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    08 October 2025, Volume 29 Issue 28 Previous Issue    Next Issue
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    In vitro angiogenesis and osteogenesis properties of copper-doped mesoporous bioactive glass
    Zeng Yu, Xie Chengwei, Hong Yuanqi, Su Shenghui, Dong Xieping
    2025, 29 (28):  5941-5949.  doi: 10.12307/2025.472
    Abstract ( 220 )   PDF (2409KB) ( 136 )   Save
    BACKGROUND: Mesoporous bioactive glass has great application potential in bone repair due to its excellent biocompatibility and osteoinductive activity. Incorporating therapeutic ions into mesoporous bioactive glass particles can give the material more ideal biological properties.
    OBJECTIVE: To synthesize copper-doped mesoporous bioactive glass and investigate its in vitro angiogenesis and osteogenic differentiation properties.
    METHODS: Mesoporous bioactive glass and copper-doped mesoporous bioactive glass were synthesized by microemulsion-assisted sol-gel method. The morphology, structure, composition, and ion release performance of the materials were characterized by scanning electron microscopy, transmission electron microscopy, energy dispersive spectroscopy, and X-ray diffraction. The extracts of mesoporous bioactive glass and copper-doped mesoporous bioactive glass were co-cultured with mouse fibroblasts L929. Biocompatibility of the materials was evaluated by live/dead staining and CCK-8 assay. The extracts of the two materials were co-cultured with human umbilical vein endothelial cells. The angiogenesis-promoting properties of the materials were evaluated by Transwell assay, scratch assay, and CD31 immunofluorescence staining. The extracts of the two materials were co-cultured with mouse bone marrow mesenchymal stem cells. The osteogenic properties of the materials were evaluated by alkaline phosphatase staining (without osteogenic induction solution) and Alizarin red staining (with osteogenic induction solution).
    RESULTS AND CONCLUSION: (1) The characterization results exhibited that both mesoporous bioactive glass and copper-doped mesoporous bioactive glass presented a tightly packed granular morphology with similar internal mesoporous structures, and copper-doped mesoporous bioactive glass could continuously release copper ions. (2) The live/dead staining and CCK-8 assay results showed that compared with mesoporous bioactive glass, copper-doped mesoporous bioactive glass could promote the proliferation of L929 cells and had good biocompatibility. (3) The results of Transwell assay, scratch assay, and CD31 immunofluorescence staining exhibited that compared with mesoporous bioactive glass, copper-doped mesoporous bioactive glass could promote the migration of human umbilical vein endothelial cells and the expression of CD31 protein, and promote angiogenesis. (4) The results of alkaline phosphatase staining and alizarin red staining demonstrated that the osteogenic performance of copper-doped mesoporous bioactive glass was stronger than that of mesoporous bioactive glass. The results indicate that copper-doped mesoporous bioactive glass has excellent biocompatibility and the potential to promote angiogenesis and bone regeneration.
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    Dynamic expression of H-type vessels coupled with bone repair effect in bone induced membrane for massive bone defects
    Shen Zhen, Huang Ziyue, He Zhijuan, Wang Yiting, Chen Qigang, Geng Chunmei, Huang Yajing, Wu Zugui
    2025, 29 (28):  5950-5956.  doi: 10.12307/2025.479
    Abstract ( 194 )   PDF (2089KB) ( 58 )   Save
    BACKGROUND: Slow bone repair and poor bone formation quality are still problems during masquelet technique in the treatment of large segment bone defects. H-type vessels can induce osteogenesis, enhance the local angiogenesis and osteogenesis coupling, and promote bone repair. However, there are few reports on the role of H-type blood vessels in the bone induced membrane. 
    OBJECTIVE: To construct a large segment bone defect model of SD rat tibia, observe the expression characteristics of H-type blood vessels in the bone induced membrane, then to identify the expression peak point of H-type blood vessels in the bone induced membrane and determine the optimal period of bone grafting.
    METHODS: Sixty SD rats were randomly divided into a control group (n=30) and a model group (n=30) by random number table method. The two groups were further divided into three subgroups at 4, 6, and 8 weeks after bone cement implantation, with 10 rats in each group. A 4 mm bone defect model of the right tibia was constructed in both the control and the model groups. Polymethyl methacrylate bone cement was implanted in the model group to induce bone biomembrane formation, while bone cement was not implanted in the control group. At 4, 6, and 8 weeks after bone cement implantation, 6 rats were randomly selected at each time point. The bone induction membrane tissue was cut from the model group, and the non-bone soft tissue of the corresponding part was cut from the control group. The dynamic expressions of H-type blood vessels in the bone induced membrane were identified by immunofluorescence. The morphological changes of the bone induced membrane were observed by hematoxylin-eosin staining. The formation of blood vessels in the bone induced membrane was observed by angiography. The expression levels of osteoblast-specific transcription factor in the bone induced membrane were detected by immunohistochemistry. Four rats remained at each time point. In the model group, the bone induced membrane was cut open and the bone cement was removed and autologous coccyx was implanted. In the control group, autologous coccyx was implanted in the bone defect area. Micro-CT evaluation of the tibial defect was performed 8 weeks after bone grafting. 
    RESULTS AND CONCLUSION: (1) Immunofluorescence staining showed that the expression of H-type vessels in the model group was most obvious 6 weeks after bone cement implantation, and the expression of H-type vessels in the model group at each time point after bone cement implantation was higher than that in the control group (P < 0.05). (2) Hematoxylin-eosin staining and angiography showed that the number and volume of new blood vessels at each time point after bone cement implantation in the model group were greater than those in the control group (P < 0.05). The order of the number and volume of new blood vessels in the model group was: 8 weeks after bone cement implantation > 6 weeks after bone cement implantation > 4 weeks after bone cement implantation. (3) Immunohistochemical staining showed that the positive expression of osteoblast-specific transcription factors at each time point after bone cement implantation in the model group was higher than that in the control group (P < 0.05), and the positive expression of osteoblast-specific transcription factors in the model group was most obvious 6 weeks after bone cement implantation. (4) Micro-CT detection showed that the bone repair effect of the three subgroups in the model group was significantly better than that of the corresponding subgroups in the control group, and the bone repair effect of the subgroup in the model group 6 weeks after bone cement implantation was better than that of the subgroups 4 and 8 weeks after bone cement implantation. The results indicate that H-type blood vessels are dynamically expressed in the bone induced membrane and reached a peak 6 weeks after bone cement implantation. Good bone repair effects can be obtained by the bone induced membrane bone grafting 6 weeks after bone cement implantation. 
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    Techniques and performance of biominerals for fabricating bone tissue engineering scaffolds
    Gang Fangli, Dang Zhongxiu, Li Ruiyun, Li Xiao, Sun Xiaoyang
    2025, 29 (28):  5957-5967.  doi: 10.12307/2025.485
    Abstract ( 214 )   PDF (4409KB) ( 79 )   Save
    BACKGROUND: In recent years, methods for incorporating biominerals into bone tissue engineering scaffolds have been extensively studied, including solvent casting, freeze-drying, and 3D printing. However, the diverse types and complex compositions of biominerals lead to varying impacts on scaffold performance and differing requirements for fabrication processes, necessitating systematic research on their applicability.
    OBJECTIVE: To explore biomineral grinding and screening processes, and evaluate their solution rheological properties, hydrophilicity, mechanical properties, and biocompatibility when prepared as composite materials with polymer materials. 
    METHODS: Five representative biominerals were selected, including turtle shell, eggshell, cuttlebone, deer antler, and pearl. These were ground into powders and screened, then mixed with polycaprolactone in specific proportions to prepare composite materials. The feasibility of applying biominerals in bone tissue engineering was explored by testing the elemental composition and particle size distribution of the powder, as well as the solution rheological properties, hydrophilicity, mechanical properties, and biocompatibility of the composite material.
    RESULTS AND CONCLUSION: (1) Most biomineral powders followed the rule that the longer the grinding time, the smaller the particle size. The desired particle size range could be obtained through methods such as sieving. Elemental mapping and Fourier Transform Infrared spectroscopy analyses indicated that the main inorganic mineral components of these five biominerals were calcium carbonate and calcium phosphate, containing the elements C, O, P, and Ca. (2) The method of dissolving polycaprolactone in 1,4-dioxane and adding biomineral powders to prepare scaffolds did not significantly alter the composite material composition and did not reduce biocompatibility. The addition of biomineral powders improved the hydrophilicity and 3D printability of polycaprolactone materials but decreased their mechanical properties. (3) These findings suggest that when applying biomineral powders to bone tissue engineering scaffolds, the proportion of powder added should be carefully chosen to balance hydrophilicity, printability, and mechanical properties. 
