and osteogenic differentiation of osteoblasts.
    METHODS: The titanium surface was treated with 3-aminopropyltriethoxysilane to form silane groups on the surface, and then glutaraldehyde was used to cross-link chitosan with silane groups to prepare simple chitosan coating and graphene oxide/chitosan composite coating, respectively. The surface morphology, chemical structure and hydrophilic properties of the coatings were characterized by atomic force microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, and contact angle measurement system. Rat osteoblasts were seeded on the surface of the two materials, and the proliferation, spreading, and osteogenic differentiation of rat osteoblasts were analyzed by CCK-8 assay, scanning electron microscopy, and reverse transcription-polymerase chain reaction analysis.
    RESULTS AND CONCLUSION: (1) The thickness of the graphene oxide sheets was about 2 nm as measured by atomic force microscopy; the scanning electron microscopy showed that the surfaces of both coatings were smooth and dense, in which the chitosan molecules were closely arranged and the graphene oxide was uniformly distributed in the chitosan, while wrinkles appeared on the surface of chitosan due to the addition of grapheme. The contact angle of the graphene oxide-chitosan composite coating was significantly smaller than the chitosan coating alone (P < 0.05). (2) CCK-8 assay showed that the graphene oxide-chitosan composite coating better promoted the proliferation of osteoblasts compared with the chitosan coating alone. (3) The scanning electron microscopy showed that better spreading was found in osteoblasts on the surface of the graphene oxide-chitosan composite coating compared with the chitosan coating alone. (4) Reverse transcription-polymerase chain reaction analysis showed that the mRNA expression of alkaline phosphatase and Runx2 was significantly increased in the graphene oxide/chitosan composite coating group compared with in the chitosan coating alone group (P < 0.05). (5) These findings suggest that graphene oxide/chitosan composite coating had good biocompatibility, physicochemical, and osteoinductive properties.
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    Effect of vertebral augmentation using quantitative computed tomography-based finite element analysis on biomechanical parameters of non-enhanced vertebrae in different locations
    Liu Jin, Xia Bin, Cai Peng, Gu Zuchao, Yang Haosen, Tang Jing
    2023, 27 (34):  5436-5440.  doi: 10.12307/2023.778
    Abstract ( 277 )   PDF (1339KB) ( 36 )   Save
    BACKGROUND: Whether the huge difference in biomechanical properties between bone cement and osteoporotic vertebral body will increase the occurrence of refracture is still controversial. The extent to which cement implantation will affect the biomechanical parameters of unaugmented vertebrae remains unclear.  
    OBJECTIVE: To analyze the influence range of vertebral augmentation on biomechanical parameters of the osteoporotic spine through the finite element model of long-segment osteoporotic vertebral compression fracture based on quantitative CT.
    METHODS: The osteoporotic compression fracture model of T12 vertebrae with a long segment of T4-L5 was constructed based on quantitative CT data. On the basis of 150 N vertical load, 1.5 N•m torsional torque was applied to the model in different directions to simulate flexion, extension, lateral flexion and rotation. The stress changes of the vertebral bodies, intervertebral disc and facet joint were compared before and after bone cement implantation.  
    RESULTS AND CONCLUSION: (1) After implantation of model bone cement, the overall displacement amplitude of each movement state decreased by 16% on average. (2) The stress of the fifth vertebrae away from the treated vertebra at the cephalic side increased by approximately 20% on average; the stress of the first intervertebral disc at the cephalic side decreased by approximately 20%, and the stress of the second and third intervertebral discs increased by approximately 4% and 2%, respectively. The stress of the facet joints of the treated vertebrae and its caudal adjacent vertebrae decreased by approximately 6%, and the stress of the other caudal facet joints and the four cephalic adjacent facet joints increased to different degrees. In addition, the stress changes tended to be more significant the closer to the treated vertebra. (3) The results of this study show that the stress of multiple vertebral body, intervertebral discs and facets at the cephalic and caudal sides from the augmented vertebra will be significantly changed by cement implantation, and the closer to the treated vertebra, the more obvious the effect is. This stress change may be associated with the occurrence of new fractures after vertebral augmentation.
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    Biological properties of nano-hydroxyapatite-zinc oxide composite scaffolds and their effects on the behavior of MC3T3-E1 osteoblasts
    Liu Zixuan, Li Yan, Ji Lin, Xia Delin
    2023, 27 (34):  5441-5447.  doi: 10.12307/2023.803
    Abstract ( 266 )   PDF (1492KB) ( 51 )   Save
    BACKGROUND: It has been found that the mechanical properties of nano-hydroxyapatite can be improved by doping zinc ions in nano-hydroxyapatite. 
    OBJECTIVE: To investigate the biological properties of nano-hydroxyapatite ceramic scaffold mixed with different concentrations of zinc oxide, and to study the effects of the scaffold on the biological behavior of MC3T3-E1 osteoblasts.
    METHODS: Nano-hydroxyapatite ceramic scaffolds containing different mass fractions (0%, 0.5%, 1.5%, 2.5%, 3.5%) of zinc oxide were prepared by a chitin gel system to characterize the physical properties of scaffolds. The five groups of nano-hydroxyapatite-zinc oxide composite scaffolds were co-cultured with MC3T3-E1 osteoblasts. Calcein AM/PI staining, CCK-8 assay, CellTiter LumiTM Luminescent assay, alkaline phosphatase activity detection, alizarin red staining, and quantitative analysis of calcium ions were detected. 
    RESULTS AND CONCLUSION: (1) Under a scanning electron microscope, the surface of the nano-hydroxyapatite-zinc oxide composite scaffolds had three-dimensional perforated pores. The pore size of the composite scaffolds was uniform, ranging from 300 to 400 μm, and the porosity was above 70%. With the increase of the mass fraction of zinc oxide, the compressive strength of the composite scaffold increased gradually. (2) Calcein-AM/PI staining showed no obvious cytotoxicity in the five groups, and the survival rate of cells in the 2.5% group was higher than that in the 0% group (P < 0.05). CCK-8 assay and CellTiter-LumiTM luminescent assay showed that cell proliferation and activity of each group were in the order from strong to weak: 2.5% group >1.5% group > 0.5% group > 0% group > 3.5% group. The order of alkaline phosphatase activity from high to low was 2.5% group > 1.5% group > 3.5% group > 0.5% group > 0% group. Alizarin red staining and quantitative analysis of calcium ions showed that the formation ability of cell mineralized nodules was in the order of 2.5% group > 1.5% group > 0.5% group > 3.5% group > 0% group from strong to weak. (3) The results showed that zinc oxide doping improved the mechanical properties of nano-hydroxyapatite scaffolds and promoted the proliferation and differentiation of osteoblasts, among which the composite scaffolds doped with 2.5% zinc oxide had the best proliferation and differentiation ability of osteoblasts.
