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    28 May 2024, Volume 28 Issue 15 Previous Issue    Next Issue
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    Effects of biological amniotic membrane on tendon adhesion and healing in ruptured Achilles tendon rats
    Yang Xiaoguang, Shi Yancheng, Ma Tao, Zhang Jimin, Zhang Wei
    2024, 28 (15):  2297-2301.  doi: 10.12307/2024.375
    Abstract ( 376 )   PDF (1287KB) ( 629 )   Save
    BACKGROUND: Achilles tendon adhesion after Achilles tendon injury can lead to decreased biomechanical properties, weakened healing ability, and ultrastructural changes of Achilles tendon, which further affects patients’ daily life and work ability. Therefore, how to effectively deal with and prevent Achilles tendon adhesion has become a hot and difficult problem in clinical treatment.
    OBJECTIVE: To analyze the effects of biological amniotic membranes on postoperative Achilles tendon adhesion, biomechanics, and ultrastructural changes in rats with Achilles tendon rupture.
    METHODS: Sixty 6-week-old SD rats were selected to establish bilateral Achilles tendon rupture models and divided into two groups (n=30 per group) by the random number table method. In the model group, the severed end of the tendon was sutured directly. In the amniotic membrane group, the biological amniotic membrane was wrapped around the broken anastomosis and fixed by a suture. The adhesion, biomechanics, morphology, and structure of the Achilles tendon and the expression of p38 and ERK1/2 protein were evaluated 1, 2, and 4 weeks after surgery.
    RESULTS AND CONCLUSION: (1) 1 week after operation, the Achilles tendon and peritendinous tissues of the two groups were mildly edema, and the adhesion of the Achilles tendon tissues in the model group was more obvious. 2 weeks after the intervention, the Achilles tendon and peritendinous tissues of the model group still had edema, and the adhesion degree between the Achilles tendon and the surrounding tissues was heavier than that of the amniotic membrane group. 4 weeks after operation, there was no edema around the Achilles tendon in both groups, and the healing was well. The adhesion degree of the Achilles tendon in the amniotic membrane group was less than that in the model group. The maximum tension of Achilles tendons in the amniotic membrane group was higher than that in the model group at 2 and 4 weeks after operation (P < 0.001). (2) Hematoxylin-eosin staining and transmission electron microscopy revealed that 1 week after operation, the tendon structure of rats of the two groups was disordered and the collagen fibers were sparsely arranged, in which the model group demonstrated obvious inflammatory reaction and adhesion to the Achilles tendon. Two weeks after operation, the model group still demonstrated obvious inflammatory response, adhesion of Achilles tendon, and irregular ordering of collagen fibers. The amniotic membrane group exhibited an orderly arrangement of collagen fibers and expansion of the endoplasmic reticulum of fibroblasts. At 4 weeks after operation, the collagen fibers of the Achilles tendon in the model group were thickened and disordered, and the rough endoplasmic reticulum was less in the fibroblasts, while the collagen fibers in the amniotic membrane group were ordered and thin, and the fibroblasts contained a large number of rough endoplasmic reticulum. (3) Four weeks after operation, western blot assay exhibited that the expressions of p38 and ERK1/2 protein in the Achilles tendon tissue of rats in the amniotic membrane group were lower than those in the model group (P < 0.05). (4) The results confirm that the biologic amniotic membrane can promote the healing and inhibit the adhesion of Achilles tendon after the operation of the ruptured Achilles tendon, which may be associated with the regulation of the MAPK/ERK signaling pathway.
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    Effect of nano-modified titanium surface with alkali heat treatment on early adhesion and growth of osteoblasts
    Gao Yan, Lin Xi, Liu Ying
    2024, 28 (15):  2302-2306.  doi: 10.12307/2024.402
    Abstract ( 356 )   PDF (1520KB) ( 457 )   Save
    BACKGROUND: Nanostructure modification of pure titanium surface is a hot research field of titanium implant surface treatment. 
    OBJECTIVE: To evaluate the effect of nano-modified titanium surface treated with alkali heat treatment on early adhesion and growth of osteoblasts.
    METHODS: Four-grade pure titanium sheets with a diameter of 15 mm and a thickness of 1.5 mm were taken and processed in three groups: the smooth treatment group was polished step by step with 250 mesh, 800 mesh, and 1 500 mesh silicon carbide sandpaper. In the sandblasting group, the smoothed titanium sheet was sandblasted with 100 μm Al2O3 particles at 0.45 MPa pressure, and then the acid etching was carried out. In the alkali heat treatment group, the smoothed titanium sheet was placed in the reactor, immersed in 10 mol/L NaOH solution, and heated in the oven at 100 °C for 12 hours. The surface morphology, roughness, and hydrophilicity of three groups of titanium sheets were measured. MG63 osteoblasts were inoculated on the surface of three groups of titanium tablets, and the adhesion of the cells was observed by immunofluorescence staining. 
    RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that the surface of titanium sheets in the smooth treatment group had uniform scratches; the surface of titanium sheets in the sandblasting group was uneven, and the surface of titanium sheets in the alkali heat treatment group had uniform nanoscale three-dimensional pore morphology. The roughness value of the titanium sheets in sandblasting and alkali heat treatment groups was higher than that in the smooth treatment group (P < 0.05), and the water contact angle was lower than that in the smooth treatment group (P < 0.05). (2) Immunofluorescence staining after 3 and 6 hours of inoculation of MG63 cells showed that the number of adhesion cells on the surface of the titanium sheet in the sandblasting group and alkali heat treatment group was higher than that in the smooth treatment group (P < 0.05). Immunofluorescence staining 12 hours after inoculation showed that compared with the smooth treatment group, the actin skeleton of cells on the surface of titanium sheets in the sandblasting group and alkali heat treatment group was more extended, and most cells extended stronger pseudopodia, which was conducive to subsequent intercellular signal transduction and intercellular interaction. (3) The results showed that the nanostructures with certain biological activity could be prepared on the surface of a titanium sheet by alkali heat treatment, which was conducive to the early adhesion of osteoblasts.
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    Moxibustion and reduced graphene oxide/cerium dioxide nanocomposites for repairing infectious wounds
    He Wei, Zhou Zheng, Wu Lingling, Wang Kai, Mu Caiyun
    2024, 28 (15):  2307-2314.  doi: 10.12307/2024.362
    Abstract ( 429 )   PDF (3574KB) ( 316 )   Save
    BACKGROUND: The repair process of skin trauma is complex and susceptible to infection, easy to lead to poor healing, is the current difficulty and hot spot in wound repair research, and has received extensive attention in the fields of traditional Chinese medicine and tissue engineering.
    OBJECTIVE: To investigate the effect of moxibustion and reduced graphene oxide/cerium oxide nanocomposite on promoting the healing of infectious wounds.
    METHODS: (1) Reduced graphene oxide/cerium dioxide nanocomposites with mass ratios of 2:1, 1:1 and 1:2 were synthesized by hydrothermal method. The resulting composites were recorded as G2C1, G1C1 and G1C2, respectively. The photothermal properties, cytotoxicity and antibacterial properties of the three kinds of materials were tested. After taking moxa sticks, three kinds of moxibustion distances were set (3.0-3.5 cm, recorded as moxibustion 1; 2.5-3.0 cm, recorded as moxibustion 2; 2.0-2.5 cm, recorded as moxibustion 3). Moxibustion was applied to the surface of human skin for 10 minutes to detect the photothermal properties. The antibacterial properties of moxibustion were tested at three different distance intervals. Simultaneously, the back body surface infrared imaging of rats with different mass concentrations of G1C1 material, moxibustion (three kinds of moxibustion distances) and moxibustion 2+G1C1 material was detected. (2) Sixty male Sprague-Dawley rats were selected to model the wound of Staphylococcus aureus infection. 48 hours later, they were randomly divided into 10 groups with 6 rats in each group: control group (did not receive any treatment), mupirocin group, moxibustion 2+G1C1 group, moxibustion 1 group, moxibustion 2 group, moxibustion 3 group and 60, 80, 100, and 120 μg/mL G1C1 groups (The G1C1 group was given 808 nm near-infrared laser irradiation for 10 min/time, and the G1C1 suspension was loaded on the wound surface before each treatment. Each group of moxibustion underwent in-situ suspension moxibustion, and the intervention time was 10 min/time. Moxibustion 2+G1C1 group was loaded with G1C1 suspension on the wound surface before each treatment, and moxibustion was suspended in situ with moxa strips, and the intervention time was 10 min/time). The frequency of treatment was 2 days once. Wound healing, wound colony count and repair were detected after 7 days of intervention.