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    Syringin-chitosan hydrogel suppresses intervertebral disc degeneration
    Xi Haixiang, Duan Jie, Xu Ping, Fei Xi, Li Xiaoping, Cao Lei, Tang Guangping, Zhang Lei
    2025, 29 (28):  5968-5976.  doi: 10.12307/2025.484
    Abstract ( 171 )   PDF (1630KB) ( 136 )   Save
    BACKGROUND: Studies have shown that intradiscal injection of syringin solution can improve the structure and function of the intervertebral disc, prevent and slow down the process of intervertebral disc degeneration in rats. However, the biological half-life of syringin is short and it is difficult for it to continue to play a role in the intervertebral disc. Its bioavailability needs to be further improved.
    OBJECTIVE: To observe the effect of syringin-chitosan hydrogel on intervertebral disc degeneration in rats and the mechanism of syringin in the treatment of intervertebral disc degeneration. 
    METHODS: (1) Cell experiment: Passages 2-5 rat nucleus pulposus cells were divided into four groups for treatment. The normal control group did not undergo any treatment. The degeneration group was added with interleukin-1β (to establish the intervertebral disc degeneration cell model). The drug group was added with interleukin-1β and syringing. The inhibitor group was added with interleukin-1β, syringing, and phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. After 24 hours of treatment, apoptosis, extracellular matrix, oxidative stress, and apoptosis-related proteins and PI3K/protein kinase B (AKT) signaling pathway proteins were detected respectively. (2) Animal experiment: Syringin-chitosan hydrogels were prepared, and the micromorphology and slow-release properties of the hydrogels were tested. Thirty SD rats were randomly divided into model control group, model intervention group, hydrogel group, syringin solution group, and syringin hydrogel group, with 6 rats in each group. The intervertebral disc degeneration model was established by the acupuncture method. Immediately after model establishment, the rats in model intervention group, hydrogel group, syringin solution group, and syringin hydrogel group were injected with PBS, chitosan hydrogel, syringin solution, and syringin-chitosan hydrogel, respectively. The samples were taken 8 weeks after modeling for histological detection.
    RESULTS AND CONCLUSION: (1) Cell experiment: Compared with the normal control group, apoptosis rate, reactive oxygen species level, and expression of BAX, cleaved caspase-9, cleaved caspase-3, and matrix metalloproteinase 13 protein were increased in the nucleus pulpocytes in the degeneration group (P < 0.05), and the expression levels of p-PI3K, p-AKT, BCL-2, and type II collagen were decreased (P < 0.05). Superoxide dismutase activity decreased (P < 0.05). Compared with the degeneration group, apoptotic rate, reactive oxygen species level, and expression of BAX, cleaved caspase-9, cleaved caspase-3, and matrix metalloproteinase 13 protein were decreased in the syringin solution and syringin solution groups (P < 0.05), and expression levels of p-PI3K, p-AKT, BCL-2, and type II collagen were increased (P < 0.05). Superoxide dismutase activity increased (P < 0.05). LY294002 could partially inhibit the effect of syringin. (2) Animal experiment: Syringin-chitosan hydrogel had a loose porous structure and good slow-release performance. Hematoxylin-eosin and safranin O-fast green staining showed that compared with the model control group and model intervention group, chitosan hydrogel, syringin solution and syringing-chitosan hydrogel could improve the intervertebral disc degeneration in different degrees, and the therapeutic effect of syringing-chitosan hydrogel was better than that of hydrogel and drug solution alone. (3) These findings indicate that syringin can regulate apoptosis of nucleus pulposus cells and extracellular matrix degradation induced by oxidative stress by activating PI3K/AKT signaling pathway, thus delaying disc degeneration. Compared with syringin injection alone, syringin loading in chitosan hydrogel can further delay the progression of intervertebral disc degeneration in rats. 
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    Bone cement injection during percutaneous curved vertebroplasty in treatment of osteoporotic vertebral compression fractures in the upper 1/3 of the vertebral body
    Li Tangbo, Zhang Nan, Hao Guobing, Liu Kun, Qiao Lin, Zhu Zexing, Song Diyu
    2025, 29 (28):  5977-5984.  doi: 10.12307/2025.465
    Abstract ( 156 )   PDF (2439KB) ( 66 )   Save
    BACKGROUND: Percutaneous curved vertebroplasty has the advantages of minimal trauma and bone cement dispersion, but whether it is safe and effective for the treatment of compression fractures in the upper 1/3 of the vertebral body needs further study.
    OBJECTIVE: To investigate the clinical efficacy of percutaneous curved vertebroplasty in the treatment of the upper 1/3 compression fractures of the osteoporotic vertebrae.
    METHODS: Medical records of 66 patients with osteoporotic thoracolumbar upper 1/3 compression fracture admitted to Department of Orthopedics of PLA Rocket Force Characteristic Medical Center from January 2020 to June 2023 were retrospectively analyzed. Among them, 32 cases were treated with percutaneous curved vertebroplasty (observation group) and 34 cases were treated with “noncoplanar bipedicular puncture” percutaneous vertebroplasty (control group). Pain visual analog scale score, Oswestry Disability Index, anterior edge height of injured vertebra, and Cobb angle of injured vertebra were compared and analyzed between the two groups before surgery, the first day after surgery, and the last follow-up. The operative time, bone cement leakage rate, bone cement injection volume, and bone cement dispersion score of the two groups were statistically analyzed. 
    RESULTS AND CONCLUSION: (1) The operations were successfully completed in both groups of patients, and no complications such as bone cement allergy, bone cement embolism, nerve damage, or epidural hematoma occurred. (2) Pain visual analog scale score, Oswestry disability index, anterior edge height, and Cobb angle of injured vertebra of the two groups at the first day after surgery and the last follow-up were all better than those before surgery, with statistically significant difference (P < 0.05), but there was no statistical significance between the two groups (P > 0.05). The Oswestry disability index of the two groups at the last follow-up was better than that on the first day after surgery (P < 0.05). (3) The operation time and bone cement leakage rate of the observation group were lower than those of the control group, and the differences were statistically significant (P < 0.05). (4) There were no significant differences in bone cement injection volume and bone cement dispersion score between the two groups (P > 0.05). (5) The results show that percutaneous curved vertebroplasty in the treatment of osteoporotic vertebrae compression fractures in the upper 1/3 of the vertebral body can effectively relieve pain, maintain vertebral height, and reduce operative time and bone cement leakage rate. 
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    Methods and effects on endotoxin removal in allogeneic bone
    Hou Licun, Hu Kai, Shao Yiran
    2025, 29 (28):  5985-5993.  doi: 10.12307/2025.471
    Abstract ( 207 )   PDF (2299KB) ( 55 )   Save
    BACKGROUND: Natural biomaterials such as allogeneic materials are highly susceptible to bacterial contamination during the production process. Among them, bacterial endotoxin released by Gram-negative bacteria can cause human fever, coagulation, shock, and even death. There is no relevant research on the method of endotoxin removed from allogeneic materials while maintaining their natural structure and biological activity. 
    OBJECTIVE: To explore the method and effect of endotoxin removed from allogeneic materials and other natural biological materials and to control the residual H2O2.
    METHODS: The endotoxin was removed from allogeneic bone materials by H2O2/ultrasound. The influence of ultrasound and the concentration of H2O2 on the endotoxin removal process was explored. The concentration of H2O2 was set as 1%, 2%, 3%, 4%, and 5% by mass. The power of ultrasound was set as 80, 120, 140, 160, and 200 W. The duration of ultrasound was 20, 30, 40, 50, and 60 minutes. The temperature was 30, 35, 40, 45, and 50 ℃. The optimal combination of conditions for treating allogeneic bone materials was selected by endotoxin content detection for subsequent experiments. The microstructure, H2O2 residue, and cytotoxicity of allogeneic bone materials after endotoxin removal were detected, and the effects of different concentrations of H2O2 residue on the survival rate of L929 mouse fibroblasts were explored. 