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    Preparation of cartilage decellularized extracellular matrix-loaded composite nanofiber scaffolds based on two-nozzle electrospinning
    Teng Jianxiang, Zhu Jisheng, Yuan Daizhu, Wang Zhen, Zhou Yuhu, Tian Xiaobin
    2023, 27 (34):  5448-5454.  doi: 10.12307/2023.839
    Abstract ( 286 )   PDF (1891KB) ( 47 )   Save
    BACKGROUND: Cartilage decellularized extracellular matrix (dECM) is an ideal biomaterial for the preparation of cartilage tissue engineering scaffolds, which can be used to repair cartilage defects.
    OBJECTIVE: To use polyvinyl alcohol (PVA) as the loading material of dECM and poly3-hydroxybutyrate 4-hydroxybutyrate (P34HB) as the frame material to prepare P34HB-PVA-dECM composite nanofiber scaffolds by two-needle electrospinning, and preliminarily explore the bioactivity of the scaffolds in vitro.
    METHODS: The cellular components in the cartilage tissue were removed by a combination of enzyme, chemical, and ultrasonic concussion cleaning methods to prepare cartilage dECM. P34HB, P34HB-PVA, and P34HB-PVA-dECM scaffolds were prepared by two-neezle electrospinning. The fiber morphology, composition, hydrophilicity, and mechanical properties of the scaffolds were characterized. Human bone marrow mesenchymal stem cells were co-cultured with the three kinds of scaffolds. The viability of cells on scaffolds was evaluated by the Live/Dead staining. The adhesion morphology of the cells on the scaffolds was observed by scanning electron microscopy. The proliferation performance of the cells on the scaffolds was detected by the alamar blue kit. The chondrogenic differentiation of human bone marrow stem cells on the scaffolds was evaluated by type II collagen immunofluorescence.

    RESULTS AND CONCLUSION: (1) Scanning electron microscopy results showed that the scaffold fibers in each group were randomly distributed and the interconnections between the fibers showed a porous structure. The fiber diameter of P34HB-PVA-dECM scaffolds was the smallest. The P34HB-PVA-dECM scaffolds had the smallest water contact angle (P < 0.05) and the highest water absorption rate compared with the P34HB and P34HB-PVA scaffolds (P < 0.05). The elastic modulus of the P34HB-PVA-dECM scaffolds was higher than that of the P34HB and P34HB-PVA scaffolds (P < 0.05). (2) Live/Dead staining showed that most cells survived well on the three groups of scaffolds. The scanning electron microscope observation showed that the bone marrow mesenchymal stem cells on P34HB-PVA-dECM scaffolds extended pseudopod more fully and fused better with the scaffolds. Alamar blue staining exhibited that the proliferation rate of bone marrow mesenchymal stem cells on the P34HB-PVA-dECM scaffolds was faster than that on the P34HB and P34HB-PVA scaffolds (P < 0.05). The immunofluorescence staining results showed that more type II collagen produced after chondrogenic induction on the P34HB-PVA-dECM scaffolds was more than that on the P34HB and P34HB-PVA scaffolds (P < 0.05). (3) To sum up, the P34HB-PVA-dECM composite nanofiber scaffolds have smaller fiber structure, more optimized hydrophilicity and mechanical properties, which is more favorable for the adhesion, proliferation, and differentiation into chondrocytes of bone marrow mesenchymal stem cells. 

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    Regulation of interleukin-4 on osteoclast differentiation during bone regeneration guided by bone replacement materials
    Li Li, Li Xiao, Li Duchenhui, Zhang Jie, Xiao Tianjiao, Kang Jiabing, Tian Ai
    2023, 27 (34):  5455-5461.  doi: 10.12307/2023.840
    Abstract ( 245 )   PDF (2800KB) ( 82 )   Save
    BACKGROUND: Studies have shown that a certain dose of interleukin-4 intervention can yield the appropriate ratio of M1/M2 macrophage profile to generate a microenvironment conducive to bone healing and promoting bone regeneration. 
    OBJECTIVE: To investigate the effect of interleukin-4 on NLRP3 inflammasome activation and osteoclast differentiation during bone tissue regeneration guided by bone replacement materials.
    METHODS: Forty-eight 6-8-week-old male SD rats were selected to establish a 5-mm diameter cranial bone defect model on the left and implanted with Bio-Oss bone replacement material at the same time, and the periosteum was sutured. Rat models were randomly divided into control and experimental groups (n=24) at postoperative 3 days. Interleukin-4 and PBS were injected locally into the cranial bone defect area for the experimental and control groups, once a day, for 5 consecutive days. SD rats were executed at 1 and 2 weeks after surgery and skull samples were taken. Immunohistochemical staining was performed to detect the expression of cleaved caspase-1 and interleukin-1β protein. Immunofluorescence staining was performed to observe the expression of inducible nitric oxide synthase (M1 surface marker) and cleaved caspase-1 (NLRP3 indicator). Real-time fluorescence quantitative PCR was performed to detect the expression of related inflammatory factors caspase-1, interleukin-1β and osteoclast factor histone K gene. The differentiation and number of osteoclasts were observed by anti-tartrate acid phosphatase staining. At 6 and 12 weeks after surgery, micro-CT and hematoxylin-eosin staining were performed to observe the osteogenesis of the skull. 
    RESULTS AND CONCLUSION: (1) Immunofluorescence staining showed that the number of inducible nitric oxide synthase and cleaved caspase-1 double-stained cells in the experimental group was significantly lower than that in the control group at 1 and 2 weeks (P < 0.05). (2) Immunohistochemical staining showed that the expression of cleaved caspase-1 and interleukin-1β in the experimental group was significantly lower than that in the control group at 1 week (P < 0.05). (3) RT-qPCR suggested that the expression of caspase-1 mRNA in the experimental group was lower than that in the control group at 1 week (P < 0.05). The expression intensity of interleukin-1β and osteoclast factor histone K mRNA was significantly lower in the experimental group than that in the control group at postoperative 1 and 2 weeks (P < 0.05). (4) Anti-tartrate acid phosphatase staining showed that the number of osteoclasts was significantly lower in the experimental group at 1 and 2 weeks than that in the control group (P < 0.05). (5) Micro-CT results showed that the bone volume fraction and bone mineral density in the bone defect area were significantly higher in the experimental group than those in the control group at 6 and 12 weeks after injection (P < 0.05). Hematoxylin-eosin staining showed that 12 weeks after injection, multiple ossification centers were formed in the center of the defect in the experimental group, with scattered mature bone cells and lacunae, and a large number of osteoblasts around the material arranged into a single layer to participate in the formation of bone matrix. (6) The results suggest that interleukin-4 may be involved in downregulating NLRP3 inflammasome expression, inhibiting the activation of caspase-1 and thus reducing the secretion of interleukin-1β, reducing the inflammatory state of the local microenvironment, as well as inhibiting osteoclast differentiation and playing a role in promoting new bone production during bone tissue regeneration guided by bone replacement materials. 