    RESULTS AND CONCLUSION: (1) The three kinds of reduced graphene oxide/cerium dioxide nanocomposites had good photothermal properties, and the higher the mass concentration of the composites, the better the photothermal properties. The temperature of the moxibustion 2 group reached 47.6 °C for 10 minutes without causing thermal damage, which was more suitable for animal experiments. The results of co-culture with NIH-3T3 cells exhibited that 60, 80, and 100 μg/mL G1C1 had good biocompatibility. The results of a co-culture experiment with Staphylococcus aureus suspension displayed that G2C1, G1C1 and G1C2 had good antibacterial activity, among which G1C1 group demonstrated excellent antibacterial performance, and the antibacterial rate reached 100% when its mass concentration was 80 μg/mL. 60-120 μg/mL G1C1 could effectively remove Staphylococcus aureus biofilm, and the higher the material mass concentration, the better the removal effect. Moxibustion could also effectively remove Staphylococcus aureus biofilm, and the closer the moxibustion was, the better the removal effect. (2) Compared with the control group, the wound area of the mupirocin group, moxibustion 2 group, moxibustion 2+G1C1 group and 80, 100 μg/mL G1C1 groups was significantly reduced on day 7 of treatment, and the quality of wound repair was better. Mupirocin, G1C1, moxibustion and moxibustion 2+G1C1 could effectively remove the residual bacteria on the wound surface, and the higher the mass concentration of G1C1, the lower the residual bacteria. Among them, the wound repair efficiency and bacterial residue of 80 μg/mL G1C1 group and moxibustion 2 group were very similar, and the wound repair efficiency of both was better than that of mupirocin group. In addition, it was also observed that the combination of materials and moxibustion had a better ability to clear wound bacteria than that used alone. (3) The results confirm that moxibustion, reduced graphene oxide/cerium dioxide nanocomposites and their combination have good anti-infection and wound healing effects.
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    Polypyrrole-chitosan conductive composite hydrogel promotes recovery of cardiac function after ischemia-reperfusion injury
    Wang Xinzhu, Wang Qi, Lang Limin, He Sheng
    2024, 28 (15):  2315-2322.  doi: 10.12307/2024.372
    Abstract ( 510 )   PDF (3118KB) ( 278 )   Save
    BACKGROUND: Conductive biomaterials are considered potential candidates for transmitting electrical signals for myocardial repair. Combining cell-based or cell-free strategies with conductive biomaterials to replenish cardiomyocytes and/or restore electrical signaling pathways is a promising approach for cardiac repair.
    OBJECTIVE: To evaluate the effect of polypyrrole-chitosan conductive composite hydrogel on cardiac function in rats with myocardial ischemia-reperfusion injury.
    METHODS: The polypyrrole-chitosan conductive composite hydrogel was prepared by chemical oxidative polymerization. The micromorphology, biocompatibility and conductivity of the hydrogels were characterized. Thirty adult SD rats were selected to establish a myocardial ischemia-reperfusion injury model by clamping the left anterior descending branch of the heart and then releasing it. After 21 days of modeling, the rats were divided into three groups by the random number table method: Normal saline was injected into the left ventricular infarction area and infarction margin area in the blank group. Chitosan hydrogel was injected into the left ventricular infarction area and infarction margin area in the ordinary hydrogel group. The polypyrrole-chitosan conductive composite hydrogel was injected into the left ventricular infarction area and infarction margin area, with 10 rats in each group. The corresponding time points after modeling were set, and cardiac mechanical function (echocardiogram, pressure-volume analysis), cardiac electrophysiology (electrocardiogram, programmed electrical stimulation, optical mapping technology, microelectrode array technology, eight-lead electrocardiogram, and electrical resistivity of the scar area) and cardiac histology were detected. 
    RESULTS AND CONCLUSION: (1) There were a lot of pores on the surface of the conductive composite hydrogel, and the conductivity was (3.19±0.03)×10-3 mS/cm, which had good biocompatibility co-cultured with smooth muscle cells. (2) After 105 days of modeling, echocardiogram and pressure-volume analysis showed that compared with the blank group and the ordinary hydrogel group, the conductive composite hydrogel could significantly improve the contractile function of the heart of rats with myocardial ischemia-reperfusion injury. The results of electrocardiogram, programmed electrical stimulation, optical mapping technology, microelectrode array technology, eight-lead electrocardiogram, and electrical resistivity of the scar area examination at 105 days after modeling displayed that, compared with the blank group and the ordinary hydrogel group, the conductive composite hydrogel could significantly improve the electrical conduction function of the heart of rats with myocardial ischemia-reperfusion injury and reduce the occurrence of arrhythmia. Masson staining of heart tissue at 105 days after modeling exhibited that there were different degrees of fibrosis in the myocardial infarction area of the three groups. Compared with the normal saline group and the ordinary hydrogel group, the conductive hydrogel group had more normal myocardial tissue and less fibrosis in the myocardial infarction area. (3) The results verify that polypyrrole-chitosan conductive composite hydrogel may promote the repair of infarcted heart after ischemia-reperfusion injury by increasing the electrical conduction velocity of infarct scar area tissue, increasing scar thickness, enhancing synchronous cardiac contraction, and reducing damaged tissue. 
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    Visualization analysis of magnetically controlled growing rod in treatment of spinal deformities
    Ye Xiaolong, Ma Yuan
    2024, 28 (15):  2323-2329.  doi: 10.12307/2024.379
    Abstract ( 274 )   PDF (3177KB) ( 759 )   Save
    BACKGROUND: With the continuous improvement and progress of the magnetically controlled growing rod technology in the field of the treatment of spinal deformities, numerous studies have been put into this field, but the main research status, hot spots, and development trends are not clear enough.
    OBJECTIVE: Based on bibliometrics, this paper discusses the quality and quantity of articles in the field of using magnetically controlled growing rods to treat spinal deformities from different countries, aiming to clarify the global development trend of magnetically controlled growing rods and evaluate the research productivity, research trends, and research hotspots in the world.
    METHODS: The articles published from 1998 to 2023 were retrieved mainly based on the Web of Science database. CiteSpace 5.8 and VOSviewer 1.6.19 software were used to analyze the data and generate a visual knowledge map. The following parameters were evaluated for all studies: the total number of published papers, centrality, h index, the contribution of countries, authors, and journals, and the trend and hot spots were explored through the analysis of 
    co-citation, highly cited literature, and literature keyword explosion.
    RESULTS AND CONCLUSION: (1) Finally, 138 articles were included. From 2009 to 2020, the number of published articles in this field gradually increased. The United States has the largest number of articles (53, 37.32%), and the United States has the highest h index and centrality of articles. (2) The results of keyword analysis showed that: the top ten keywords, such as early-onset scoliosis, surgery, complications, and so on, objectively and truly reflected the current situation and hot spots of magnetically controlled growing rod in the field of spinal deformity treatment. In recent years, the research focus in this field is the treatment failure caused by risk factors such as the pull-out of the magnetically controlled growing rod, implantation failure, and rod fracture, the accurate use of the corresponding medical classification, the monitoring and treatment of complications such as quality of life and cerebral palsy. (3) The co-citation results showed that: combined with the innovative and effective research of the magnetically controlled growing rod technology, the classification application of spinal deformity and the monitoring and treatment of related complications may be the research trend in this field. (4) Many highly cited articles further emphasized the therapeutic effect of magnetically controlled growing rod technology, providing an effective new idea and technical support for the field of spinal deformity correction. (5) The results of literature keyword explosion analysis demonstrate that the risk factors, medical classification, quality of life, and cerebral palsy of the application of magnetically controlled growing rods may become the research frontier in this field. (6) It can be seen that the application of magnetically controlled growing rod technology in the classification of spinal deformities and the in-depth study of related complications are the development trend in this field, but to further understand the effectiveness and safety of magnetically controlled growing rod technology in the treatment of spinal deformities, we still need long-term follow-up evidence. The overall research level of this field has steadily improved in recent years, but there are also problems such as the small number of high-quality articles and the unbalanced development of research in various regions.