    RESULTS AND CONCLUSION: (1) According to the results of the endotoxin removal process, when the concentration of H2O2 was 4%, the power of ultrasound was 200 W, with the duration of ultrasound of 50 minutes, and the temperature 50 ℃, it would effectively remove endotoxin from allogeneic bone materials. The optimal combination was selected to remove endotoxins from allogeneic bone materials. (2) After endotoxin removal, the residual H2O2 content of allogeneic bone materials was less than 47.551 mg/kg after being placed in a 60 ℃ water bath and changing the solution 6 times, which had no effect on the viability of L929 mouse fibroblasts. (3) Optical microscopy and scanning electron microscopy observations exhibited that the use of H2O2 solution in conjunction with ultrasonic treatment had no effect on the structure of allogeneic bone materials. (4) The results indicate that the H2O2 solution in conjunction with ultrasonic treatment has the characteristics of efficient and rapid removal of endotoxins, which can ensure the safety of allogeneic bone materials.
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    Effect of silicate bioactive glass fiber on properties of calcium phosphate bone cement
    Lu Yuzheng, Xiong Yingjie, Shan Yanbo, Ye Jianting, Wu Yanbin, Song Jipeng, Zhang Yao, Lin Wancheng, Weng Qirui, Cheng Xuan, Meng Haoye, Xu Wenjing, Peng Jiang, Ding Lixiang
    2025, 29 (28):  5994-6002.  doi: 10.12307/2025.473
    Abstract ( 232 )   PDF (2345KB) ( 104 )   Save
    BACKGROUND: The development of calcium phosphate bone cement is limited due to its poor mechanical properties and weak osteogenic ability. Silicate bioactive glass is highly favored due to its excellent biological activity and osteogenic ability. Simultaneously, fiber structures can enhance the mechanical strength of materials. 
    OBJECTIVE: To investigate the mechanical properties, biocompatibility, and osteogenic effect of silicate bioactive glass fiber composite calcium phosphate bone cement. 
    METHODS: Different mass percentages (0%, 10%, and 20%) of silicate bioactive glass fiber were added to the solid phase of calcium phosphate bone cement, mixed with the liquid phase and cured for 48 hours to obtain silicate bioactive glass fiber composite calcium phosphate bone cement. The mechanical properties, setting time, and ion precipitation of the cement were characterized. The three groups of bone cement extracts were co-cultured with MC3T3-E1 cells. The cell compatibility of the materials was evaluated by CCK-8 assay, live/dead staining, and phalloidin staining. After osteogenic induction, the osteogenic induction ability of the materials was evaluated by alkaline phosphatase staining, alizarin red staining, RUNX2 immunofluorescence staining, and RT-PCR.
    RESULTS AND CONCLUSION: (1) With the increase of silicate bioactive glass fiber content, the compressive strength and flexural strength of bone cement increased, and the setting time was prolonged. When bone cement was immersed in simulated body fluid, the precipitation of silicon ions, calcium ions, and phosphorus ions could be detected. Moreover, with the increase of silicate bioactive glass fiber content, the mass concentration of silicon ions and phosphorus ions released by bone cement increased, and the mass concentration of calcium ions decreased. (2) Live/dead staining and phalloidin staining results exhibited that silicate bioactive glass fiber composite calcium phosphate bone cement had no toxic effect on MC3T3-E1 cells. CCK-8 assay results showed that silicate bioactive glass fiber composite calcium phosphate bone cement could promote the proliferation of MC3T3-E1 cells. (3) With the increase of silicate bioactive glass fiber content in bone cement, the alkaline phosphatase activity and extracellular calcium deposition of MC3T3-E1 cells increased, the expression of RUNX2 protein increased, and the expression of alkaline phosphatase, osteocalcin, osteopontin, and RUNX2 mRNA expression increased. (4) The results indicate that silicate bioactive glass fibers can enhance the mechanical properties and osteogenic induction ability of calcium phosphate bone cement, among which 20% silicate bioactive glass fibers have a more obvious effect.
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    Design of customized Gyroid condylar prosthesis and finite element analysis of articular disc
    Jiang Tingting, Liu Danyu, Jiang Zhixiu, Ji Yuchen, Cao Yilin, Su Yucheng, Wang Xinyu
    2025, 29 (28):  6003-6011.  doi: 10.12307/2025.460
    Abstract ( 193 )   PDF (2471KB) ( 79 )   Save
    BACKGROUND: Condylar prosthesis replacement, as one of the surgical methods for the treatment of temporomandibular joint diseases, not only needs to restore the morphology and function, but also needs to ensure long-term stable application.
    OBJECTIVE: To design finite element analysis of a customized Gyroid condylar prosthesis. 
    METHODS: Gyroid structure specimens with different wall thicknesses (250, 350, 450, 550, 650, and 750 µm) were designed by software. Finite element simulation compression experiments were carried out to test the elastic modulus of the specimens. The Gyroid structure wall thickness range that matches the elastic modulus of mandibular cancellous bone and whose pore size meets the osteogenesis conditions was screened out. This range was subdivided and Gyroid structure specimens were made using 3D printing technology. Mechanical compression experiments were carried out on a universal testing machine. The Gyroid structure wall thickness that meets the mechanical properties of mandibular bone, has an easier osteogenesis and a smaller strength was screened out by elastic modulus and compressive strength, and subsequent experiments were carried out. A three-dimensional model of a customized Gyroid condylar prosthesis was designed, and the finite element analysis of the blade jaw position and cusp interdigitation position of the model under natural occlusion was simulated.
    RESULTS AND CONCLUSION: (1) Finite element analysis results showed that with the increase of wall thickness, the elastic modulus of Gyroid structure specimens increased. The elastic modulus of Gyroid structure specimens with wall thickness of 350, 450, 550, 650, and 750 µm matched the elastic modulus of mandibular cancellous bone. Since the subsequent experiments needed to be subdivided into groups and the pore size of the 550, 650, and 750 µm wall thickness group (pore size 800-1 000 μm) was within the osteogenesis range. Gyroid structure specimens with wall thickness of 550, 600, 650, 700, and 750 µm were selected for mechanical compression experiments on a universal testing machine. (2) The results of mechanical compression experiments showed that with the increase of wall thickness, the elastic modulus and compressive strength of Gyroid structure specimens increased. The elastic modulus of Gyroid structure specimens with wall thickness of 550, 600, and 650 µm was within the elastic modulus of the mandibular cancellous bone. Finally, the wall thickness of 650 μm and the pore size of 900 μm were selected to construct the three-dimensional model of the mandibular customized Gyroid condylar prosthesis. (3) The results of finite element analysis of three-dimensional model of the mandibular customized Gyroid condylar prosthesis showed that the stress of the articular disc in the edge-to-edge occlusion was mainly concentrated on the lower surface of the anterior middle band, and the stress of the articular disc in the interposition of tooth tips was mainly concentrated on the lateral surface of the lower surface. The maximum displacement and the maximum equivalent stress of the left and right articular discs in the edge-to-edge occlusion and the interposition of tooth tips were similar. The maximum displacement was 0.031, 0.030, 0.028, and 0.018 mm, and the maximum equivalent stress was 2.87, 2.30, 2.73, and 1.71 MPa, respectively. (4) The results showed that the Gyroid structure with a wall thickness of 650 μm was consistent with the mechanical properties of the mandible, which reduced the strength of the titanium alloy and reduced the damage of the articular disc caused by the customized Gyroid condylar prosthesis. 
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    Finite element analysis on miniscrews and hooks with different locations assisted clear aligners in maxillary molar distalization
    Ye Panpan, Xu Changxi, Li Hui, Zhang Yang, Xu Xiaolin, Wang Hongning
    2025, 29 (28):  6012-6019.  doi: 10.12307/2025.474
    Abstract ( 177 )   PDF (2168KB) ( 89 )   Save
    BACKGROUND: The utilization of miniscrews for assisting in molar distalization with clear aligners is a commonly adopted clinical approach. However, treatment outcomes may be influenced by the implantation position of miniscrew and the hooks in various tooth location.
    OBJECTIVE: To analyze the biomechanical effects of hooks at different tooth positions and the assistance of buccal and palatal miniscrews in distalizing molars with clear aligners by using the finite element method.