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    Establishment of transient expression system of eggplant cotyledon by agrobacterium-mediated injection
    Lang Yaoling, Wang Qian, Chen Bin, Bai Guohui, Guan Xiaoyan, Liu Jianguo
    2023, 27 (34):  5462-5468.  doi: 10.12307/2023.747
    Abstract ( 309 )   PDF (1302KB) ( 69 )   Save
    BACKGROUND: The production of oral vaccines by transgenic plants has great advantages and broad application prospects. At present, there are few reports on the study of the tomato transient expression system. It is necessary to optimize tomato transient expression conditions, which can greatly improve the genetic transformation efficiency of plants. 
    OBJECTIVE: The transient expression system of eggplant cotyledon was established by Agrobacterium tumefaciens-mediated injection to detect the transcription level of exogenous genes in plant expression vector pCAMBIA-E8-APB-DOCK8.
    METHODS: Through the cultivation of tomato bacterial-free seedlings, significant differences in the number of sprouts, seedlings and agronomic traits of different tomato varieties were observed, and the tomato varieties suitable for this experiment were selected. The plant expression vector pCAMBIA-E8-APB-DOCK8 constructed earlier was transformed into Agrobacterium tumefaciens EHA105, and then the tomato cotyledons, the concentration of Agrobacterium tumefaciens injected, the amount of Agrobacterium tumefaciens injected, the age of seedlings and the days of coculture were screened. The transient expression system of eggplant cotyledon mediated by Agrobacterium tumefaciens was established to observe the transcriptional level of the reporter gene.RESULTS AND CONCLUSION: The transient expression system of eggplant cotyledon was preliminarily established. The suitable tomato variety was selected as European Dahong (apple type), and the selected material was tomato cotyledon. The concentration of Agrobacterium for injection was A600:0.2-0.7, and the amount of Agrobacterium for injection was 50 μL. The seedling age was 7-10 days, and the total culture time was 24-48 hours. It provides a convenient, fast and effective method for the analysis of exogenous gene protein expression in the later stage.
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    Construction and in vivo osteogenesis of microspheres loaded with immunomodulatory peptide/miR-26a complexes for slow release
    Li Xinlun, Zhu Yushu, Yang Yiling, He Siqi, Wen Nan, Mu Yandong
    2023, 27 (34):  5469-5476.  doi: 10.12307/2023.557
    Abstract ( 392 )   PDF (3092KB) ( 106 )   Save
    BACKGROUND: Our group has demonstrated that the immunomodulatory peptide DP7-C has good immunomodulatory functions and can efficiently transfect and deliver miRNAs into cells to exert regulatory functions. 
    OBJECTIVE: To prepare and screen porous poly(lactic-co-glycolic acid) microspheres of different sizes loaded with immunomodulatory peptide miR-26a complexes, construct and optimize the sustained release system, and verify its biocompatibility and osteogenic ability in vivo.
    METHODS: (1) Microsphere preparation: Porous poly(lactic-co-glycolic acid) microspheres were prepared by double emulsification with NH4HCO3 as the pore-forming agent. Three different sizes of porous poly(lactic-co-glycolic acid) microspheres were prepared by adjusting the rotational speed. The microspheres were dispersed in the solution of immunomodulatory peptide DP7-C/miR-26a complex to prepare drug-loaded microspheres. The physical properties of the microspheres were characterized. The best drug-loaded porous poly(lactic-co-glycolic acid) microspheres were selected by comparing productivity, encapsulation rate and release performance for further use. (2) In vitro cell experiment: Drug-loaded and drug-free microsphere solutions with different mass concentrations were co-cultured with rat bone marrow mesenchymal stem cells. CCK-8 assay was performed to verify biocompatibility. (3) Animal in vivo experiment: Nine adult Sprague-Dawley rats were randomly divided into blank group, control group and experimental group, with three rats in each group. Cranial defect models with a diameter of 5 mm were established in all three groups. The rats of the blank group were not implanted with the material. The rats of the control group were implanted with blank microspheres. The rats of the experimental group were implanted with microspheres loaded with DP7-C/miR-26a complex. At 8 weeks after operation, the pathological morphology and immunohistochemical staining for alkaline phosphatase of the main organs and skull defects were performed. 
    RESULTS AND CONCLUSION: (1) Microsphere preparation: According to the relevant detection results, the drug-loaded microspheres prepared at 1 000 r/min compared with 500 and 1 200 r/min had uniform size, higher yield and better sustained release performance, which could be used in subsequent experiments. (2) In vitro cell experiment: CCK-8 assay results exhibited that drug-loaded and drug-free microsphere solutions had no effect on the proliferation of bone marrow mesenchymal stem cells and had no obvious cytotoxicity. (3) In vivo experiments: There were no pathological changes in the viscera on hematoxylin-eosin staining related to the treatment with the intervention. Hematoxylin-eosin staining and Masson staining demonstrated that in the blank group, the defect site was mainly filled by fibrous connective tissue, with a small amount of angiogenesis, but without obvious new bone formation. In the control group, a small amount of new bone formation, fibrous tissue hyperplasia and new capillaries could be visible at the defect site. In the experimental group, there was obvious new bone formation, different degrees of fibrous tissue hyperplasia and new capillaries in the defect area. Immunohistochemical results displayed that alkaline phosphatase was highly expressed in the experimental group compared to the blank group and the control group (P < 0.05). (4) These findings have concluded that the porous poly(lactic-co-glycolic acid)/DP7-C/miR-26a composite system has good biocompatibility and in vivo osteogenic properties and can promote bone regeneration and repair of critical bone defects in the rat skull. 
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    An injectable dextran/gelatin composite hydrogel loaded with exosomes for repair of rat intervertebral disc degeneration
    Pan Yujun, Shi Changjiang, Cao Sheng, Mu Huaizhao, Zhang Yilong, Wang Kaihua
    2023, 27 (34):  5477-5482.  doi: 10.12307/2023.554
    Abstract ( 282 )   PDF (1368KB) ( 164 )   Save
    BACKGROUND: Exosomes can improve the inflammatory microenvironment of the degenerated intervertebral disc. However, direct injection of exosomes into the degenerated intervertebral disc at local concentrations and transient release cannot guarantee sustained effects, so the in vivo therapeutic effect of exosomes alone is limited. 
    OBJECTIVE: To observe the effect of exosome-loaded glucan/gelatin composite hydrogel on repairing rat degenerative intervertebral disc. 
    METHODS: Exosomes were extracted from bone marrow mesenchymal stem cells of rats. Exosome-loaded dextran/gelatin composite hydrogels were prepared by Schiff crosslinking reaction, and the microstructure and elastic modulus of the hydrogels were detected. Sixty Sprague-Dawley rats were randomly divided into five groups, with 12 rats in each group. Group A was the normal control. In groups B, C, D, and E, the intervertebral disc degeneration model was established by percutaneous puncture. PBS, exosomes, glucan/gelatin composite hydrogel and exosome-loaded glucan/gelatin composite hydrogel were injected into the intervertebral disc in turn. At postoperative 8 weeks, imaging, histopathology and western blot assay were performed.