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    Ultrasound-optimized hydrogel scaffold used to promote transdermal delivery of gold nanoparticles
    Guo Yuxin, Wang Hao, Li Mingqi, Chen Yueying, Pan Juhong, Huang Xin, Wang Zhiwen, Zhou Qing
    2024, 28 (15):  2330-2337.  doi: 10.12307/2024.377
    Abstract ( 353 )   PDF (3084KB) ( 338 )   Save
    BACKGROUND: Gold nanoparticles are of great significance in the development of multifunctional transdermal drug delivery systems. Smaller gold nanoparticles can penetrate the dermis through the intercellular pathway, but are limited to their easy agglomeration and colloidal morphology, which makes it difficult to exert effects on low delivery efficiency.
    OBJECTIVE: To develop an ultrasound-optimized hydrogel delivery system by combining phase change nanodroplets with bio-adhesive hydrogel for percutaneous delivery of gold nanoparticles.
    METHODS: The ultrasound-responsive nanodroplets loaded with gold nanoparticles were prepared by the emulsion solvent evaporation method and loaded into the polydopamine-modified methylacryloyl gelatin hydrogel to prepare a composite hydrogel scaffold. The structure and chemical composition of the ultrasound-responsive nanogold carrier were characterized. The microstructure, porosity, permeability, rheology, in vitro hemostasis, and antibacterial properties of the composite hydrogel were characterized. The cell compatibility of the hydrogel scaffold was evaluated by live/dead staining, and the optimization effects of low-intensity pulsed ultrasound on the permeability, porosity, and mechanical properties of hydrogel were evaluated.
    RESULTS AND CONCLUSION: (1) Transmission electron microscopy and ultraviolet-visible spectroscopy proved the successful construction of nanogold carriers. The particle size and potential results demonstrated that the synthesized nanoscaled ultrasonic responsive carrier had good stability. (2) Live/dead cell staining proved that the prepared composite hydrogel scaffold had certain biocompatibility. (3) Scanning electron microscopy exhibited that the prepared composite hydrogel scaffold had a porous network structure, and numerous pores of about 2 μm appeared inside the macropores after the addition of nanodroplets and ultrasonic irradiation. The permeability experiment displayed that low-intensity pulsed ultrasound could optimize the porosity and permeability of hydrogel materials. The hemostatic performance of the composite hydrogel scaffold was better than that of the hemostatic sponge and polydopamine@methylacrylylated gelatin hydrogel scaffold. Under the irradiation of low-intensity pulsed ultrasound, the composite hydrogel scaffolds had good antioxidant effects and antibacterial properties. (4) Thermal imaging results manifested that gold nanoparticles were encapsulated in ultrasound-responsive nanobubbles, and more uniform dispersion could be obtained under ultrasonic excitation. (5) The results of the mechanical property test demonstrated that the storage modulus of the hydrogel increased before and after loading gold nanoparticles-nanodroplets, which showed stronger mechanical properties. The elongation at break was 122%, and the ductility was better than that without gold nanoparticles-nanodroplets (P < 0.05). (6) These findings indicate that the composite hydrogel scaffold has good biocompatibility, antibacterial property, oxidation resistance, and hemostatic effect.
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    Mechanism of black phosphorus regulating oxidative stress-inflammation cascade in retarding intervertebral disc degeneration
    Kou Yu, Gu Yong, Chen Liang
    2024, 28 (15):  2338-2345.  doi: 10.12307/2024.250
    Abstract ( 357 )   PDF (3135KB) ( 1918 )   Save
    BACKGROUND: Oxidative stress plays a critical role in intervertebral disc degeneration. As a reducing material with good biocompatibility, black phosphorus quantum dots have the potential to resist oxidative stress and retard intervertebral disc degeneration.  
    OBJECTIVE: To evaluate the effect of black phosphorus quantum dots on scavenging reactive oxygen species in the microenvironment of an intervertebral disc through in vivo and in vitro experiments, and further explore the role of black phosphorus quantum dots in Nrf2/ARE pathway and intervertebral disc inflammation. 
    METHODS: Black phosphorus quantum dots were prepared by a liquid exfoliation technique. (1) In vitro experiment: The nucleus pulposus cells of SD rats were isolated and extracted, and the passages 2-4 nucleus pulposus cells were cocultured with different solutions, including F12-DMEM medium (blank group), black phosphorus quantum dot solution, hydrogen peroxide solution, hydrogen peroxide+black phosphorus quantum dot solution, hydrogen peroxide+black phosphorus quantum dot+Nrf2 specific inhibitor ML385 solution. Cell live/dead staining and intracellular reactive oxygen species, mitochondrial membrane potential and western blot assay were performed respectively. (2) In vivo experiment: Thirty SD rats were randomly divided into sham operation, puncture and puncture + black phosphorus groups, with 10 rats in each group. A Co7-10 intervertebral disc degeneration model was established using intervertebral disc puncture in the puncture group and the puncture+black phosphorus group. Black phosphorus quantum dot solution was injected in the intervertebral disc after a puncture in the puncture+black phosphorus group. The intervertebral disc tissue imaging and histological staining were evaluated at 4 and 8 weeks after surgery. 
    RESULTS AND CONCLUSION: (1) In vitro experiment: Live/dead staining revealed that the black phosphorus quantum dots had good biocompatibility, were non-toxic to cells, and had a protective effect on nucleus pulposus cells under oxidative stress. Intracellular reactive oxygen species and JC-1 fluorescent probes showed that black phosphorus quantum dots could regulate the reduction of mitochondrial membrane potential caused by oxidative stress in nucleus pulposus cells and protected cells from hydrogen peroxidation-induced intracellular oxidative stress. Western blot analysis showed that compared with the blank group, the protein expressions of Nrf2, heme oxygenase 1, quinone oxidoreductase and type II collagen were decreased in the hydrogen peroxide group (P < 0.05), while the protein expressions of tumor necrosis factor α, interleukin 1β, matrix metalloproteinase 13 and p65 were increased (P < 0.05). The addition of black phosphorus quantum dots could reverse the inhibitory effect of hydrogen peroxide on the Nrf2 pathway and reduce the inflammatory response caused by oxidative stress, but NrF2-specific inhibitors could cancel this effect. (2) In vivo experiment: X-ray and MRI demonstrated that at 4 and 8 weeks after surgery, the intervertebral disc height and water content of nucleus pulposus in the puncture group were lower than those in the sham operation group (P < 0.05), and the intervertebral disc height and water content of nucleus pulposus in the puncture+black phosphorus group were higher than those in the puncture group (P < 0.05). Histological staining exhibited that the degree of intervertebral disc degeneration in the puncture+black phosphorus group was less than that in the puncture group, and the expression of heme oxygenase 1 protein was higher than that in the puncture+black phosphorus group. (3) Our results have indicated that black phosphorus quantum dots can exert an antioxidant effect and delay intervertebral disc degeneration by regulating Nrf2/ARE pathway. 
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    Effects of nano-zirconium dioxide on osteogenic differentiation of ectomesenchymal stem cells in nasal mucosa
    Bian Lu, Xia Dandan, Qian Yuan, Shi Wen, Que Yunduan, Lyu Long, Xu Aihua, Shi Wentao
    2024, 28 (15):  2346-2350.  doi: 10.12307/2024.409
    Abstract ( 338 )   PDF (1920KB) ( 97 )   Save
    BACKGROUND: Nano-zirconium dioxide has good application potential in the field of bone tissue repair. Studying the effect of nano-zirconium dioxide on osteogenic differentiation will help to promote the clinical application of nano-zirconium dioxide in the treatment of bone defects.  
    OBJECTIVE: To explore the effect of nano-zirconium dioxide on the osteogenic differentiation of ectomesenchymal stem cells in the nasal mucosa.
    METHODS: Ectomesenchymal stem cells derived from rat nasal mucosa were isolated and cultured, and the biotoxicity of nano-zirconium dioxide to the cells was detected by CCK-8 assay. The biosafety concentration was selected according to the cytotoxicity, and the cells were randomly divided into a control group, a nano-zirconium dioxide group, and a nano-hydroxyapatite group. Osteogenic differentiation of cells was directionally induced in each group. On day 7 of induced differentiation, alkaline phosphatase staining was performed. qRT-PCR and western blot assay were used to detect the expression of early osteogenic markers (Runx2 and Osx). On day 21 of induced differentiation, alizarin red staining was conducted. qRT-PCR and western blot assay were utilized to determine the expression levels of late osteogenic markers (OPN and OCN). 