    METHODS: By integrating volunteer cone beam CT and Itero intraoral scan data, high-precision finite element models were constructed to simulate the combined use of miniscrews and hooks to assist in the distalization of the maxillary first and second molars with clear aligners, aiming for a designed distalization magnitude of 0.2 mm. Four conditions were established based on the placement of buccal or palatal miniscrews, as well as the located of hooks at the canine or first premolar. The buccal anchorage screw was used in combination with hooks on the buccal side of the canine; the buccal anchorage screw was used in combination with hooks on the buccal side of the first premolar; the palatal anchorage screw was used in combination with hooks on the lingual side of the canine, and the palatal anchorage screw was used in combination with hooks on the lingual side of the first premolar. Analysis using ANSYS software was conducted to evaluate the three-dimensional displacement trends of maxillary teeth and the maximum equivalent stress on the periodontal ligament under each condition. 
    RESULTS AND CONCLUSION: (1) Regardless of whether hooks were placed on canines or first premolars, palatal miniscrews had been shown to enhance the distal movement of maxillary molars and reduce the mesial movement of premolars as well as the labial tipping tendency of anterior teeth, compared to buccal miniscrews. The maximum equivalent stress in the periodontal ligament of molars was increased, while that of anterior teeth was decreased. (2) Regardless of whether the miniscrews were located on the buccal or palatal side, compared with hooks at the first premolar, when hooks were done at the canine, the labial inclination trend of the anterior teeth was reduced, the distal movement of the molars was reduced, the mesial movement of the premolars was increased, and the maximum equivalent stress of the molar and the periodontal membrane of the anterior teeth was reduced. (3) Regardless of whether miniscrews were located on the buccal or palatal side, and the hooks were located on the canine or the first premolar, the molar could not achieve overall movement. (4) The results show that clear aligner combined with palatal miniscrews and hooks at the first premolar are more conducive to improving the efficiency of maxillary molar distalization, but attention should be paid to protecting the anterior tooth miniscrews and molar torque control; clear aligner combined with palatal miniscrews and hooks at the canine is more conducive to reducing the labial tipping tendency of anterior teeth, but the efficiency of molar distalization will be relatively reduced.
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    Finite element analysis of stress distribution on mandibular All-on-4 implant fixed denture with different occlusion
    Wu Zhengmin, Li Changxu, Cui Yanwei, Chen Su
    2025, 29 (28):  6020-6029.  doi: 10.12307/2025.480
    Abstract ( 219 )   PDF (2457KB) ( 68 )   Save
    BACKGROUND: The long-term effect of All-on-4 implant fixed denture is closely related to biomechanics. Its occlusion design affects the stress distribution of every part of the restoration. However, there is limited and inconclusive biomechanical research on All-on-4 implant fixed denture both domestically and internationally so far. 
    OBJECTIVE: To analyze the effect of different occlusal contacts on the stress distribution of mandibular All-on-4 implant fixed denture. 
    METHODS: A model of mandibular All-on-4 implant fixed denture was established. By changing the loading force, direction, and position, 10 loading conditions were set up to simulate centric occlusion, laterotrusive occlusion, and protrusive occlusion. The stress distribution and maximum stress values of every part of the model in different loading conditions were analyzed and compared among each group of models by loading different tooth positions to simulate different occlusal contact types.
    RESULTS AND CONCLUSION: (1) The stress distribution cloud diagrams of each group of models were basically similar. The stress of the implant was mainly concentrated at the implant neck. The stress of the surrounding bone tissue was mainly concentrated around the implant neck, and the stress of the cortical bone was significantly higher than that of the cancellous bone. The stress of the abutment was mainly concentrated at the connection between the abutment and the implant and the abutment and the upper restoration. The stress of the titanium bracket in the upper restoration was mainly concentrated at the connection between the abutment and the titanium bracket, and the stress of the resin surface in the upper restoration was mainly concentrated on each loading point. (2) In simulating centric occlusion, the maximum stress value of the implant significantly increased when the cantilever was not loaded. It indicates that the mandibular All-on-4 implant fixed denture can have occlusal contact in the distal cantilever during centric occlusion. (3) In simulating laterotrusive occlusion, the maximum stress values of every part of the model significantly increased when simulating canine-guided occlusion. The maximum stress value of the simulated laterotrusive balanced occlusion was slightly lower than that of the simulated group functional occlusion. It indicates that group functional occlusion can be selected in the permanent prosthesis after osseointegration and laterotrusive balanced occlusion can be selected in the provisional restoration of mandibular All-on-4 implant fixed denture. (4) In simulating protrusive occlusion, the maximum stress values of every part of the model significantly increase when only the front tooth is loaded. In simulating protrusive balanced occlusion, the maximum Von-Mises stress value is relatively small. It indicates that the protrusive occlusion of mandibular All-on-4 implant fixed denture can choose protrusive balanced occlusion.
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    Effect of clear and fixed aligners on smooth surface of teeth analyzed by Universal Visual Scoring System
    Lu Lin, Li Yanan, Zhang Fan, Dou Chenlei, Li Qiutong, Shan Lihua
    2025, 29 (28):  6030-6036.  doi: 10.12307/2025.461
    Abstract ( 178 )   PDF (997KB) ( 67 )   Save
    BACKGROUND: Leukoplakia is a common adverse reaction to traditional orthodontic treatment. There are still some controversies about the difference between light-transmitting clear and fixed aligners in the periodontal health status, incidence of leukoplakia, saliva and related bacteria in patients undergoing orthodontic treatment.
    OBJECTIVE: To compare the effects of clear and fixed aligners on the smooth surface of orthodontic teeth using Universal Visual Scoring System. 
    METHODS: A total of 80 patients admitted to Department of Orthodontics, Second Hospital of Hebei Medical University from January 2018 to December 2022 were selected and randomly divided into a control group (n=40) and an observation group (n=40) using a random number table method. The control group received orthodontic treatment with fixed aligners, and the observation group received orthodontic treatment with clear aligners. Before treatment and after 6, 12, and 24 months of treatment, the labial or buccal sides of teeth 13, 33, 16, and 36 were selected for each patient as the research subjects, and the visual scoring system was used to evaluate the white spot lesions. 
    RESULTS AND CONCLUSION: (1) Before treatment and after 6, 12, and 24 months of treatment, there was no significant difference in the color of tooth white spots and the severity of caries between the two groups of patients (P > 0.05). (2) For tooth 13, after 12 months of treatment, the color grade and caries severity of white spots were both higher than before treatment (P < 0.05). For tooth 33, the color grade and caries severity after 12 months of treatment were both higher than before treatment (P < 0.05). The severity of caries after 12 months of treatment was higher than that after 6 months of treatment (P < 0.05). For tooth 16, the color grade of white spots and the severity of caries after 12 months of treatment were both higher than those after 6 months of treatment (P < 0.05). (3) Multi-level ordered multi-classification Logistic regression model analysis showed that the color and severity of white spots on different teeth had little correlation with the type of appliance and were greatly affected by the correction time factor. Among them, the color change and severity of the initial white spots on teeth 33 and 13 were statistically significant at 12 and 24 months of treatment. (4) It is not possible to conclude that there is a difference in the effect of fixed and clear aligners on the white spot lesions of smooth surfaces of the teeth, but an increase in the risk of dental caries with the increase in the duration of treatment can be detected.
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    A method for characterizing the crosslinking reaction process of sodium hyaluronate based on compressive stress
    Zhang Jianchao, Xiao Li, Zhang Kun
    2025, 29 (28):  6037-6045.  doi: 10.12307/2025.475
    Abstract ( 182 )   PDF (1542KB) ( 82 )   Save
    BACKGROUND: Currently, the crosslinking process of gels can be characterized by the degree of crosslinking measured by nuclear magnetic resonance and other methods, or by the change of viscoelastic behavior monitored by the rheometer during the crosslinking solidification process. However, these methods are complicated to operate and will destroy the sample, so it is urgent to establish a simple method to monitor the crosslinking reaction process without special sample preparation and without sample damage. 
    OBJECTIVE: To establish a method for characterizing the crosslinking reaction process of sodium hyaluronate. 