    RESULTS AND CONCLUSION: (1) The exosome-loaded glucan/gelatin composite hydrogels presented a three-dimensional porous structure with interconnected pores. The pore size was 50-200 μm, and the elastic modulus was (4.41±0.23) kPa, respectively. The exosomes could be released continuously and stably in vitro for more than 20 days. (2) At 8 weeks after operation, X-ray films exhibited that the intervertebral disc height index percentages of rats in groups B-E were lower than those in group A (P < 0.05). The intervertebral disc height index percentages of rats in groups C, D and E were higher than those in group B 
    (P < 0.05), of which group E was the most obvious. At 8 weeks after operation, MRI examination showed compared with group A, the tissue structure of nucleus pulposus in groups B-E was damaged to different degrees. Compared with group B, the tissue structure of nucleus pulposus in groups C-E was improved to varying degrees, among which group E had the most obvious improvement. (3) Hematoxylin-eosin staining and saffron O staining at 8 weeks after surgery exhibited that the structure of the nucleus pulposus in group B was severely damaged and only contained a small amount of collagen. Compared with group B, the structure of nucleus pulposus in groups C-E was improved, and the structure of nucleus pulposus in group E was finer, clearer, regular and had the most collagen content. (4) Western blot assay demonstrated that compared with group A, the expression levels of type II collagen and proteoglycan protein in groups B-E were decreased (P < 0.05). Compared with group B, the expression levels of type II collagen and proteoglycan protein in groups C-E were increased (P < 0.05), and those in group E were the most obvious. (5) It is concluded that the dextran/gelatin composite hydrogel loaded with exosomes injected into the degenerative intervertebral disc can restore the intervertebral disc height and intervertebral disc signal intensity, restore the tissue structure, and delay intervertebral disc degeneration to a certain extent.
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    Collagen/silk fibroin scaffold combined with human umbilical cord-derived mesenchymal stem cells in the treatment of traumatic brain injury in dogs
    Wang Ziqi, Li Xiaoyin, Jiang Jipeng, Song Zhen, Li Zhengchao, Chen Shulian, Chen Xuyi
    2023, 27 (34):  5483-5490.  doi: 10.12307/2023.725
    Abstract ( 251 )   PDF (4097KB) ( 128 )   Save
    BACKGROUND: So far, the subversive treatment of traumatic brain injury is very limited. The combination of medicine and engineering has brought new prospects for the repair and regeneration of central nervous system nerves.  
    OBJECTIVE: To investigate the therapeutic effect of collagen/silk fibroin scaffold that can carry seed cells and is safe and porous, combined with human umbilical cord-derived mesenchymal stem cells on traumatic brain injury in beagle dogs.
    METHODS: (1) Passage 3 human umbilical cord-derived mesenchymal stem cells were inoculated onto collagen/silk fibroin scaffold. The growth of human umbilical cord-derived mesenchymal stem cells was observed by inverted phase contrast microscope, scanning electron microscope, immunofluorescence staining and hematoxylin-eosin staining. (2) Twenty-four beagle dogs were randomly divided into four groups. In the trauma group, only the traumatic brain injury model was established without other treatment. In the stem cell group, human umbilical cord-derived mesenchymal stem cells were transplanted after model establishment. In the scaffold group, the collagen/silk fibroin scaffold was transplanted after model establishment. In the combination group, human umbilical cord-derived mesenchymal stem cells and collagen/silk fibroin scaffold were transplanted after model establishment. The grafts were all transplanted locally in the injured area. At 1 day, 1, 4, 8, 12, 16, 20 and 24 weeks after operation, a modified Glasgow Coma Scale was performed respectively. Motor-evoked potentials were detected at 1, 3 and 6 months after operation. At 6 months after operation, magnetic resonance imaging and in situ hybridization of brain tissue repair RNA were performed to evaluate the recovery of traumatic brain injury.  
    RESULTS AND CONCLUSION: (1) Human umbilical cord-derived mesenchymal stem cells attached to collagen/silk fibroin scaffold surface grew well and extended many pseudopods. (2) Modified Glasgow Coma Scale score of the combination group was significantly higher than that of the trauma group, stem cell group and scaffold group at 1, 4, 8, 12, 16, 20 and 24 weeks after operation (P < 0.05). (3) The latency and amplitude of motor-evoked potential of the combination group at 1, 3 and 6 months were significantly better than those of the trauma group under different constant pressure stimuli (P < 0.01). (4) Diffusion tensor imaging of magnetic resonance scanning showed that the integrity of the corticospinal tract in the combination group was better than that in the trauma, stem cell and scaffold groups, and a new corticospinal tract could be seen on the injured side. (5) The results of in situ hybridization of brain tissue repair RNA demonstrated that the expression levels of synaptophysin, microtubule-associated protein 2, von Willebrand factor, neurofilament protein and MBP in the combination group were more than those in the trauma, stem cell and scaffold groups. (6) It is indicated that human umbilical cord-derived mesenchymal stem cells combined with collagen/silk fibroin scaffold play an active role in corticospinal tract regeneration, motor function recovery, angiogenesis and neurite growth in dogs with traumatic brain injury.
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    Construction of tissue-engineered bone composite scaffolds by loading rabbit-derived bone marrow mesenchymal stem cells on magnesium-based alloy scaffolds
    Zhou Yuebin, Guo Honggang
    2023, 27 (34):  5491-5496.  doi: 10.12307/2023.726
    Abstract ( 217 )   PDF (1464KB) ( 66 )   Save
    BACKGROUND: With the in-depth research and rapid development of tissue engineering, tissue-engineered scaffolds provide a new opportunity for bone tissue repair.  
    OBJECTIVE: To explore the cell proliferation of bone marrow mesenchymal stem cells after co-culture with the magnesium-based alloy scaffolds, to provide a new idea for the construction of tissue-engineered bone scaffolds and provide a basis for the clinical application of tissue-engineered scaffolds.
    METHODS: The bone marrow fluid of rabbits was extracted under sterile conditions. Bone marrow mesenchymal stem cells were cultured and isolated by the whole bone marrow adherent method. Bone marrow mesenchymal stem cells were identified by flow cytometry and osteogenic differentiation ability was tested. Bone marrow mesenchymal stem cells at passage 3 were seeded on magnesium-based alloy scaffolds and chitosan polycaprolactone tricalcium phosphate scaffolds respectively. The cell growth was observed by laser confocal scanning on days 3 and 10, and cell proliferation was detected using an MTT assay on days 1, 4, 7, 10 and 14, respectively.  