    RESULTS AND CONCLUSION: (1) The median lethal concentration of nano-zirconium dioxide on ectomesenchymal stem cells in nasal mucosa was 0.6 mg/mL. In the experiment, the mass concentration of 200 μg/mL was selected for intervention. Zirconium dioxide had no significant effect on the proliferation of the cells. (2) Compared with the control group, the alkaline phosphatase staining of the cells in the nano-zirconium dioxide group was more obvious and the level of cell mineralization was higher, but there was no significant difference compared with the nano-hydroxyapatite. (3) Compared with the control group, the expression of bone-related genes and proteins increased significantly, but there was no significant difference compared with nano-hydroxyapatite. (4) The results show that nano-zirconium dioxide has good biological safety and can promote the osteogenic differentiation of ectomesenchymal stem cells in the nasal mucosa. This promoting effect is equivalent to that of nano-hydroxyapatite. 
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    Cytocompatibility of electrospun polyvinylidene fluoride piezoelectric bionic periosteum
    Wei Suiyan, Cao Yijing, Zhao Shuai, Li Dongyao, Wei Qin, Xu Yan, Xu Guoqiang
    2024, 28 (15):  2351-2357.  doi: 10.12307/2024.270
    Abstract ( 378 )   PDF (1474KB) ( 156 )   Save
    BACKGROUND: Polyvinylidene fluoride (PVDF) with piezoelectric properties, good biocompatibility and nontoxicity make it a suitable candidate for periosteal repair. 
    OBJECTIVE: To evaluate the cytotoxicity of PVDF bionic periosteum by electrospinning with zinc and magnesium ions in vitro.
    METHODS: Pure PVDF, zinc-doped PVDF, magnesium-doped PVDF and Zinc-magnesium ion PVDF piezoelectric bionic periosteum were prepared by electrospinning technology, respectively. They were named PVDF, PVDF-Zn, PVDF-Mg and PVDF-Zn-Mg, in which the mass fraction of zinc and magnesium ions were all 1%. Osteoblasts and vascular endothelial cells were co-cultured with four groups of bionic periosteum. Cell compatibility of bionic periosteum was determined by alkaline phosphatase staining, CD31 immunofluorescence staining, and scanning electron microscopy.
    RESULTS AND CONCLUSION: (1) Osteoblasts: Alkaline phosphatase staining after 7 days of culture showed that the PVDF-Zn group secreted more alkaline phosphatase than the other three groups. Under a scanning electron microscopy, after 1 day of culture, the cells had a certain spread on the surface of PVDF-Mg and PVDF-Zn-Mg bionic periosteum, and the pseudopod extended to all sides. On day 3, the cell edge of each group extended pseudopods to the material. By days 5 and 7, the cells were fully spread, well grown and firmly covered the surface of the fibers, and the cellular pseudopods extended around and into the interstitial space of the fibers. CCK-8 assay showed that the cell proliferation on the bionic periosteum of each group showed an increasing trend over time and the relative proliferation rate of cells at 1, 3, 5, and 7 days was ≥75%, and the cytotoxicity was ≤ grade 1. (2) Vascular endothelial cells: CD31 immunofluorescence staining for 3 days showed that the cells adhered and spread well on the bionic periosteum of each group and connected with each other, and the number of cells in the PVDF-Zn-Mg group was more than that in the other three groups. Under scanning electron microscope, the cells began to adhere to the surface of each group of fibers after 1 and 3 days of culture. On day 5, the cells were well spread on the surface of the fibers and extended obvious pseudopods. On day 7, the cells on the PVDF-Mg and PVDF-Zn-Mg bionic periosteum grew in multiple layers and extended the pseudopod into the fibrous void. CCK-8 assay showed that the cell proliferation on the bionic periosteum of each group showed a downward trend over time, and the relative proliferation rate of cells at 1, 3, 5 and 7 days was ≥125%, and the cytotoxicity was grade 0. (3) The results showed that Zn-Mg electrospun PVDF piezoelectric bionic periosteum had good cytocompatibility.
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    Visualization analysis of hot spots and trends in material biomechanics
    Hong Jing, Lu Congfei, Huang Chenbin, Jiang Qian, Liu Jingxiong
    2024, 28 (15):  2358-2363.  doi: 10.12307/2024.407
    Abstract ( 273 )   PDF (1683KB) ( 254 )   Save
    BACKGROUND: Material biomechanics is the investigation of the mechanical microenvironment of biomaterials through a material science approach, which belongs to the frontier discipline of sustainable development. 
    OBJECTIVE: To explore the current research hotspots and development trends of material biomechanics and provide theoretical references for subsequent research. 
    METHODS: Based on CiteSpace bibliometric software, we generated keyword co-occurrence and clustering, emergent word detection, and other knowledge maps based on 3 182 material biomechanics literature in the Web of Science core database during 2012-2022 for visualization analysis. 
    RESULTS AND CONCLUSION: The number of research articles on the biomechanics of materials has been increasing in the last decade, and the United States, China, and Germany are the top three countries in terms of the number of articles published, and the research is mainly concentrated on major universities and research institutions, with significant aggregation. Material biomechanics research mainly involves the disciplines of material science, biomedical engineering, and kinesiology. Finite element analysis, material properties, mechanical performance of biomaterials, and molecular biomechanics are the focus of scholars’ attention and research. At present, the research in the field of material biomechanics focuses on the use of finite element analysis to calculate the mechanical response of different biomedical materials under different conditions of loading and mechanical properties for the prevention of sports diseases, surgical planning, and postoperative rehabilitation. The application of inorganic materials and the mode of transport of molecular signals may be the prospect of future research. 
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    Preparation and characterization of a novel self-assembled polypeptide hydrogel sustainably releasing platelet-rich plasma growth factors
    Qi Fengying, Wang Lei, Li Dongdong, Yan Shaoduo, Liu Kun, Zheng Yizhe, He Zixin, Yi Xiaoyang, Wang Donggen, Fu Qiuxia, Liang Jun
    2024, 28 (15):  2364-2370.  doi: 10.12307/2024.369
    Abstract ( 500 )   PDF (1443KB) ( 302 )   Save
    BACKGROUND: Due to the sudden release and the rapid removal by proteases, platelet-rich plasma hydrogel leads to shorter residence times of growth factors at the wound site. In recent years, researchers have focused on the use of hydrogels to encapsulate platelet-rich plasma in order to improve the deficiency of platelet-rich plasma hydrogels.
    OBJECTIVE: To prepare self-assembled polypeptide-platelet-rich plasma hydrogel and to explore its effects on the release of bioactive factors of platelet-rich plasma. 
    METHODS: The self-assembled polypeptide was synthesized by the solid-phase synthesis method, and the solution was prepared by D-PBS. Hydrogels were prepared by mixing different volumes of polypeptide solutions with platelet-rich plasma and calcium chloride/thrombin solutions, so that the final mass fraction of polypeptides in the system was 0.1%, 0.3%, and 0.5%, respectively. The hydrogel state was observed, and the release of growth factors in platelet-rich plasma was detected in vitro. The polypeptide self-assembly was stimulated by mixing 1% polypeptide solution with 1% human serum albumin solution, so that the final mass fraction of the polypeptide was 0.1%, 0.3%, and 0.5%, respectively. The flow state of the liquid was observed, and the rheological mechanical properties of the self-assembled polypeptide were tested. The microstructure of polypeptide (mass fraction of 0.1% and 0.001%) -human serum albumin solution was observed by scanning electron microscope and transmission electron microscope.