    METHODS: 1,4-Butanediol diglycidyl ether was used as the cross-linking agent, and four factors were selected to prepare sodium hyaluronate gels, including different cross-linking degrees (1%, 2%, 3%, and 4%), different molecular weights of sodium hyaluronate (400, 700, 1 500, and 3 000 kD), different concentrations of sodium hydroxide solution (1%, 2%, and 3%), and different reaction temperatures (4, 25, 37, and 50 ℃). The compression stress of the crosslinked gel was measured by an electronic universal tensile testing machine when the cross-linked gel was pressed down and deformed for 1 mm. The influence of crosslinking parameters on the reaction process and adequacy sufficiency of the crosslinking reaction were characterized according to the compressive stress. 
    RESULTS AND CONCLUSION: (1) With the extension of reaction time, the hardness of gel increased, and the compressive stress gradually increased. After reaching a certain value, the cross-linked macromolecular structure of sodium hyaluronate degraded under the action of strong alkali, and the gel hardness reduced while the compressive stress decreased. Therefore, the hardness of the gel could be characterized according to the compressive stress. The process of crosslinking reaction was characterized by the curve drawn by compressive stress and crosslinking time. According to compressive stress, the crosslinking reaction temperatures had significantly influenced the crosslinking reaction time and the gel hardness, whereas other factors such as crosslinking degree, alkali concentration, and molecular weight had negligible effects on the reaction time but exerted a substantial impact on the gel hardness. (2) According to CORREL, with the change of crosslinking time, the change trend of compressive stress was consistent with that of elastic modulus and dynamic viscosity, which could be used to characterize the crosslinking process of sodium hyaluronate gel. (3) Based on the compression force of cross-linked gel, not only the process of crosslinking reaction can be characterized, but also the gel hardness can be preliminarily determined. This method can be used for real-time and in-situ detection and has the advantages of simple operation and no damage to the sample, providing a solution and new ideas for monitoring the crosslinking reaction process of sodium hyaluronate or other substances.
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    Changes in properties of treated allogeneic tendons after multiple freeze-thaw cycles
    Hu Kai, Guo Yongqin, Shao Yiran, Wang Jingjing
    2025, 29 (28):  6046-6051.  doi: 10.12307/2025.487
    Abstract ( 87 )   PDF (1315KB) ( 72 )   Save
    BACKGROUND: Allogeneic tendons are often used in clinical treatment of tendon and ligament injuries, which need to be treated before clinical application. At present, allogeneic tendons will face multiple freeze-thaw cycles after cryopreservation, but there is no relevant research on the changes in the properties of the treated allogeneic tendon after several freeze-thaw cycles.
    OBJECTIVE: To explore the changes in mechanical properties and composition of allogeneic tendon after multiple freeze-thaw cycles.
    METHODS: The treated allogeneic tendon was frozen and thawed 3, 6, and 10 times at -40 ℃ (or -80 ℃), respectively. The mechanical test, DNA content, glycosaminoglycan sulfate, hydroxyproline content and total protein content of the allogeneic tendon after freezing and thawing were detected. 
    RESULTS AND CONCLUSION: (1) There was no significant difference in the maximum load, maximum load elongation, tensile strength and elastic modulus between groups after freezing-thawing cycles for 3, 6, and 10 times at -40 ℃ (P > 0.05). There was no significant difference in the maximum load and maximum load elongation between the groups after freezing-thawing cycles for 3, 6, and 10 times at -80 ℃ (P > 0.05). The tensile strength of the group with 3 cycles of freezing and thawing was higher than that of the groups with 6 and 10 cycles of freezing and thawing (P < 0.05). The elastic modulus of the group with 3 cycles of freezing and thawing was higher than that of the group with 10 cycles of freezing and thawing (P < 0.05). (2) The freezing and thawing times did not affect the contents of DNA, hydroxyproline, total protein, and sulfated glycosaminoglycan in allogeneic tendon when stored at -40 ℃ (or -80 ℃). (3) These findings suggest that in -40℃ storage, the performance of the allogeneic tendon should not be affected by taking out and putting back the tendon less than 10 times, while in -80 ℃ storage, the allogeneic tendon should be taken out and put back less than 6 times.
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    MXene nanoparticles Ti3C2Tx and photothermal effect promote wound healing in diabetic mice
    Li Meiyun, Liu Sen, Chen Kaiyuan, Shi Ling, Song Meichen, Cao Jiahong, Wu Yan, Yu Jing
    2025, 29 (28):  6052-6060.  doi: 10.12307/2025.489
    Abstract ( 242 )   PDF (2339KB) ( 137 )   Save
    BACKGROUND: MXene nanoparticles, due to their unique hydrophilicity, biocompatibility, and antibacterial properties, are widely used in wound, tumor, nerve repair, and cardiovascular treatments. However, it is still unclear what effect MXene nanoparticles have on diabetic wound healing.
    OBJECTIVE: To investigate the in vitro antioxidant, anti-inflammatory and photothermal antibacterial properties of MXene nanoparticles Ti3C2Tx as well as their effect on wound repair in diabetic mice.
    METHODS: (1) In vitro experiments: The cytotoxicity of Ti3C2Tx nanoparticles on mouse fibroblasts (NIH-3T3) at various concentrations was evaluated using the methyl thiazolyl tetrazolium (MTT) assay. NIH-3T3 cells were exposed to H2O2, and the MTT assay was used to detect the protective effects of different mass concentrations of Ti3C2Tx on NIH-3T3 cells. NIH-3T3 cells were exposed to H2O2, and the effect of Ti3C2Tx (20 μg/mL) on the generation of reactive oxygen species in NIH-3T3 cells was analyzed under illumination (or no illumination) treatment. RAW264.7 macrophages were divided into three groups: control group, lipopolysaccharide group, and lipopolysaccharide+Ti3C2Tx group. Real-time quantitative PCR was used to detect the expression of specific genes (CD86, interleukin 6, CD206, arginase 1) in the cells. Escherichia coli (or Staphylococcus aureus) were divided into three groups: control group, Ti3C2Tx group, and Ti3C2Tx illumination group. The bacterial survival rate was calculated by plate colony counting method. (2) In vivo experiments: Streptozotocin was administered intraperitoneally to ICR mice to induce a diabetic condition. After successful modeling, a full-thickness skin defect wound was created on the back of the mice using a circular punch. The experiment was divided into three groups: control group (n=6), Ti3C2Tx group (n=6), and Ti3C2Tx illumination group (n=6). The wound healing was observed, and CD31 and CD206 immunohistochemical staining of wound tissue was performed on day 7 after intervention. Hematoxylin-eosin staining and Masson staining of wound tissue were performed on days 7 and 14 after intervention. Ti3C2Tx solution was injected subcutaneously into ICR mice. After illumination (or non-illumination) exposure, the toxic effects of Ti3C2Tx on mice were analyzed by blood biochemical detection. 
    RESULTS AND CONCLUSION: (1) In vitro experiments: Ti3C2Tx showed no cytotoxicity on NIH-3T3 cells at mass concentrations ranging from 5-160 μg/mL. It increased the survival rate of NIH-3T3 cells at a mass concentration of 20 μg/mL. Ti3C2Tx at 10-80 μg/mL significantly improved the survival rate of NIH-3T3 cells under H2O2 intervention. Ti3C2Tx significantly inhibited the generation of reactive oxygen species in NIH-3T3 cells under the intervention of H2O2, and illumination treatment further enhanced the effect of Ti3C2Tx on inhibiting the generation of reactive oxygen species. Ti3C2Tx effectively inhibited macrophage inflammation induced by lipopolysaccharide and promoted the transformation of cells into M2 macrophages with anti-inflammatory properties. Both Ti3C2Tx and Ti3C2Tx illumination significantly inhibited the growth of Escherichia coli and Staphylococcus aureus, and the inhibitory effect of Ti3C2Tx illumination was more significant. (2) In vivo experiments: Gross and histological analyses of the wound surface showed that both Ti3C2Tx and Ti3C2Tx illumination promoted wound healing in diabetic mice, and the promotion effect of Ti3C2Tx irradiation was more significant. Immunohistochemical staining results showed that both Ti3C2Tx and Ti3C2Tx illumination inhibited the inflammatory response in diabetic wounds and promoted angiogenesis, and the effect of Ti3C2Tx illumination was more significant. Blood biochemical test results showed that Ti3C2Tx and illumination had no obvious toxic effects on mice. (3) These results indicate that Ti3C2Tx nanoparticles efficiently promote the healing of skin wounds in a diabetic mouse model through antioxidation, anti-inflammation, and antibacterial actions via photothermal effects.