    RESULTS AND CONCLUSION: (1) The cultured cells highly expressed CD44 and CD90, but hardly CD34. (2) The morphology gradually changed to polygonal after osteogenesis induction. Von Kossa staining showed that the calcium nodules between the cells were stained black, and the alkaline phosphatase activity was significantly higher than that of the control group (P < 0.05). (3) After co-culture of magnesium-based alloy and bone marrow mesenchymal stem cells, confocal scanning showed that the cells could adhere to the scaffold and grow in clusters. With the extension of time, the magnesium-based alloy scaffold was more active in proliferation than the seed cells loaded on the chitosan polycaprolactone tricalcium phosphate scaffold, and the number of cells was significantly increased. MTT assay showed that when the two materials were co-cultured with bone marrow mesenchymal stem cells for 10 days, the cell growth reached its peak. (4) These results indicate that rabbit-derived bone marrow mesenchymal stem cells have a good osteogenic potential. After co-cultured with magnesium-based alloy scaffolds, the cells adhered and grew well on the surface of the scaffolds, indicating that the tissue-engineered magnesium-based implants were successfully constructed.
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    Biosafety evaluation of poly(lactic acid)/nano-hydroxyapatite composite microspheres
    Zhao Kang, Lin Si, Ge Xiaotian, Du Xinrui, Han Yingchao
    2023, 27 (34):  5497-5504.  doi: 10.12307/2023.808
    Abstract ( 375 )   PDF (1602KB) ( 37 )   Save
    BACKGROUND: As nanomaterials and medical devices containing nanomaterials have unique characteristics such as small size and large specific surface area, which may lead to special biological effects, their biological safety has become the focus of attention. 
    OBJECTIVE: To evaluate the biosafety of poly(lactic acid)/nano-hydroxyapatite composite microspheres.
    METHODS: Poly(lactic acid)/nano-hydroxyapatite composite microspheres were prepared by emulsion solvent evaporation. (1) Cytotoxicity test: Mouse fibroblasts were co-cultured with poly(lactic acid)/nano-hydroxyapatite composite microspheres extract. Blank control (complete medium), negative control (high-density polyethylene resin extract) and positive control (zinc diethyldithiocarbamate extract) were set. The cytotoxicity was evaluated by MTT assay. (2) Sensitization reaction: Polar and non-polar extraction of the sample, intradermal induction and excitation test were conducted, and the results were recorded. (3) Intradermal reaction: Polar extraction and non-polar extraction of composite microspheres were performed. Immediately, 24, 48 and 72 hours after intradermal injection, the status of each injection site was observed. (4) Acute systemic toxicity: The composite microspheres were extracted by polar extraction and non-polar extraction. After intravenous and intraperitoneal injection into the body of KM mice, the changes in body weight of mice were observed. (5) Pyrogen reaction: After polar extraction, the composite microspheres were injected through the ear vein into the rabbit to record changes in body temperature. (6) Bone implantation test: Cylindrical composite microspheres with high-density polyethylene rods were implanted into the tibial defects of rabbits for gross observation and local histopathological observation. 
    RESULTS AND CONCLUSION: (1) The poly(lactic acid)/nano-hydroxyapatite composite microspheres had no cytotoxicity, sensitization, intradermal irritation, or acute systemic toxicity. The pyrogen reaction was in line with the test regulations. After the composite microspheres were implanted into the tibial defect of rabbits, no lesions such as hematoma, edema or inflammation were observed at the implantation site, and the histological observation showed that the composite microspheres had a certain ability of bone tissue repair. (2) Bone results show that poly(lactic acid)/nano-hydroxyapatite composite microspheres had good biosafety. 
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    Application value of environment-friendly tissue sample preparation solution in the detection of different adipocytes
    Chen Hongcai, Wang Shaohong, Wang Yuanyuan, Gu Jiamei, Liu Chunpeng, Zhao Yongqiang, Qiu Xiaoyang, Zhan Xiaofen
    2023, 27 (34):  5510-5515.  doi: 10.12307/2023.715
    Abstract ( 208 )   PDF (1228KB) ( 77 )   Save
    BACKGROUND: The quality of conventional paraffin sections prepared by traditional reagents (formaldehyde solution fixation, ethanol dehydration, xylene transparent dewaxing) used for tissue pretreatment is low, which has become the bottleneck of pathological diagnosis of adipocytic tumors. Moreover, traditional reagents are easy to pollute the laboratory environment and cause various health hazards to laboratory personnel.
    OBJECTIVE: To explore the application value of environmental friendly tissue sample preparation solution in the detection of MDM2 gene in adipocyte-tumor hematoxylin-eosin staining and atypical lipomatous-tumor/well differentiated liposarcoma.
    METHODS: From February 2016 to July 2022, 592 samples of adipocyte tumors were selected as the research objects. The same sample was cut in half. According to the different reagents used in the pretreatment of samples, they were randomly divided into two groups: the traditional group and the environmental protection group. In the traditional group, 592 conventional paraffin sections were made by formalin fixation, alcohol dehydration and xylene transparent dewaxing. In the environmental protection group, 592 slices were made with environmental protection tissue sample preparation solution. According to the different grades of hematoxylin-eosin staining quality of sections, the excellent and good rate of the matoxylin-eosin staining was compared between the two groups. Further, 33 specimens of atypical lipomatous tumor/well differentiated liposarcoma confirmed by pathology were sectioned again, and the MDM2 gene was detected by fluorescence in situ hybridization to compare the difference in the amplification rate of MDM2 gene between the two groups.
    RESULTS AND CONCLUSION: (1) Compared with the traditional group, the tissue sections of the adipocyte tumors in the environmental protection group were more stretched and complete; the cells were not folded; the staining was clearer; the red blue contrast was better and the cell structure was denser. (2) The excellent and good rate of hematoxylin-eosin staining of tissue sections in the environmental protection group was higher than that in the traditional group, with a statistically significant difference (P=0.000). (3) Compared with the traditional group, the MDM2 probe and the CSP12 probe of the environmental protection group bound only in the specific region of the sample chromosome, which was more specific. (4) The number of successfully hybridized cells in the environmental protection group was higher than that in the traditional group, and the difference was statistically significant (P=0.000). (5) There was no significant difference in MDM2 gene signal number, MDM2/cell value, CSP12 signal number, CSP12/cell value and MDM2/CSP12 value between the traditional group and the environmental protection group (P > 0.05). (6) There was no significant difference in the amplification rate of MDM2 gene between the two groups (P=0.31). (7) The results showed that the environment-friendly tissue sample preparation solution is conducive to improving the excellent and good rate of hematoxylin-eosin staining of adipocyte tumors and ensuring the detection quality of MDM2 gene in atypical lipomatous tumors/well differentiated liposarcomas and has the value of clinical promotion. 