    RESULTS AND CONCLUSION: (1) Hydrogels could be formed between different volumes of polypeptide solution and platelet-rich plasma. Compared with platelet-rich plasma hydrogels, 0.1% and 0.3% polypeptide-platelet-rich plasma hydrogels could alleviate the sudden release of epidermal growth factor and vascular endothelial growth factor, and extend the release time to 48 hours. (2) After the addition of human serum albumin, the 0.1% polypeptide group still exhibited a flowing liquid, the 0.3% polypeptide group was semi-liquid, and the 0.5% polypeptide group stimulated self-assembly to form hydrogel. It was determined that human serum albumin in platelet-rich plasma could stimulate the self-assembly of polypeptides. With the increase of the mass fraction of the polypeptide, the higher the storage modulus of the self-assembled polypeptide, the easier it was to form glue. (3) Transmission electron microscopy exhibited that the polypeptide nanofibers were short and disordered before the addition of human serum albumin. After the addition of human serum albumin, the polypeptide nanofibers became significantly longer and cross-linked into bundles, forming a dense fiber network structure. Under a scanning electron microscope, the polypeptides displayed a disordered lamellar structure before adding human serum albumin. After the addition of human serum albumin, the polypeptides self-assembled into cross-linked and densely arranged porous structures. (4) In conclusion, the novel polypeptide can self-assemble triggered by platelet-rich plasma and the self-assembly effect can be accurately adjusted according to the ratio of human serum albumin to polypeptide. This polypeptide has a sustained release effect on the growth factors of platelet-rich plasma, which can be used as a new biomaterial for tissue repair.  
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    Repair of chronic tympanic membrane perforation by bone marrow mesenchymal stem cells-loaded high-porosity polycaprolactone-collagen nanofiber membrane scaffolds
    Li Shuo, Hu Haolei, Yang Jie, Xu Tao, Yin Gang, Li Yi
    2024, 28 (15):  2371-2377.  doi: 10.12307/2024.404
    Abstract ( 226 )   PDF (1764KB) ( 256 )   Save
    BACKGROUND: In recent years, there have been many novel tympanic membrane repair materials, including patches and 3D-printed scaffolds. However, the tympanic membrane repaired by these materials is different from the natural tympanic membrane in terms of thickness and internal structure.
    OBJECTIVE: To explore the efficacy of bone marrow mesenchymal stem cells-loaded high-porosity polycaprolactone/collagen nanofiber membrane scaffolds in repairing chronic tympanic membrane perforation.
    METHODS: Polycaprolactone, polycaprolactone-collagen, and high-porosity polycaprolactone-collagen nanofiber membranes were prepared by electrospinning technology, and the surface morphology, porosity and cell compatibility of the scaffolds were characterized. The tympanic membrane perforation model of 50 male SD rats was established by puncturing the posterior lower part of both eardrums with a sterile 23-measure needle combined with mitomycin C and hydrocortisone. After 12 weeks of modeling, the rats were divided into five groups by the random number table method. The blank control group did not receive any treatment. In the other four groups, polycaprolactone nanofiber membrane (polycaprolactone group), polycaprolactone-collagen nanofiber membrane (polycaprolactone-collagen group), high-porosity polycaprolactone-collagen nanofiber membrane (high-porosity polycaprolactone-collagen group) and high-porosity polycaprolactone-collagen nanofiber membrane containing bone marrow mesenchymal stem cells (high-porosity polycaprolactone-collagen group) were implanted at the perforation of the tympanic membrane, respectively. Each group consisted of 10 animals. The healing of the tympanic membrane was examined by otoendoscopy after 1, 2, 3 and 4 weeks of stent implantation. Hematoxylin-eosin staining, Masson staining, and Ki-67 immunohistochemical staining were performed on the tympanic membrane after 4 weeks of implantation. 
    RESULTS AND CONCLUSION: (1) Scaffold characterization: Scanning electron microscopy showed that compared with other nanofiber membranes, the high-porosity polycaprolactone-collagen nanofiber membranes had more orderly nanofiber structure, larger surface pore size, and higher porosity (P < 0.001). Live/dead staining showed that bone marrow mesenchymal stem cells adhered well on the three scaffolds, and the number of living cells on the high-porosity polycaprolactone-collagen nanofiber membrane was more than that on the other two scaffolds. Almarin staining showed that the proliferation rate of bone marrow mesenchymal stem cells on the high-porosity polycaprolactone-collagen nanofiber membrane was higher than that of the other two fiber membranes. (2) Animal experiments: Except for the blank control group, the tympanic membrane of the other four groups healed gradually with the extension of the time of fibrous membrane implantation, among which the healing speed of the cell-loaded high-porosity polycaprolactone-collagen group was the fastest. Hematoxylin-eosin staining, Masson staining, and Ki-67 immunohistochemical staining showed that the tympanic membrane of rats in the cell-carrying high-porosity polycaprolactone-collagen group was moderate in thickness and a three-layer structure with uniform collagen fiber layers, similar to the normal tympanic membrane, and the repair quality of tympanic membrane was better than that of other fiber membrane groups. (3) The results showed that the high-porosity polycaprolactone-collagen nanofiber membrane containing bone marrow mesenchymal stem cells could not only rapidly repair the perforation of the tympanic membrane, but also the newly healed tympanic membrane was similar to normal tympanic membrane in structure and thickness.
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    Preparation of collagen-binding domain-bone morphogenetic protein 2-collagen cartilage scaffold and its chondrogenic induction
    Wang Buyu, Zhang Yong, Ruan Shiqiang, Deng Jiang
    2024, 28 (15):  2378-2384.  doi: 10.12307/2024.403
    Abstract ( 409 )   PDF (1372KB) ( 132 )   Save
    BACKGROUND: Natural bone morphogenetic protein 2 disperses and degrades rapidly in vivo, reducing local concentration and therapeutic efficacy. Simply combining bone morphogenetic protein 2 with tissue engineering scaffolds could not stay in vivo for a long time, making it difficult to achieve good sustained and controlled release effects.
    OBJECTIVE: To prepare and test the biological properties and chondrogenic induction effect of collagen-binding domain-bone morphogenetic protein 2-collagen cartilage scaffold. 
    METHODS: SD rat tail collagen was extracted and a collagen cartilage scaffold was prepared using a vacuum freeze-drying machine chemical crosslinking method. The plasmid expressing collagen-binding domain-bone morphogenetic protein 2 was constructed by rapid cloning C112 homologous recombination, constructed by genetic engineering, and introduced into E. coli, and then collagen-binding domain-bone morphogenetic protein 2 was isolated and purified. Natural bone morphogenetic protein 2 and collagen-binding domain-bone morphogenetic protein 2 were combined with collagen cartilage scaffolds, respectively, to detect the release level of bone morphogenetic protein 2 in the scaffolds. The biocompatibility of collagen-binding domain-bone morphogenetic protein 2-collagen cartilage scaffold was detected by CCK-8 assay and F-Actin staining. Bone marrow mesenchymal stem cells were implanted on two kinds of collagen cartilage scaffolds for chondrogenic induction, and their chondrogenic induction activity was tested.    
    RESULTS AND CONCLUSION: (1) The binding rate of collagen-binding domain-bone morphogenetic protein 2 to collagen cartilage scaffolds was higher than that of natural bone morphogenetic protein 2 (P < 0.05). After being immersed in PBS for 7 days in vitro, the release of bone morphogenetic protein 2 in the collagen-binding domain bone morphogenetic protein 2-collagen cartilage scaffold was smaller than that in the natural bone morphogenetic protein 2-collagen cartilage scaffold (P < 0.05). The results of the CCK-8 assay and F-Actin staining showed that the collagen-binding domain-bone morphogenetic protein 2-collagen cartilage scaffold had no obvious cytotoxicity and had good biocompatibility. (2) After 14 days of chondrogenic induction, ELISA detection demonstrated that the expressions of agglutincan and type II collagen A1 in the collagen-binding domain-bone morphogenetic protein 2-collagen cartilage scaffold group were higher than those in the natural bone morphogenetic protein 2-collagen cartilage scaffold group (P < 0.05). Under scanning electron microscopy, more bone marrow mesenchymal stem cells were observed on the inner wall of the pores of the two groups of scaffolds, and the cell morphology and size were the same, and the cells were closely arranged, without cell fragmentation or abnormal morphology. (3) The results indicate that the collagen-binding domain-bone morphogenetic protein 2-collagen cartilage scaffold has good biological properties and chondrogenic induction activity. 