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    Functionalized self-assembled micelles enhance effect of tranexamic acid in treatment of cutaneous hyperpigmentation
    Qi Junlong, Liu Junyi, He Yuzhou, Qiang Wei, Zhang Shiying, Liu Qiao, Zhu Hongda
    2025, 29 (28):  6061-6069.  doi: 10.12307/2025.488
    Abstract ( 172 )   PDF (1991KB) ( 104 )   Save
    BACKGROUND: Topical administration of tranexamic acid can be used for anti-skin pigmentation, but its large polarity makes it difficult to break through the cuticle barrier and cell membrane when administered topically, and the subcutaneous accumulation concentration is not easy to reach the effective therapeutic concentration.
    OBJECTIVE: To design functionalized self-assembled micelles to enhance the anti-pigmentation effect of tranexamic acid. 
    METHODS: The plant polyphenol derivative epigallocatechin gallate palmitate and metformin were used as carrier materials. The self-assembled micelles with synergistic anti-pigging activity and enhanced drug permeability were prepared by hydrogen bonding and electrostatic interaction. The nanoscale properties and stability of self-assembled drug-loaded micelles were tested, and their transdermal permeability was evaluated, and their biocompatibility and cellular effects were investigated.
    RESULTS AND CONCLUSION: (1) Functional self-assembled drug-carrying micelles with average particle size of (176.27±5.23) nm, polydispersity coefficient of 0.23±0.02, and the Zeta potential of (-25.67±0.98) mV had good stability. The mass concentrations of tranexamic acid and metformin in the self-assembled drug-carrying micelles were (20.03±0.12) and (6.67±0.08) mg/mL, respectively. The drug loadings of tranexamic acid and metformin in the self-assembled drug-carrying micelles were (19.97±0.12)% and (6.65±0.08)%, respectively. (2) In vitro transdermal results showed that the self-assembled drug-carrying micelles had higher penetration and intradermal retention per unit skin area, and could penetrate and diffuse to deeper parts of the skin. (3) MTT assay results demonstrated that undrug-loaded self-assembled micelles containing tranexamic acid 50-250 μg/mL had no toxic effects on mouse fibroblasts and mouse skin melanoma cells. The self-assembled drug-carrying micelles containing tranexamic acid 500 μg/mL had a slight toxic effect on mouse skin melanoma cells. The self-assembled drug-carrying micelles containing 50-500 μg/mL of tranexamic acid did not cause hemolysis and had good biological safety. (4) In vitro cell culture results showed that self-assembled drug-carrying micelles containing 500 μg/mL tranexamic acid could significantly inhibit the tyrosinase activity and melanin release of mouse skin melanoma cells, and the inhibitory effect was stronger than that of tranexamic acid solution or metformin solution alone. These results indicated that functionalized self-assembled micelles could synergize with tranexamic acid to inhibit tyrosinase activity, reduce melanin synthesis, and enhance the anti-skin pigmentation effect of tranexamic acid. 
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    Oriented electrostatically spun polycaprolactone/silk fibroin scaffold loaded with calcium titanate promotes peripheral nerve regeneration
    Liu Xiaojun, Shang Yuqing, Guan Wenchao, Xu Linlin, Li Guicai
    2025, 29 (28):  6070-6082.  doi: 10.12307/2025.481
    Abstract ( 210 )   PDF (4641KB) ( 147 )   Save
    BACKGROUND: Oriented polycaprolactone/silk fibroin blend electrospinning scaffolds can repair peripheral nerve damage and promote nerve regeneration, but the repair effect is limited, and it is necessary to further combine bioactive materials, growth factors, and other factors to prepare bionic neural scaffolds. Calcium titanate nanoparticles have the ability to promote adhesion between Schwann cells and have been widely used in the field of biomedical materials. 
    OBJECTIVE: To prepare polycaprolactone/silk fibroin-calcium titanate functionalized scaffolds by electrospinning technology, and to further explore the effect of the scaffold on Schwann cell viability and adhesion. 
    METHODS: Polycaprolactone/silk fibroin scaffolds were prepared by electrospinning technology. The optimal parameters were selected by adjusting the syringe flow rate, receiving device speed and spinning time during the preparation process for subsequent experiments. Under the optimal parameters, randomly oriented polycaprolactone/silk fibroin scaffolds (denoted as PCL/SF-R), oriented polycaprolactone/silk fibroin scaffolds (denoted as CTO-0), and oriented polycaprolactone/silk fibroin scaffolds containing 0.1, 0.5, and 1.0 mg/mL polydopamine modified calcium titanate (denoted as CTO-1, CTO-5, and CTO-10, respectively) were prepared by electrospinning technology. The physical properties of the five groups of scaffolds were characterized. The extracts of the five groups of scaffolds were co-cultured with rat fibroblast cell line (L929). Cell proliferation was detected by MTT assay. Rat Schwann cell line (RSC96) was inoculated on the five groups of scaffolds. Cell viability, cytoskeleton staining, and cytoskeleton and cell adhesion related genes were detected.
    RESULTS AND CONCLUSION: (1) The optimal parameters for preparing electrospinning scaffolds were as follows: syringe flow rate 15 µL/min, receiving device speed 1 800 r/min, and spinning time 1 hour. (2) The PCL/SF-R group had the largest water contact angle and the smallest elastic modulus, while the CTO-0 group had the smallest water contact angle and the largest elastic modulus. The degradation rate of the scaffolds in the CTO-0 group was lower than that in the CTO-1 group, and the degradation rate of the scaffolds decreased with the increase of the mass concentration of calcium titanate in the oriented scaffolds. (3) The scaffolds in the five groups had no toxic effects on L929 cells and had good biocompatibility. CCK-8 assay results showed that CTO-10 could improve the viability of RSC96 cells. Cytoskeleton staining results showed that the aspect ratio and cell protrusion length of cells on the oriented scaffolds were higher than those on the randomly oriented scaffolds. qPCR test results showed that the mRNA expressions of YAP and Cntn2 in the CTO-5 and CTO-0 groups were higher than those in the PCL/SF-R group (P < 0.05). (4) The results indicate that the oriented polycaprolactone/silk fibroin-calcium titanate scaffold has good biocompatibility, mechanical properties, and hydrophilicity, which can enhance the viability and migration ability of Schwann cells and promote peripheral nerve regeneration.
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    Application of induced membrane technique for repairing critical-sized bone defects: advantages and future development
    Li Shuyuan, Yang Dawen, Zeng Zhanpeng, Cai Qunbin, Zhang Jingtao, Zhou Qishi
    2025, 29 (28):  6083-6093.  doi: 10.12307/2025.467
    Abstract ( 231 )   PDF (1075KB) ( 142 )   Save
    BACKGROUND: The induced membrane technique (Masquelet technique) is a novel two-stage surgical approach for the reconstruction of large bone defects, gaining increasing popularity in clinical applications. However, the precise mechanism underlying its bone defect repair is still not fully understood. 
    OBJECTIVE: To review the background, repair mechanism and advantages of the induced membrane technique, the characteristics of the induced membrane, membrane-bone graft communication, selection of animal models, types and morphology of bone cement, the effects of loaded antibiotics on the induced membrane, choice of fixation methods, and bone tissue engineering materials to provide new insights for the future treatment of critical-sized bone defects and the improvement of the induced membrane technique.
    METHODS: A literature search was conducted in PubMed, Web of Science, and CNKI databases, covering publications from 1986 to 2024. A total of 890 references were retrieved. Manual screening and analysis were performed based on inclusion criteria related to the fundamental research of induced membrane technique, excluding those with poor relevance to the topic and duplicates. The included literature comprised original experimental studies, reviews, meta-analyses and other relevant publications. Finally, 72 articles were included for summary and analysis.
