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08 October 2022, Volume 26 Issue 28 Previous Issue   

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Design and optimization of artificial femoral unit cell structure based on response surface methodology Lian Tingting, Chen Xuewen, Zhang Bo, Wang Guangxin, Akiyoshi Osaka 2022, 26 (28):  4429-4434.  doi: 10.12307/2022.293 Abstract ( 346 )   PDF (25924KB) ( 31 )   Save BACKGROUND: Artificial bone implantation is an important method for the treatment of severe osteoporosis and bone injury. However, the mechanical compatibility with the host bone should be considered during the implantation, especially to match the Young’s modulus of the artificial bone with the host bone.  OBJECTIVE: To analyze the influence of the structure type, pillar size and aperture size on Young’s modulus and porosity of cell structure. METHODS: Three types of unit cell structures (pillar, perforated plate, cylindrical aperture) that described the microstructure of bones were designed. Orthogonal experiments were designed. The unit cell structure was statically analyzed based on finite element simulation. The range analysis and variance analysis were used to study the influence of three types of unit cell structure, pillar size and aperture size on the Young’s modulus and porosity of the unit cell structure. Based on the orthogonal experimental data, a response surface approximate model was established. The Young’s modulus of the cancellous bone of the proximal femur was taken as the optimization target. The sequential quadratic programming method was selected to optimize the parameter design of the unit cell structure. RESULTS AND CONCLUSION: The results of range analysis and variance analysis showed that the primary and secondary order of the above three factors affecting Young’s modulus was: pillar size > aperture size > structure type, and the primary and secondary order affecting porosity was: pillar size > structure type > aperture size. In addition, the response surface method was used to establish the approximate model, and the sequence quadratic programming method was adopted to optimize the unit cell structure with the Young’s modulus of femur 0.97 GPa as the optimization objective, and then the simulation verification was carried out. The results show that the optimal design method is effective, which provides a new design method for artificial bone structure. Figures and Tables | References | Related Articles | Metrics

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Biomechanical effects of cement filling location on osteoporotic vertebral compression fracture: a three-dimensional finite element analysis Ye Linqiang, Lu Guoliang, Jiang Xiaobing, Li Zhen, Weng Rui, Liang De, Huang Xuecheng, Feng Yonghong 2022, 26 (28):  4435-4440.  doi: 10.12307/2022.294 Abstract ( 513 )   PDF (1034KB) ( 60 )   Save BACKGROUND: When bipedicular percutaneous vertebral augmentation is performed for osteoporotic vertebral compression fractures, three types of cement filling location in the vertebral body are commonly seen, including anterolateral, anteromedial, and posterolateral, especially in lumbar spine with big volume of vertebral bodies. At present, no relevant biomechanical research has been found to compare the impact of these three bone cement filling locations on the biomechanical properties of fractured vertebral bodies. OBJECTIVE: To analyze and compare biomechanical effects of three types of cement filling location on osteoporotic vertebral compression fracture using three-dimensional finite element analysis method. METHODS: Osteoporotic L1-L5 three-dimensional finite element model was constructed and osteoporotic vertebral compression fractures model was simulated in L3. Three types of cement filling location, including anterolateral, anteromedial, and posterolateral, were simulated in osteoporotic vertebral compression fractures model, respectively. Four models were got for the test eventually. Maximum von Mises stress of L3 veretebral body and maximum displacement of L3 fractured area were calculated for the four models under the same loading conditions, including flexion, extension, lateral bending, and rotations. RESULTS AND CONCLUSION: (1) Under flexion, maximum von Mises stress of L3 veretebral body in anterolateral, anteromedial, and posterolateral sites was about 18.31%, 19.43%, and 28.31% of that in osteoporotic vertebral compression fractures model, respectively. Maximum displacement of L3 fractured area was about 13.92%, 16.49%, and 29.90% of that in osteoporotic vertebral compression fractures model, respectively. Therefore, compared with percutaneous vertebral augmentation pre-operation, maximum von Mises stress and maximum displacement were decreased significantly after percutaneous vertebral augmentation, with those in anterolateral site being decreased the most significantly. Similar changes could be seen in extension, lateral bending, and rotations loading conditions. (2) The results showed that anterolateral cement filling could better restore strength and stability of fractured vertebral body. To make cement fill in the anterolateral fractured area first using precise puncture and cement injection technique is suggested.  Figures and Tables | References | Related Articles | Metrics