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    Disposal methods of allografts affect bone remodeling at the tendon-bone healing interface after canine anterior cruciate ligament reconstruction
    Shang Xiaoke, Ma Zhanjun, Wen Peng, Wang Hao, Ma Shaowei, Hu Jianzhong, Li Jian, Zheng Jun, Li Qi
    2023, 27 (34):  5516-5522.  doi: 10.12307/2023.882
    Abstract ( 202 )   PDF (1202KB) ( 166 )   Save
    BACKGROUND: The process of tendon-bone healing after anterior cruciate ligament reconstruction with allografts is complex, and tunnel enlargement may occur due to poor healing. The process of preoperative graft treatment may have some influence on tendon-bone healing, but the specific situation is not clear.
    OBJECTIVE: To explore the effects of allograft disposal methods on bone remodeling during tendon-bone healing after anterior cruciate ligament reconstruction surgery. 
    METHODS: Thirty-two male beagles were randomly divided into four groups (n=8 per group) for anterior cruciate ligament reconstruction by coin toss method after establishing bilateral posterior cruciate ligament rupture models. In group A, fresh autogenous Achilles tendon grafts were used. In group B, a fresh allograft Achilles tendon was used. In group C, an allograft Achilles tendon irradiated by gamma rays and refrigerated at low temperature was used. In group D, lyophilized allograft tendon after γ-ray irradiation was used. Micro CT scanning and osteoclast tartrate-resistant acid phosphatase staining were performed in the femor-graft-tibia complex at 3 and 6 months after anterior cruciate ligament reconstruction. Scanning images were selected to measure the bone microstructural parameters and a 3D bone tunnel model was established to measure the tunnel area.
    RESULTS AND CONCLUSION: (1) Micro CT scan: 3 months after operation, the connection density, trabecular number, trabecular thickness, ratio of bone volume to total volume and structural model index in group D were lower than those in groups A and C (P < 0.05). The trabecular separation was higher in group D than that of group A (P < 0.05). The connection density, trabecular number and structural model index of group B were lower than those of group A (P < 0.05). The trabecular separation was higher in group B than that in group A (P < 0.05). The ratio of bone volume to total volume was lower in group B than that in groups A and C (P < 0.05). Six months after surgery, the connection density, trabecular number and the ratio of bone volume to total volume in group D were lower than those in group A (P < 0.05). Trabecular thickness and structural model index were lower in group D than those in groups A and C (P < 0.05). The trabecular separation was higher in group D than that in group A (P < 0.05). The connection density and structural model index of group B were lower than those of group A (P < 0.05). The trabecular thickness was lower in group B than that in groups A and C (P < 0.05). The trabecular separation was higher in group B than that in group A (P < 0.05). (2) Tartrate-resistant acid phosphatase staining: Compared with group A, osteoclasts in groups B and D were stained more deeply and more in number. The osteoclasts in group C were similar to those in group A in morphology and quantity, with small volume and light staining. (3) Tunnel area: At the same time point, the tunnel expansion of the femur and tibia in group D was the largest. The area of the inner opening of the tibial tunnel at 3 months after operation and the area of the inner opening and middle part of the femoral tunnel at 3 and 6 months after operation in group B were larger than that in group A (P < 0.05). The area of the inner opening of the tibial tunnel at 3 and 6 months after operation was larger than that of group A (P < 0.05). (4) Those findings suggest that bone tunnel enlargement is common during tendon-bone healing after anterior cruciate ligament reconstruction. The disposal methods may affect bone resorption and the changes in bone microstructure mediated by osteoclasts at the tendon-bone interface. Therefore, it affected bone remodeling during tendon-bone healing.
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    Biomechanical analysis of unilateral biportal endoscopic lumbar interbody fusion
    Li Jiarui, Yan Yang, Wu Xiaogang, Feng Haoyu, He Liming
    2023, 27 (34):  5523-5529.  doi: 10.12307/2023.739
    Abstract ( 316 )   PDF (1526KB) ( 102 )   Save
    BACKGROUND: Unilateral biportal endoscopic lumbar interbody fusion as a novel minimally invasive technique has been widely used in the treatment of lumbar degenerative diseases. However, as a postoperative complication, fusion cage subsidence cannot be completely avoided.  
    OBJECTIVE: To analyze the biomechanical characteristics of unilateral biportal endoscopic lumbar interbody fusion technology by establishing a finite element model, as well as the risk of fusion cage subsidence under different heights of the fusion cage and osteoporosis conditions.
    METHODS: Based on the CT data of healthy adult male volunteers, the finite element models of the L4-L5 vertebral body were constructed. According to the unilateral biportal endoscopic lumbar interbody fusion operation method, the models with different cage heights of 8, 10 and 12 mm were successively constructed (normal bone and osteoporosis). The flexion, extension, right lateral bend, left lateral bend, right axial rotation, and left axial rotation motions were simulated in models with different bone conditions on the upper surface of L4 with 500 N follower-load and 10 Nm torsional torque. The range of motion, pedicle screw-rod system stress and endplate stress of each model under different working conditions were observed and analyzed. 
    RESULTS AND CONCLUSION: (1) Under the same motion state, the range of motion of the six kinds of lumbar fusion models was significantly lower than that of the normal lumbar model. The range of motion of six kinds of interbody fusion models was the largest under flexion and the smallest under extension. With the increase in cage height, the range of motion of the intervertebral fusion model decreased under the same bone and motion conditions. (2) Under the same bone and motion conditions, with the increase in cage height, the stress of the pedicle screw rod system of interbody fusion model decreased. The stress of pedicle screw rod system in six kinds of interbody fusion models was the highest under lateral bending movement and the lowest under flexion and extension. When the height of the fusion cage was the same, the stress of the pedicle screw rod system in the osteoporosis model was greater than that in the normal model. (3) Under the same bone and motion conditions, with the increase of cage height, the maximum stress of the L4 lower endplate (or L5 upper endplate) of the intervertebral fusion model increased. When the height of the fusion cage was the same, the maximum stress of the L4 lower endplate (or L5 upper endplate) in the osteoporosis model was slightly greater than that in the normal model. Under the same motion state, the maximum stress of the L4 lower endplate was greater than that of the L5 upper endplate in six kinds of intervertebral fusion models. The maximum stress of the L4 lower endplate (or L5 upper endplate) under the flexion was the largest and the maximum stress of the L4 lower endplate (or L5 upper endplate) under the extension was the smallest. (4) The results show that the higher the fusion cage is, the better it is, but it needs to be properly stretched to ensure the stability of the segment and avoid the increased risk of fusion cage subsidence caused by too high fusion cage.
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    Role of cuproptosis regulator in diagnosis and subtype of osteoarthritis
    Xiong Bo, Wang Bin, Liu Jinfu, Lu Guanyu, Chen Cai, Huang Yue, Chen Lihua
    2023, 27 (34):  5530-5537.  doi: 10.12307/2023.702
    Abstract ( 295 )   PDF (2018KB) ( 50 )   Save
    BACKGROUND: Synovium plays an important role in the development of osteoarthritis, and cuproptosis is a new type of programmed cell death recently discovered, up to now, there is no research on the mechanism of cuproptosis gene in osteoarthritis from synovial angle.  