    RESULTS AND CONCLUSION: (1) The mechanism underlying the bone defect repair using this technique remains unclear, but both the membrane and bone grafting are indispensable. (2) The induced membrane is a distinctively layered tissue rich in various bone-forming related cells, growth factors, and blood vessels, with its vascularization and secretion of growth factors dynamically changing over time. (3) In terms of animal model selection, sheep are more similar to humans in anatomical structure, weight-bearing patterns, and bone remodeling. However, rats are more suitable considering their lower feeding costs, easier handling, and shorter modeling period. (4) Polymethyl methacrylate is not the only material that can be used to induce a biomembrane, and there may be more suitable materials capable of inducing higher-quality biomembranes. The recommended dose of antibiotics (primarily vancomycin) is 1-4 g per 40 g polymethyl methacrylate. (5) For animal fixation, especially in rats, the use of steel plates is more widespread, providing a more reliable and reproducible fixation method. (6) In the future, there is potential for new materials to replace autogenous bone and enhance the bone repair capabilities of the Masquelet technique.
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    Application characteristics of thermosensitive hydrogels in bone tissue engineering
    Liu Yang, Yang Jilei, Wang Wenli, Cui Yingying, Sun Qihao, Li Yourui
    2025, 29 (28):  6094-6100.  doi: 10.12307/2025.468
    Abstract ( 260 )   PDF (850KB) ( 136 )   Save
    BACKGROUND: Thermoresponsive hydrogels are widely used in bone tissue engineering due to their structural similarity to extracellular matrix and their intelligent temperature sensitivity.
    OBJECTIVE: To explain the mechanism of temperature-responsive hydrogels producing sol-gel phase transitions, classify them based on their sources, and summarize the applications of various temperature-responsive hydrogels in bone tissue engineering.
    METHODS: The first author searched for relevant literature on CNKI and PubMed databases from 2000 to 2024, using search terms “hydrogel, thermosensitive hydrogel, bone repair, bone regeneration, bone tissue engineering” in Chinese and English. A total of 70 eligible articles were finally selected for review.
    RESULTS AND CONCLUSION: The temperature-sensitive mechanism of thermosensitive hydrogels can be divided into negative sensitive and positive sensitive according to different reactions. Its composition is mainly divided into natural polymer and synthetic polymer. Current research has found that in addition to the traditional way of using temperature-sensitive hydrogels as scaffold materials for bone tissue engineering, 3D printed scaffolds are also gradually emerging. In addition, thermosensitive hydrogels can also be used in 3D cell culture and drug slow release due to their own characteristics. At present, the development of thermosensitive hydrogels is not perfect enough. There are still problems such as the inability to accurately control the phase transition temperature, sustained release rate, low mechanical strength, and low biodegradability. Therefore, developing thermosensitive hydrogels with more stable properties is still a problem that we should solve at present. 
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    Application of Janus micro/nanoparticles in biomedicine
    Chen Senlin, Zhu Zhou, Wan Qianbing
    2025, 29 (28):  6101-6109.  doi: 10.12307/2025.476
    Abstract ( 357 )   PDF (1053KB) ( 188 )   Save
    BACKGROUND: Janus micro/nanoparticles are widely used in the field of tissue engineering, drug delivery, cancer therapy, bioimaging, and sensing due to their shape, structure, and functional anisotropy.
    OBJECTIVE: To elucidate the cutting-edge applications of Janus micro/nanoparticles in biomedicine.
    METHODS: Relevant literature published between 2010 and 2024 was retrieved from CNKI, WanFang Data, PubMed, and Web of Science databases. Searches were conducted using Chinese search terms “Janus nanoparticle, Janus particle, dual-faced particle, drug delivery, cancer therapy, bioimaging, biosensing, tissue engineering” and English search terms “Janus nanoparticle, Janus particle, drug delivery, cancer therapy, biosensing, bioimaging, tissue engineering.” A total of 69 articles were selected for review after screening, organizing, summarizing, and synthesizing.
    RESULTS AND CONCLUSION: Janus micro/nanoparticles can be classified into three major categories based on their basic material properties: organic, inorganic, and organic-inorganic composites. Synthetic strategies consist of shielding, self-assembly, phase separation, microfluidics, and nucleation and growth techniques. Janus micro/nanoparticles exhibit high-efficiency drug delivery through characteristics such as high drug loading, gated release, and autonomous motion. In addition to enhancing traditional cancer treatment modalities (radiation and chemotherapy), Janus micro/nanoparticles can also be applied to emerging cancer treatment methods such as cell immunotherapy, protein drugs, and ferroptosis. Janus micro/nanoparticles serve as contrast agents to enhance bioimaging modalities (CT, MRI, and ultrasound) for high-quality imaging, guiding diagnosis and treatment. Janus micro/nanoparticles are utilized in tissue engineering for delivering growth factors, enhancing mechanical properties of biomaterials, and exhibiting antibacterial effects. Researchers have successfully tailored Janus micro/nanoparticles with desired functionalities by combining different organic polymers and inorganic materials using various synthetic strategies, enabling applications in complex biomedical fields. Despite current advancements, reports on the application of Janus micro/nanoparticles in tissue regeneration, large-scale production, and human clinical trials are relatively limited. Therefore, further research efforts are needed in the development, synthetic strategies, clinical safety assessment, and translation of such materials.
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    Role of functional hydrogels in tissue repair after traumatic brain injury
    Zhang Tong, Wang Yan, Yang Chunjia, Yue Qingkun, Wu Qingtian
    2025, 29 (28):  6110-6117.  doi: 10.12307/2025.478
    Abstract ( 221 )   PDF (944KB) ( 166 )   Save
    BACKGROUND: At present, traditional drug delivery routes (oral or intravenous injection) in clinical practice face the problem of difficulty in penetrating the blood-brain barrier, and the clinical treatment of open severe traumatic brain injury is often lower than expected. Hydrogels are a class of extremely hydrophilic three-dimensional network structure gels, which swell rapidly in water and can be maintained in the swelling state. Hydrogels swell rapidly in water and can remain in this swollen state. At present, some experimental studies have applied injectable functional hydrogel injection into the injured site to achieve the purpose of repairing damaged brain tissue, but this treatment strategy has not been applied in clinic.
    OBJECTIVE: To analyze the role of functional hydrogels in tissue repair after traumatic brain injury, discuss the promotion of nerve tissue regeneration after traumatic brain injury through different action modes, so as to propose new ideas for clinical treatment and basic research of traumatic brain injury. 
    METHODS: English key words “hydrogels, functional hydrogel, composite hydrogels, traumatic brain injury, tissue repair, neural regeneration” and Chinese key words “functional hydrogels, traumatic brain injury, tissue repair, nerve regeneration” were used to search the relevant articles published from August 2000 to March 2024 in PubMed, Web of Science, CNKI, and WanFang databases. The inclusion and exclusion criteria were formulated, and 60 relevant articles were finally included after being screened by reading the title, abstract, and full text of articles.  
    RESULTS AND CONCLUSION: (1) The hydrogel based on molecular design can simulate the neural microstructure, promote regeneration and repair, and simulate the neurovascular unit to promote vascular regeneration. (2) Hydrogels based on the principle of combined drug therapy can deliver endogenous neuroregulatory factors, coating drugs to promote nerve regeneration. (3) Hydrogels based on stem cell recovery strategies can be used as molecular scaffolds to deliver cell therapy. (4) Future researchers need to further explore functional hydrogels related to nerve tissue repair to provide effective strategies for therapeutic function reconstruction in traumatic brain injury patients. 
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    Application of graphene oxide in field of oral implant restoration
    Shi Chunrong, He Jiaxu, Deng Lishan, Wang Hailan, Zhao Aimin, Yu Yiling, Geng Haixia, Song Weijun
    2025, 29 (28):  6118-6126.  doi: 10.12307/2025.482
    Abstract ( 230 )   PDF (1094KB) ( 173 )   Save
    BACKGROUND: Graphene oxide, with its excellent physical and chemical properties and biocompatibility, can promote the differentiation of osteoblasts and inhibit the proliferation of bacteria, which will hopefully improve the success rate of implant restoration. 
    OBJECTIVE: To summarize the research progress of graphene oxide in the field of dental implant restoration.
    METHODS: The related articles published by CNKI, WanFang Database, ScienceDirect, and PubMed from January 2000 to June 2024 were searched by computer. The keywords were “graphene oxide, dental implantation, biocompatibility, antibacterial mechanism, osteoblasts, mechanical properties, chemical properties” in Chinese and English. By reading the titles and abstracts, we preliminarily screened out the documents irrelevant to the topic of the article. According to the inclusion and exclusion criteria, 65 documents were finally included for analysis.