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    Percutaneous transforaminal endoscopic discectomy combined with platelet-rich plasma in treatment of lumbar disc herniation
    Li Tusheng, Ding Yu, Jiang Qiang, Zhang Hanshuo, Liu Jiang
    2024, 28 (15):  2385-2390.  doi: 10.12307/2024.401
    Abstract ( 355 )   PDF (1135KB) ( 235 )   Save
    BACKGROUND: Platelet-rich plasma can promote the repair and regeneration of intervertebral disc tissue. Percutaneous transforaminal endoscopic discectomy is widely used in the treatment of lumbar disc herniation. In recent years, more and more scholars have focused on the combined treatment of lumbar disc herniation with the two techniques in order to achieve a better patient prognosis. 
    OBJECTIVE: To investigate the clinical safety and effectiveness of percutaneous transforaminal endoscopic discectomy combined with platelet-rich plasma in the treatment of lumbar disc herniation.  
    METHODS: The clinical data of 58 patients with lumbar disc herniation who met the inclusion and exclusion criteria at Sixth Medical Center of PLA General Hospital from June 2017 to May 2018 were retrospectively analyzed. Among them, 29 patients underwent percutaneous transforaminal endoscopic discectomy combined with platelet-rich plasma (observation group), and the remaining 29 patients underwent percutaneous transforaminal endoscopic discectomy only (control group). Visual Analogue Scale score for back and leg pain, lumbar JOA score, and Oswestry Disability Index were evaluated preoperatively, at 3, 6, and 12 months postoperatively, and at the last follow-up. Intervertebral space height, nucleus pulposus to cerebrospinal fluid signal strength ratio, and intervertebral disc Pfirrmann grading were measured preoperatively, at 6 and 12 months postoperatively, and at the last follow-up. The modified MacNab criteria were used to assess excellent and good rate of curative effect at the last follow-up.
    RESULTS AND CONCLUSION: (1) The Visual Analogue Scale score for back and leg pain, JOA score, and Oswestry Disability Index of the two groups postoperatively were significantly improved compared with those preoperatively (P < 0.05). Visual Analogue Scale score and Oswestry Disability Index were lower in the observation group than those in the control group at 3 and 6 months postoperatively (P < 0.05). The JOA score was higher in the observation group than that in the control group at 3 and 6 months postoperatively (P < 0.05). (2) The nucleus pulposus to cerebrospinal fluid signal strength ratio was higher in the observation group than that in the control group at the last follow-up (P < 0.05). Pfirrmann grading of the intervertebral discs was better in the observation group than that in the control group (P < 0.05). The excellent and good rate was 93% in the observation group and 83% in the control group, and the difference was not statistically significant (P > 0.05). (3) These findings indicate that percutaneous transforaminal endoscopic discectomy combined with platelet-rich plasma in the treatment of lumbar disc herniation has satisfactory clinical efficacy and can delay the degeneration of the intervertebral disc to a certain extent.
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    Comparison and analysis of modeling heart valve bracket based on magnetic resonance imaging
    Cui Yiwen, Yuan Quan, Liu Jikai
    2024, 28 (15):  2391-2397.  doi: 10.12307/2024.376
    Abstract ( 287 )   PDF (4415KB) ( 139 )   Save
    BACKGROUND: Currently, artificial valves used in heart valve operations include biological valves and mechanical valves. The design and processing of the biological valve bracket determine the shape of the biological valves, which in turn determines their service life.
    OBJECTIVE: Various lobe and bracket models were created based on the spatial geometric equation. Through a comparison of the deformation and stress distribution of various lobe and bracket models, a more rational bracket model was derived. Subsequently, 3D printing technology was utilized to produce a solid model.
    METHODS: According to the geometric and mathematical models of the heart valve leaf and valve bracket, parabolic and ellipsoidal heart valve bracket models were created. Three-dimensional modeling was used to design the heart valve bracket. Two-way fluid-structure coupling analysis was conducted to analyze the force and deformation of the valve bracket in the blood flow field. An appropriate printing method and materials were selected to achieve 3D printing of the heart valve bracket. 
    RESULTS AND CONCLUSION: The distribution rules of deformation, maximum principal stress, and maximum shear stress of the parabolic bracket and ellipsoidal bracket are the same. The deformation and stress of the ellipsoidal bracket were greater than those of the parabolic bracket. The distribution law of maximum principal stress and maximum shear stress was mainly concentrated in the joint part of the lobe and bracket. The total deformation, maximum principal stress, and maximum shear stress of the bracket decrease with the increase of the bracket diameter.
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    Biomaterials and pore characteristics of tendon tissue engineering scaffolds
    Wang Xiaolong, Huang Haoran, Zhang Zhongxin, Wang Limin, Hu Yongcheng
    2024, 28 (15):  2398-2403.  doi: 10.12307/2024.388
    Abstract ( 334 )   PDF (797KB) ( 256 )   Save
    BACKGROUND: With the increasing number of tendon transplantation surgeries for tendon injuries, the demand for tendon tissue engineering scaffolds is increasing. Research has found that good pore size and porosity of implants contribute to tissue healing.
    OBJECTIVE: To review the types of materials currently published for tendon tissue engineering scaffolds and investigate the correlation between various tendon tissue engineering scaffold materials and pores. 
    METHODS: Articles were retrieved on PubMed, Embase, and Web of Science databases, using keywords “tendon” or “ligament” and “tissue scaffold” as well as “porosity” or “permeability”. A total of 84 articles meeting the criteria were included to summarize, discuss and anticipate future development directions.
    RESULTS AND CONCLUSION: The materials used in the research of tendon tissue engineering are mainly divided into two categories: natural tendon scaffold materials and artificial synthetic tendon scaffold materials. Natural scaffold materials include autologous tendons, allogeneic tendons, and xenogeneic tendons. Autogenous tendons and allogeneic tendons have been used in clinical practice for many years. During the preparation of allogeneic tendons and animal experiments, it was found that the process of acellular disinfection resulted in an increase in the pore size and porosity of both types of tendons, but the specific reasons and mechanisms have not been further studied. There are many types of artificial tendon scaffold materials currently being studied, among which artificial ligament products such as Leeds Keio and LARS (Ligament Advanced Reinforcement System) are still in use in some countries. Other materials have not been promoted in clinical practice due to immature technology and other issues. The pores and porosity of artificial tendon scaffold materials also show different trends due to their different materials and preparation techniques.
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    Preparation methods, advantages, and disadvantages of cartilage scaffold materials
    Wang Zewen, Li Chenzhi, Liu Jiahe, Li Yancheng, Wu Mingjian, Cui Yan, Li Zhenhao, Xiong Wanqi, He Ting, Liu Baoyi, Yang Fan
    2024, 28 (15):  2404-2409.  doi: 10.12307/2024.378
    Abstract ( 428 )   PDF (826KB) ( 154 )   Save
    BACKGROUND: Scaffold materials serve as platforms that provide space and structure, playing a crucial role in the regeneration of cartilage tissue. Scholars from around the world are exploring different approaches to fabricate more ideal scaffold materials.
    OBJECTIVE: To review the design principles and preparation methods of cartilage scaffolds, and to further explore the advantages and limitations of various preparation methods. 
    METHODS: Literature searches were conducted on the databases of CNKI, WanFang Data, PubMed, and FMRS from 1998 to 2023. The search terms were “cartilage repair, cartilage tissue engineering, cartilage scaffold materials, preparation” in Chinese and English. A total of 57 articles were ultimately reviewed.
    RESULTS AND CONCLUSION: (1) The articular cartilage has a unique structure and limited self-repair capacity after injury. Even if self-repair occurs, the newly formed cartilage is typically fibrocartilage, which is far inferior to normal articular cartilage in terms of structure and mechanical properties. It is difficult to maintain normal function and often leads to degenerative changes. Currently, the design and fabrication of scaffold materials for cartilage repair need to consider the following aspects: biocompatibility and biodegradability, suitable pore structure and porosity, appropriate mechanical properties, and bioactivity. (2) Research on the preparation of cartilage scaffolds has made significant progress, continuously introducing new preparation methods and optimization strategies. These methods have their advantages and disadvantages, providing more possibilities for customized preparation and functional design of cartilage scaffolds according to specific requirements. 
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    Advantages and features of nanocomposite hydrogel in treatment of osteoarthritis
    Tian Linling, Guo Hairui, Du Xiaoming, Feng Jie, Zhang Xianzhe, Zhang Wenbin, Sun Haoran, Zhang Xiaobin, Wang Jingxia, Hu Yimei, Wang Yi
    2024, 28 (15):  2410-2415.  doi: 10.12307/2024.411
    Abstract ( 653 )   PDF (1264KB) ( 417 )   Save
    BACKGROUND: Nanocomposite hydrogel has great research prospects and application potential in the treatment of osteoarthritis.