    OBJECTIVE: The synovial membrane was used as the entry point to explore the potential mechanism of the development of osteoarthritis from the perspective of cuproptosis.
    METHODS: The coincident osteoarthritis related chips were retrieved through Gene Expression Omnibus (GEO) database and standardized. Cuproptosis related genes were extracted and quantified based on the gene expression matrix after treatment. Random Forest model, Support Vector Machines model, Machine learning and Nomogram Model were used to construct disease prediction model to predict the risk of osteoarthritis. Then, consensus clustering algorithm, principal component analysis, single sample gene set enrichment analysis and immune infiltration were used to analyze the correlation of cuproptosis molecular subtypes with immune microenvironment and inflammatory factors.  
    RESULTS AND CONCLUSION: (1) A risk prediction model based on cuproptosis characteristic gene was established for the first time. The disease prediction model constructed by three cuproptosis characteristic genes (DBT, LIPT1, FDX1) could predict the risk of osteoarthritis. (2) It is found for the first time that patients with osteoarthritis can be classified into two distinct subtypes of cuproptosis molecule (cluster A and cluster B). Cluster B is highly correlated with the imbalance of Th1/Th2 cell ratio, and has higher expression levels of interleukin-2, interleukin-4, and interleukin-5.
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    Mechanism and application of glycosaminoglycan in bone tissue engineering
    You Yan, Chen Jiawen, Lin Binbin, Wu Jingyi, Liu Peng, Wu Buling, Sun Tianyu
    2023, 27 (34):  5538-5545.  doi: 10.12307/2023.835
    Abstract ( 390 )   PDF (1025KB) ( 71 )   Save
    BACKGROUND: The repair of complex bone defects remains a worldwide public health issue. Currently, utilizing biofunctionalized tissue engineering materials to achieve bone regeneration has been an important research focus. Previous studies on the biochemical repair of bone tissue focused on the exploration of intracellular signaling regulatory networks, while the modification and regulation of extracellular signaling molecules were less studied. The modification of glycosaminoglycans as important signaling molecules in the extracellular matrix to play an osteogenic role in scaffold materials is an emerging research direction.
    OBJECTIVE: To review the mechanism and application of glycosaminoglycan in bone tissue engineering.
    METHODS: PubMed and CNKI databases were searched for articles concerning glycosaminoglycans to regulate bone tissue regeneration and repair and its role and functional application in bone tissue engineering with the search terms “glycosaminoglycans, proteoglycans, bone tissue engineering, bone tissue engineering materials, osteogenic differentiation” in English and Chinese respectively. After primarily screening based on the inclusion and exclusion criteria, 
    85 articles with high quality and relevance were included for review. 
    RESULTS AND CONCLUSION: (1) As an important component of the extracellular matrix, glycosaminoglycan not only binds to growth factors to facilitate their diffusion, but also promotes the interaction between receptors and ligands to regulate the signaling pathway of bone regeneration. (2) In bone tissue engineering, glycosaminoglycans are chemically modified and cross-linked, or co-modified with other natural or synthetic polymers in cell scaffolds to support cell adhesion and proliferation, and serve as signaling molecules to provide binding sites for growth factors to stabilize growth factors and promote the binding of endogenous and exogenous growth factors to their corresponding receptors, which can achieve effective bone tissue regeneration. (3) There are still many unresolved issues regarding the application of glycosaminoglycans in bone tissue engineering, such as the form and safety of the local long-term application of glycosaminoglycan, the exact mechanism of action on the fate of osteoblasts, synthesis and purification, which needs to be further improved. 
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    Natural small molecular compounds in the treatment of bone-related diseases by regulating type H blood vessels and its application in tissue engineering
    Xu Zhengyi, Wan Qianbing, Chen Junyu
    2023, 27 (34):  5546-5553.  doi: 10.12307/2023.560
    Abstract ( 317 )   PDF (1065KB) ( 49 )   Save
    BACKGROUND: Type H blood vessels, a specific subtype of vessels newly discovered in recent years, have been identified to couple angiogenesis and osteogenesis. They play an important role in the physiological and pathological processes of the skeletal system. Natural small molecular compounds have the advantages of widespread sources, low toxic and side effects. In recent years, studies have found that natural small molecular compounds can regulate type H blood vessels. 
    OBJECTIVE: To review the basic characteristics of type H blood vessels and discuss the application status and prospect of several natural small molecular compounds in the treatment of bone-related diseases. 
    METHODS: The literature search was performed in Web of Science, PubMed, CNKI and WanFang databases. Relevant articles published from January 2014 to June 2022 were researched with the key words of “type H vessel, natural small molecular compounds, natural small molecule drugs, active ingredients of traditional Chinese medicine” in Chinese and “type H vessel, H-type vessel, type H microvessel, type H blood vessel, CD31hiEmcnhi endothelial cell, CD31hiEndomucinhi blood vessel, CD31(hi)Emcn(hi) endothelial cell, specific vessel subtype, natural small molecular compounds, Chinese medicine, Chinese traditional medicine, Chinese plant extracts” in English. After reading the titles and abstracts, repetitive studies, low-quality or irrelevant articles were excluded. Finally, 65 articles were included for review.
    RESULTS AND CONCLUSION: (1) Type H vessel is a special subtype of blood vessels mainly found in the metaphysis and endosteum of long bones, and also exist in other types of bones. At most sites, type H vessels are arranged linearly with a distinctive columnar or palisade-like structure. Moreover, type H blood vessels have significant age-related changes in length and abundance of vascular buds. (2) Type H vessels play an important role in couple angiogenic and osteogenic processes via blood flow as well as the recruitment and regulation of osteoblasts lineage and osteoclast lineage. (3) Type H vessels are important in the occurrence and development of bone disease. Natural small molecular compounds show a good prospect in the study of treating bone-related diseases including osteoarthritis, osteoporosis, bone fracture, and unloading-induced bone loss via regulating type H blood vessels. For example, diterbutyl phthalate, the extract of Panax notoginseng, blunted the aberrant formation of type H vessels to prevent osteoarthritis progression. Ginsenoside compound K, the extract of Panax ginseng, can promote the formation of type H vessels in callus and accelerate fracture healing. (4) In view of the prospective effect of tissue engineering scaffolds loading drugs and cytokines on type H blood vessels in the treatment of bone diseases and natural small molecular compounds in regulating type H blood vessels, the combination of tissue engineering scaffolds and natural small molecular compounds to regulate type H blood vessels is a potential strategy.