    RESULTS AND CONCLUSION: Graphene oxide can increase the innate immune protection response of the body through its own antibacterial and drug-loaded antibacterial abilities, thus inhibiting the occurrence and development of periimplant inflammation. Graphene oxide can promote the proliferation and differentiation of bone marrow mesenchymal stem cells, enhance the proliferation of osteoblasts and vascular endothelial cells, inhibit the proliferation of osteoclasts, increase the rate of bone bonding between implants and alveolar bones, and contribute to the formation and stability of bone around implants. Graphene oxide can promote the combination of implant and gingival tissue, and reduce the occurrence of inflammation. Graphene oxide has low toxicity, and its biological safety needs further study. Graphene oxide coating endows the surface of titanium implant with excellent physical and chemical properties, which can greatly reduce the occurrence of complications such as implant fracture and prolong the survival time of implant.
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    New ideas and opportunities for polyurethane materials in peripheral nerve repair
    Lan Xiaoqian, Feng Guangli, Qin Shiyi, Zhong Lianmei, Li Qing
    2025, 29 (28):  6127-6137.  doi: 10.12307/2025.470
    Abstract ( 216 )   PDF (1296KB) ( 219 )   Save
    BACKGROUND: Polyurethane materials, with their outstanding physicochemical properties, present extensive opportunities in the realm of biomedical engineering. Biomimetic design and functional modification of polyurethane nerve conduits are expected to further address the challenges of nerve regeneration and repair. 
    OBJECTIVE: To review the current status and advancements in the application of polyurethane-based nerve conduits in the field of peripheral nerve repair. 
    METHODS: The Chinese and English search terms consisted of “polyurethane, PU, polyurethane material, polyurethane biomaterials, nerve regeneration, peripheral nerve injury, nerve repair, nerve scaffold, nerve guidance conduit, nerve conduits.” The search was conducted in databases such as PubMed, Web of Science, CNKI (China National Knowledge Infrastructure), and WanFang for articles published from 2014 to 2024. Finally, 61 articles were included in the review.
    RESULTS AND CONCLUSION: Biomimetic composition is an effective strategy for enhancing the biological activity of polyurethane nerve conduits. Through structural biomimicry, polyurethane nerve conduits can be optimized to provide biological guidance cues for neural tissue regeneration. The biomechanically biomimetic polyurethane nerve conduits are likely to play a significant role in immune modulation and the promotion of axonal growth. By optimizing the conductive microenvironment of polyurethane materials, the reconstruction of neural electrical signal pathways can be facilitated. Polyurethane nerve conduits can serve as drug carriers, exerting anti-inflammatory and neuroprotective effects. Although the combined application of multiple design strategies can improve various aspects of damaged nerve function, the complex structure and dynamically changing pathophysiological microenvironment of nerves mean that nerve conduit design strategies still require refinement. Future advancements and innovations in nerve biomimetic design strategies hold promise for providing new insights and opportunities in the field of neural tissue engineering.
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    Platelet rich plasma versus hyaluronic acid in treatment of knee osteoarthritis: an overview of systematic reviews
    Zhang Yunyi, Liu Songtao, Xie Shaodong, Zhu Haifeng, Qian Guifeng, Huo Ming, Zhou Jie, Deng Zixuan
    2025, 29 (28):  6138-6145.  doi: 10.12307/2025.459
    Abstract ( 190 )   PDF (1141KB) ( 121 )   Save
    OBJECTIVE: The quality of systematic reviews/meta-analyses directly affects the reliability of clinical decision-making basis. Currently, there is no literature quality research on the systematic reviews/meta-analyses of platelet rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis both domestically and internationally. This article will comprehensively evaluate the methodological quality, reporting quality, and evidence quality of the systematic reviews/meta-analyses of platelet rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis.
    METHODS: Computer searches were conducted on CNKI, WanFang Data, VIP, CBM, PubMed, Embase, and The Cochrane Library. From the establishment of the database until January 24, 2024, all systematic reviews/meta-analyses treated with platelet rich plasma versus hyaluronic acid for knee osteoarthritis were collected. Two evaluators independently conducted literature screening and data extraction, and used the AMSTAR 2, PRISMA 2020, and GRADE systems to evaluate and summarize the methodological, reporting, and evidence quality of the included systematic reviews/meta-analyses.
    RESULTS: A total of 18 qualified systematic reviews/meta-analyses were included, and the results showed that the efficacy and safety of platelet rich plasma might be better than that of hyaluronic acid. The methodological quality of all 18 studies was extremely low; 4 reports had poor quality and relatively serious information defects, while 14 reports had moderate quality and some information defects. Among the 275 outcome measures of 16 systematic reviews/meta-analyses, there were 9 medium quality evidence, 90 low-quality evidence, and 176 extremely low-quality evidence, with no high-quality evidence. 
    CONCLUSION: At present, the quality of systematic reviews/meta-analyses literature on the treatment of knee osteoarthritis with platelet rich plasma versus hyaluronic acid is relatively low. In the future, the authors of the systematic reviews need to strictly follow the entries of quality evaluation tools such as AMSTAR 2 and PRISMA 2020 in terms of plan registration, research type explanation, retrieval strategy, exclusion list, research site and funding source, bias risk analysis, publication bias evaluation, and public information acquisition, and conduct evidence quality evaluation on the combined results of the systematic reviews/meta-analyses to provide more reliable and rigorous evidence-based basis for clinical practice.
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    Meta-analysis of wearable device interventions to promote physical activity in older adults
    Wang Jinfu, Yang Guan
    2025, 29 (28):  6146-6160.  doi: 10.12307/2025.469
    Abstract ( 276 )   PDF (3754KB) ( 153 )   Save
    OBJECTIVE: Although the potential benefits of wearable devices in enhancing the physical activity levels of the elderly have been recognized, the specific effects of these devices on this population have not yet been comprehensively and systematically assessed. The aim of this article is to systematically evaluate the effect of wearable device interventions on various physical activity-related indicators in the elderly, including moderate-to-vigorous physical activity, low-intensity physical activity, total physical activity, daily step count, and sedentary behavior.
    METHODS: A literature search was conducted through databases including PubMed, EMbase, Scopus, Ovid-Medline, The Cochrane Library, SPORTDiscus, CNKI, VIP, and WanFang from inception to March 10, 2024, to collect randomized controlled trials on the effect of wearable device interventions on physical activity in the elderly. The methodological quality of included studies was assessed using the Cochrane Risk of Bias tool. Data synthesis, subgroup analysis, forest plot creation, sensitivity analysis, publication bias assessment, and univariate meta-regression analysis were performed using Review Manager 5.2 and Stata 12.0 software.
    RESULTS: (1) A total of 43 articles, encompassing 5 194 participants, were included in the final analysis. (2) Meta-analysis results indicated that wearable device interventions significantly enhanced the daily step count (SMD=0.48, 95%CI: 0.33-0.62, P < 0.000 01), moderate-to-vigorous physical activity (SMD=0.29, 95%CI: 0.20-0.38, P < 0.000 01), low-intensity physical activity (SMD=0.17, 95%CI: 0.02-0.32, P=0.03), and total physical activity (SMD=0.15, 95%CI: 0.02-0.28, P=0.02) in the elderly. However, the intervention showed no significant effect on improving sedentary behavior (SMD=-0.08, 95%CI: -0.21-0.05, P=0.22). (3) Subgroup analysis revealed that comprehensive intervention strategies, interventions lasting ≤12 weeks, and the use of pedometers as intervention devices were more effective in promoting low-intensity physical activity and total physical activity among the elderly. Comprehensive intervention strategies, interventions lasting ≤12 weeks, and the use of accelerometers as intervention devices might be more effective in enhancing daily step count and moderate-to-vigorous physical activity. (4) Meta-regression results suggested that age (P=0.038) and health status (P=0.083) could be significant factors influencing heterogeneity in daily step count.
    CONCLUSION: Current evidence suggests that wearable device interventions have a positive role in promoting daily step count, moderate-to-vigorous physical activity, low-intensity physical activity, and total physical activity in the elderly. It is recommended to consider comprehensive intervention approaches, interventions lasting ≤12 weeks, and the selection of appropriate devices based on intervention goals when designing wearable device intervention programs. Nevertheless, further high-quality randomized controlled trials are needed to substantiate the effectiveness of interventions aimed at reducing sedentary behavior.
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