    OBJECTIVE: To review the research progress of nanocomposite hydrogel in osteoarthritis and cartilage repair.
    METHODS: Databases such as CNKI and PubMed were searched. The English key words were “nanocomposite hydrogel, nanogel, osteoarthritis, cartage, physical encapsulation, electrostatic interaction, covalent crosslinking”, and the Chinese key words were “nanocomposite hydrogel, nanogel, osteoarthritis, cartage, physical encapsulation, physical encapsulation, electrostatic effect, covalent cross-linking”. After an initial screening of all articles based on inclusion and exclusion criteria, 71 articles with high correlation were retained for review.
    RESULTS AND CONCLUSION: In cell or animal experiments, nanocomposite hydrogel has the effect of improving osteoarthritis. Nanocomposite hydrogel can promote cartilage repair, improve the internal environment of osteoarthritis, and achieve the therapeutic purpose of osteoarthritis by improving the mechanical environment between joints, carrying targeted drugs, and promoting the chondrogenesis of seed cells. At present, the research of nanocomposite hydrogel in osteoarthritis disease still has a huge space to play. It is expected to open up a new way for the clinical treatment of osteoarthritis by continuing to deepen the research of material preparation and actively carrying out cell and animal experiments.
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    Biomimetic design of biomedical scaffolds and their application in tissue engineering
    Liang Chen, Zhu Tonghe, Zhu Yiyao, Li Ruizhi
    2024, 28 (15):  2416-2422.  doi: 10.12307/2024.387
    Abstract ( 481 )   PDF (1688KB) ( 389 )   Save
    BACKGROUND: Biomimetic design of bioactive materials to restore, maintain or improve the function of tissue based on the understanding of anatomy on the function and structure of biological tissue is a research hotspot in the field of regenerative medicine at present.
    OBJECTIVE: To discuss the effect of mechanical properties, three-dimensional spatial structure, and biochemical activity of biomedical scaffolds on cell behavior and review the application of biomedical scaffolds in the field of tissue engineering. 
    METHODS: The articles published in CNKI, Wanfang, Web of Science, and PubMed databases from January 2003 to April 2023 were searched by computer. The Chinese search terms were “extracellular matrix, tissue engineering, scaffolds, biomaterials, biomimetic structures, mechanical properties, three-dimensional structures, tendon-bone interface, osteochondral, neural conduits, artificial blood vessels”. English search terms were “extracellular matrix, tissue engineering, scaffolds, biomimetic structures, biomaterials, tendon bone interfaces, osteochondral, neural conduits, artificial blood vessels”. 
    RESULTS AND CONCLUSION: Cells are in a complex and dynamic three-dimensional environment, so the extracellular matrix is the ultimate target of biomaterial simulation. The bionic structure of biomedical scaffolders needs to be similar to the real microenvironment, so that cells can stick to the wall, grow and migrate normally, and maintain their diverse physiological functions. Biomimetic design of extracellular matrix in terms of mechanical properties, three-dimensional spatial structure, and biochemical properties of biomedical scaffolds can play a decisive role in tissue repair, thus affecting the final result of tissue repair. Biomimetic biomedical scaffolds have been widely used in tendon-bone interface, bone cartilage interface, nerve, vascular regeneration, and other fields, providing a promising new idea in clinical practice.
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    Research and application of carbon nanomaterials in peripheral nerve regeneration
    Zhai Yunhao, Qian Yun
    2024, 28 (15):  2423-2429.  doi: 10.12307/2024.405
    Abstract ( 410 )   PDF (1543KB) ( 504 )   Save
    BACKGROUND: Although nerve conduits provide an effective treatment approach for nerve repair, traditional nerve conduits merely serve as mechanical channels in the repair process. The therapeutic effect still needs to be improved. Carbon nanomaterials have good physicochemical properties and hold great potential in fields such as electrochemistry and tissue engineering. Nerve conduits loaded with carbon nanomaterials, after appropriate functional modifications, are expected to further enhance the quality of nerve repair.
    OBJECTIVE: To review the recent research progress of carbon nanomaterial-loaded nerve conduits/scaffolds for peripheral nerve repair.
    METHODS: PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched for the literature on the application of carbon nanomaterial catheters in peripheral nerve regeneration. English keywords were “carbon nanomaterials, carbon-based nanomaterials, nerve conduit, nerve guidance conduit, scaffold, nerve regeneration, peripheral nerve repair, peripheral nerve injury” and Chinese keywords were “carbon nanomaterials, carbon materials, graphene, carbon nanotubes, nerve conduits, nerve scaffolds, nerve repair, nerve regeneration, peripheral nerve injury”. Finally, 69 articles were selected for this review.
    RESULTS AND CONCLUSION: (1) Carbon nanomaterials primarily restore damaged neural bioelectric signal conduction by activating calcium ion channels and inducing intracellular calcium activity. The application of various nerve conduit design strategies has improved the effectiveness of nerve repair. (2) Successful intraneural vascularization is the prerequisite for repairing peripheral nerve injuries. Reactive oxygen species and reactive nitrogen species generated by carbon nanomaterials trigger subsequent signaling pathways that promote intraneural vascularization. (3) The ratio of M1 to M2 macrophages affects the repair of peripheral nerve injuries. Carbon nanomaterials promote the polarization of macrophages into the M2 phenotype, thereby exerting their anti-inflammatory and regenerative effects. (4) Some carbon nanomaterials may induce excessive generation of reactive oxygen species intracellularly, potentially exhibiting cytotoxicity detrimental to nerve repair. However, appropriate functional modifications can improve the adverse effects caused by carbon nanomaterials. (5) Although carbon nanomaterials can restore the microenvironment of peripheral nerve injuries and play a positive role in promoting peripheral nerve regeneration, their inherent cytotoxicity and unclear in vivo degradation pathways still pose challenges for clinical application. However, by employing methods such as functional modification, it is possible to enhance the biocompatibility of carbon nanomaterials. Modified carbon nanomaterials have promising prospects in the field of neural tissue engineering.
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    Preparation, characterization, and application of acylated collagen with anhydride
    Li Weizhao, Zhou Hui, Peng Xinsheng, Li Baohong
    2024, 28 (15):  2430-2436.  doi: 10.12307/2024.408
    Abstract ( 591 )   PDF (1312KB) ( 512 )   Save
    BACKGROUND: Collagen is a biomedical material with good biocompatibility, low toxicity, low immunoactivity, and high cellular affinity. However, the defects such as hydrophilicity and poor thermal stability are the key technical problems that need to be solved urgently in biomedical, tissue engineering, and other applications. 
    OBJECTIVE: To elaborate on the preparation method, characterization, and application progress of acylated collagen.
    METHODS: PubMed, X-mol, and CNKI databases were used to search the literature on acylated collagen preparation methods, characterization, and application. The search time was from January 1992 to May 2023. The English search terms were “acylated collagen, modified collagen, water-soluble collagen, acetic anhydride”. Chinese search terms were “acylated collagen, modified collagen, water-soluble collagen”. After an initial screening of all articles according to inclusion and exclusion criteria, 53 articles with high relevance were retained for review.
    RESULTS AND CONCLUSION: (1) The preparation of acylated collagen is mainly obtained by the acylation reaction of acid anhydride, and the reaction sites are mainly ε-amino and N-terminus-amino of collagen, and the reaction environment of acylation reaction needs to be carried out in an alkaline environment. (2) Succinic anhydride is the preferred reactant of acylated collagen. Carbonic anhydride, citric anhydride, and bifunctional modifiers with acylation ability have been excavated in recent years to meet various requirements, but it is still limited to laboratory preparation; complex preparation process is difficult to industrialize, and follow-up research is needed to continuously improve. (3) The characterization methods of acylated collagen are similar to those of collagen, but there is still a lack of standards for the water-soluble characterization of acylated collagen. (4) In recent years, acylated collagen has been gradually used in the preparation of lenses, hydrogels, and dressings, as well as cosmetic raw materials. However, there is still little research on the application of acylated collagen, and there is a lack of complete in vivo experiments to verify the practicality of acylated collagen.