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    Application of platelet-rich plasma combined with electrospun nanoscaffolds in bone and soft tissue
    Zhao Mingyue, Yang Shun, Tu Xiling, Gao Li, Yang Kun, Liu Qi
    2023, 27 (34):  5554-5560.  doi: 10.12307/2023.502
    Abstract ( 268 )   PDF (964KB) ( 32 )   Save
    BACKGROUND: Both electrospinning and platelet-rich plasma have shown great application prospects in tissue regeneration and repair, but there are few studies on electrospun nanofiber composite scaffolds loaded with platelet-rich plasma.
    OBJECTIVE: To review the research progress of electrospun nanofiber composite scaffolds loaded with platelet-rich plasma in bone and soft tissue engineering in recent years, in order to provide ideas and theoretical support for further in-depth research on the clinical application of composite scaffolds.
    METHODS: Using “tissue engineering, platelet-rich plasma, electrospun scaffolds, stem cell, regenerative medicine” as English search terms and “tissue engineering, platelet-rich plasma, electrospinning, stem cell, tissue regeneration, bone regeneration, cartilage regeneration, soft tissue regeneration” as Chinese search terms, we searched PubMed, Web of Science, Ovid, SpringerLink, Wiley Oline Library, Medline, Wanfang, and CNKI databases. Totally 64 articles were finally included for review.
    RESULTS AND CONCLUSION: (1) Electrospun nanoscaffolds loaded with platelet-rich plasma have the advantages of both platelet-rich plasma and electrospun nanoscaffolds, which are more elastic, less tearing, suitable mechanical strength and good biocompatibility. (2) The combination of platelet-rich plasma and three-dimensional oriented fiber scaffolds can better simulate the microenvironment of natural tissues, promote cell growth, proliferation and differentiation, and promote bone and soft tissue repair and regeneration. (3) In terms of bone tissue regeneration, it has certain compressive capacity under different stress conditions, and has good cell compatibility. (4) In terms of soft tissue regeneration, by regulating the porosity and surface area of the material, it is beneficial to cell respiration, and can promote wound healing, nerve cell growth and vascular regeneration. (5) However, due to various reasons, there are still few ideal materials that can be used in clinical practice to promote the regeneration and repair of bone and soft tissue. How to make use of the advantages of various materials and how to optimize the physical and chemical properties of various materials, so as to strengthen the interaction between scaffolds and seed cells, and maintain a high sustained-release effect on platelet-rich plasma-derived growth factor remains one of the problems to be solved in future research, which needs further in vivo research and clinical trials. 
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    Signaling pathway of osteoblast autophagy in periprosthetic osteolysis
    Gu Yingchu, Gu Ye, Wu Zerui, Fang Tao, Wang Qiufei, Chen Bingqian, Peng Yuqin, Geng Dechun, Xu Yaozeng
    2023, 27 (34):  5561-5569.  doi: 10.12307/2023.717
    Abstract ( 338 )   PDF (1186KB) ( 64 )   Save
    BACKGROUND: Recent evidence suggests that autophagy, as a cell self-protection mechanism, plays an important role in regulating osteoblast function and maintaining osteoblast homeostasis. It has an important influence on the treatment and prognosis of periprosthetic osteolysis.
    OBJECTIVE: To provide new therapeutic ideas and potential therapeutic targets for periprosthetic osteolysis by summarizing previous studies on the autophagy mechanism of osteoblasts.
    METHODS: The first author used the computer to search the articles published from 2015 to 2022. In Chinese, the search terms “wear particles, periprosthetic osteolysis, osteoblasts, signal pathways, autophagy” were used to search the databases of CNKI, WanFang, and VIP. In English, the PubMed and Web of Science databases were retrieved with “wear debris, wear particles, peri*prosthetic osteolysis, PPOL, aseptic loosening, osteoblast, OB, signal path, autophagy”. A total of 98 articles were included according to the inclusion criteria.  
    RESULTS AND CONCLUSION: (1) In periprosthetic osteolysis, the changes in the autophagy ability of osteoblasts induced by wear particles play a key role in the development and outcome of the disease. (2) A variety of signaling pathways jointly mediate autophagy in osteoblasts, among which the key pathways include AMPK/ULK1/mTOR, nuclear factor-κB, Pink1/Parkin, etc. AMPK, mTOR, and ULK1 can regulate each other and jointly maintain the stability of the autophagy level. There is a complex crosstalk between the nuclear factor-κB pathway and autophagy. PINK1 and Parkin are accumulated on the surface of the damaged mitochondrial membrane, inducing autophagy. (3) There is crosstalk among multiple signaling pathways, which form a complex autophagy network under their mutual influence. Moreover, the activation of the same autophagy pathway in different cells may bring about completely opposite effects. (4) Moderate autophagy induced by wear particles can reduce the apoptosis of osteoblasts, enhance their differentiation and mineralization ability, and improve the prognosis of osteolysis around the prosthesis. On the contrary, insufficient or excessive activation of autophagy will cause damage to osteoblasts and promote the progress of osteolysis. Therefore, targeting the level of autophagy of osteoblasts induced by wear particles through drugs or genes may be one of the directions for the treatment of periprosthetic osteolysis. 
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    Manganese-containing bioceramic materials in the field of bone repair
    Wang Xinjie, Wang Guodong, Zheng Zhongren, Shao Yiming, Wang Jialiang, Ma Hui, Zhao Xiaowei
    2023, 27 (34):  5570-5576.  doi: 10.12307/2023.887
    Abstract ( 300 )   PDF (958KB) ( 126 )   Save
    BACKGROUND: Based on the superior properties of ceramics, bioceramic materials are widely used in bone transplantation and tissue engineering. However, it still faces the problems of low mechanical strength and single biological function, which cannot fully meet the clinical application of bone defect repair.  
    OBJECTIVE: To summarize the research status of bioceramic scaffolds and the effect of manganese doping on the performance of ceramics. 
    METHODS: Chinese and English search terms were “manganese, microelements, ceramic biomaterials, hydroxyapatite, tricalcium phosphate, 3D printing, bone tissue engineering”. Searches were carried out on CNKI, WanFang, PubMed, and Web of Science databases. Relevant articles published from January 1968 to September 2022 were retrieved. According to the inclusion criteria, 84 articles were finally included.  
    RESULTS AND CONCLUSION: Manganese, as an important locally delivering therapeutically active ion, has a positive stimulating effect on cell function and bone formation. (1) The doping of manganese elements can greatly improve the mechanical properties of ceramic scaffolds, further enhance the osteogenic induction ability of ceramic materials, and endow the scaffolds with additional antibacterial properties. (2) Based on manganese-containing bioceramics, the need for bone defect repair was further met through coating, covalently binding bioactive peptides and regulating the valence of doping elements. (3) It began to gradually change from single-element doping to multi-element doping, and strive to give the stent more characteristics. (4) Doping of manganese elements is an effective modification treatment method. Manganese-containing bioceramics have a good application prospect in the repair of fractures and bone defects by combining advanced material manufacturing technology and the excellent biological activity of manganese.
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