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    Application of scaffold-based and scaffold-free strategy for treatment of growth plate cartilage regeneration
    Guo Ruoyi, Zhuang Hanjie, Chen Xiuning, Ben Yulong, Fan Minjie, Wang Yiwei, Zheng Pengfei
    2024, 28 (15):  2437-2444.  doi: 10.12307/2024.268
    Abstract ( 338 )   PDF (1186KB) ( 520 )   Save
    BACKGROUND: Tissue engineering is considered an ideal treatment for growth plate regeneration. However, most of the current research on regenerative tissue engineering is the traditional scaffold-based strategy. As the limitations of traditional scaffolds are gradually revealed, the research direction is gradually diversifying.
    OBJECTIVE: To summarize the application of scaffold-based and scaffold-free strategies in the treatment of growth plate cartilage regeneration and their respective advantages and disadvantages.
    METHODS: The relevant articles were searched from PubMed, Wiley, and Elsevier. The search terms were “growth plate injury, regeneration, tissue engineering, scaffold, scaffold-free, biomimetic, cartilage” in English. The time was limited from 1990 to 2023. Finally, 104 articles were included for review.
    RESULTS AND CONCLUSION: The biomimetic strategy is to reduce the cell composition, biological signals and unique mechanical properties of each region to the greatest extent by simulating the unique organizational structure of the growth plate, so as to build a biomimetic microenvironment that can promote tissue regeneration. Therefore, the design of a biomimetic scaffold is to simulate the original growth plate as far as possible in terms of composition, structure and mechanical properties. Although some results have been achieved, there is still the problem of the unstable regeneration effect. The scaffold-free strategy believes that the limitations of scaffolds will have adverse effects on regenerative therapy. Therefore, the design of scaffold-free constructs relies as much as possible on the ability of cells to generate and maintain extracellular matrix without interfering with cell-cell signals or introducing exogenous substances. However, there are some problems, such as poor stability, low mechanical strength and greater difficulty in operation. Biomimetic strategy and scaffold-free strategy have different emphases, advantages and disadvantages, but they both have positive effects on growth plate cartilage regeneration. Therefore, subsequent studies, whether adopting a biomimetic strategy or a scaffold-free strategy, will focus on the continuous optimization of existing technologies in order to achieve effective growth plate cartilage regeneration therapy. 
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    Cerium and cerium-based materials in dental applications
    Zhang Binjing, Wang Jian
    2024, 28 (15):  2445-2451.  doi: 10.12307/2024.246
    Abstract ( 617 )   PDF (1187KB) ( 359 )   Save
    BACKGROUND: Cerium (Ce) is the most abundant element among lanthanides, which is mostly in the form of ceria. The reversible transformation between Ce3+ and Ce4+ ions contributes to the high redox activity of cerium. Because of its antibacterial, anti-inflammatory, osteogenic, angiogenic and anti-tumor properties, cerium has been widely used in stomatology. 
    OBJECTIVE: To summarize the antibacterial, anti-inflammatory, osteogenic, angiogenic and anti-tumor mechanism of cerium, and to review the research status and application prospects of cerium and cerium-based materials in the modification of oral materials and the diagnosis and treatment of oral diseases in recent years. 
    METHODS: The articles published from database inception to 2023 were retrieved from Web of Science, PubMed, CNKI and WanFang databases with the search terms “cerium, ceria, prosthodontics, prosthesis, restorative dentistry, denture, dental implant, caries, endodontics, pulpitis, periodontitis, periodontal diseases, oral cancer” in English and “cerium, ceria, prosthodontics, implant, dental caries, dental pulp, periodontitis, periodontal disease, oral cancer” in Chinese. By analyzing and reading literature for screening, according to the inclusion and exclusion criteria, 73 articles were finally included in this review.
    RESULTS AND CONCLUSION: (1) Cerium exerts an antibacterial effect through direct contact with bacteria, oxidative stress and destroying bacterial biofilm, and exerts an anti-inflammatory function based on mimetic enzyme activity. The osteogenic and angiogenic activities of cerium involve a series of signaling pathways including ERK and Wnt signaling pathways. (2) Antibacterial, anti-inflammatory, osteogenic, and angiogenic activities allow cerium significant potential in the treatment of oral infectious diseases and regeneration of oral soft and hard tissues. However, there is still a certain gap in the application of cerium’s anti-tumor properties in the oral field. (3) Due to excellent mechanical properties and a low light-transmitting property, ceria-stabilized zirconia as a dental ceramic material can be used for core ceramics, the frameworks of dental prostheses and dental implants. (4) Benefited from its biological properties, cerium-based materials have the ability to promote osseointegration and soft tissue integration, inhibit demineralization and cariogenic bacteria, facilitate regeneration of the dentin-pulp complex, lessen inflammatory response and enhance periodontal tissue regeneration. There are wide applications of cerium in surface modifications of implants and treatments of caries, pulpitis, periodontitis and oral cancers. (5) Cerium shows certain toxicity under conditions of high concentration and long-term administration. To further expand clinical applications of cerium in dentistry, biosafety and optimization of cerium-based materials need to be further explored in the future.
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    Influence of bone microenvironment on regeneration process of tissue-engineered bone
    Zhong Siyang, Liao Qing, Zhou Xingyu, Li Xianying, Wei Jingjing, Yang Lin
    2024, 28 (15):  2452-2460.  doi: 10.12307/2024.255
    Abstract ( 490 )   PDF (1045KB) ( 159 )   Save
    BACKGROUND: Bone tissue defects are one of the most common diseases in orthopedics, and the current treatments for this disease are inadequate. The development of tissue engineering brings new hope for bone defect repair: by regulating the release of bioactive substances and the process of vascularization and neurogenesis at the defect site, it can effectively improve the microenvironment of bone tissue and promote osseointegration, which is the most promising research idea for large-size bone defect repair.
    OBJECTIVE: To explore the research progress of regulating bone microenvironment changes in bone defect repair in recent years from the effects of bioactive substances, vascularization and neurotization on three aspects of bone microenvironment changes, and to provide new ideas and strategies for the treatment of large-size bone defects. 
    METHODS: The search terms “bone tissue engineering, angiogenesis, neurotization, cytokines, bone morphogenetic protein, vascular endothelial growth factor, neuropeptides, bone microenvironment” in Chinese and English were used to search for articles on the influence of changes in the bone microenvironment and their application in bone tissue engineering published from January 1, 2001 to December 31, 2022 on CNKI, WanFang, Web of Science, Science Direct, and PubMed. Finally, 109 articles were included for review. 
    RESULTS AND CONCLUSION: (1) The bone microenvironment is essential for the induction of bone tissue stem cell growth and differentiation, and mainly consists of the extracellular matrix of the bone tissue seeds and the biochemical factors required for intercellular interactions, the local blood circulation network and the surrounding nerve tissue. (2) Bone defect repair is a continuous process divided into multiple phases that overlap and are mediated by multiple cytokines, and the same cytokine can have mutually synergistic or antagonistic effects in one or more healing phases. (3) Neovascular regeneration is key to initiating bone repair, as neovascularisation not only provides essential nutrients, osteoblasts and growth factors for bone repair, but is also a gateway for repair cells to enter the injury zone. (4) In addition to regulating the type, dose and timeliness of vascular-inducing factor release to achieve blood transport reconstruction. The study of differential release delivery systems of multiple factors and the application of gene transfer technology will be the future research direction to solve large bone defects. (5) Neuropeptides can bind to relevant receptors and act on specific signaling pathways to guide vascular growth and influence bone healing, bone regeneration and the balance between osteogenesis and osteolysis through a variety of pathways. (6) In the establishment of neuralized tissue-engineered bone, the role of changes in the bone tissue microenvironment and neuromodulation is bidirectional. Cytokines in the bone matrix can participate in neuronal signaling pathways through the blood-nerve barrier. Neuropeptides secreted by glial cells act on the bone microenvironment, affecting bone healing, bone regeneration and the balance between osteogenesis and osteolysis. (7) There are still many questions regarding the regulation of the bone microenvironment by bioactive substances and the processes of vascularization and neurogenesis, such as the rapid diffusion and degradation of cytokines in the body and their loss of activity, the temporal and spatial distribution of angiogenesis-related growth factors, and the establishment of neurogenesis through the body’s feedback regulatory mechanism, which need to be improved by subsequent studies.
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