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Naringin-chitosan/hydroxyapatite composite scaffold in repair of rat skull defect Lu Yunan, Zhang Xinzhao, Lin Binbin, Xu Gan, Chen Jingdi, Chen Shunyou 2022, 26 (28):  4441-4445.  doi: 10.12307/2022.295 Abstract ( 476 )   PDF (1167KB) ( 67 )   Save BACKGROUND: Naringin, the active ingredient of Rhizoma Drynariae, has the traditional effect of strengthening the liver and kidney and strengthening the bones and muscles, increasing the thickness of the callus and improving the quality of fracture healing. OBJECTIVE: To explore the bone conduction and bone induction properties of naringin-chitosan/hydroxyapatite composite scaffolds.   METHODS: The hydroxyapatite precursor solution with a certain calcium to phosphorus ratio and the chitosan solution containing naringin were crystallized in situ under alkaline conditions and freeze-dried to obtain a naringin-chitosan/hydroxyapatite porous scaffold. A total of 15 SD rats were randomly divided into blank group (n=5), control group (n=5) and experimental group (n=5). The 5 mm-diameter skull bone defect models were established by drilling holes. Biomaterials were not filled in the blank group. Chitosan/hydroxyapatite scaffolds were filled in the control group; and naringin-chitosan/hydroxyapatite scaffolds were filled in the experimental group. At 4 weeks after surgery, CT scans were performed to observe the skull repair. Hematoxylin-eosin staining was used to observe morphological differences. Immunohistochemical staining of bone morphogenetic protein 2 and vascular endothelial growth factor was performed to observe the expression of local osteogenic active factors in the defect areas.  RESULTS AND CONCLUSION: (1) CT scan showed that no obvious osteogenesis was seen in the skull of rats in the blank group; only a small amount of new bone was seen at the edge of the defect. In the control group, new bone formation could be seen in the defect pores, and there was less new bone. In the experimental group, the bone defect was well repaired; the density of new bone tissue and the skull around the defect pores were similar, and a large area of new bone widely filled the defect pores. (2) Hematoxylin-eosin staining showed that the defect area in the blank group was filled with thin loose reticular fibrous tissue, and a large number of inflammatory response lesions were seen, and only a small amount of new bone was formed at the edge of the defect. In the control group and the experimental group, residual scaffold material, new bone trabecula and osteoblasts were seen in the defect area; osteoblasts were distributed in clusters in the pores of the scaffold and the edges of the defect area, surrounded by a large number of capillaries. Among them, the experimental group showed a stronger ability of new bone growth. (3) Immunohistochemical staining showed that the expression levels of local osteogenic activity factors bone morphogenetic protein 2 and vascular endothelial growth factor in the experimental group were higher than those in the control and blank groups (P < 0.05). (4) The results conclude that naringin-chitosan/hydroxyapatite composite scaffolds can provide necessary carrier for bone defect repair. Naringin can create local osteogenic microenvironment, accelerate the growth and mineralization of new bone tissue, and have good bone repair performance. Figures and Tables | References | Related Articles | Metrics

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Electroactive membrane promotes bone formation in rats in vivo He Yiheng, Cheng Mingwei, Zhu Peijun, Xu Yan, Chen Jiahao, Lai Chunhua, Xu Shulan 2022, 26 (28):  4446-4451.  doi: 10.12307/2022.296 Abstract ( 546 )   PDF (1280KB) ( 46 )   Save BACKGROUND: The previous research of our group found that polarized poly(vinylidenefluoride-trifluoroethylene) has the effect on regulating the proliferation and differentiation of osteoblasts in vitro, but the role of polarized poly(vinylidenefluoride-trifluoroethylene) membrane in promoting bone defect healing in vivo is not clear.  OBJECTIVE: To establish a rat model of critical bone defect in mandible and evaluate the effect of polarized poly(vinylidenefluoride-trifluoroethylene) in promoting the healing of bone defect in vivo. METHODS: The poly(vinylidenefluoride-trifluoroethylene) membrane was prepared by flow-casting method, and after corona polarization treatment, it obtained good and stable piezoelectric properties. The physicochemical properties, electrical properties and biocompatibility of the membrane before and after polarization were characterized. Critical full-thickness bone defects with a diameter of 4 mm were prepared in eighteen Wistar rats with bilateral mandibular angles. Rats were randomly divided into three groups (n=6). Polarized poly(vinylidenefluoride-trifluoroethylene) membrane was implanted in the experimental group, and unpolarized poly(vinylidenefluoride-trifluoroethylene) membrane was implanted in the control group. The blank control group was not treated. At 4 and 8 weeks, Micro-CT scanning was used to analyze the amount of bone formation in each group, and tissue staining was used to observe the bone formation in each group. The experimental protocol was approved by the Animal Experiment Ethics Committee of Southern Medical University (approval No. 00225515). RESULTS AND CONCLUSION: (1) The surface morphology, water contact angle, elastic modulus and maximum tensile strength of poly(vinylidenefluoride-trifluoroethylene) membrane after polarization had no obvious changes. The electrical constant was -10 pc/N, and the surface potential was -83 mV. (2) The results of cell proliferation-toxicity assay showed that the polarized poly(vinylidenefluoride-trifluoroethylene) membrane promoted the proliferation of bone marrow mesenchymal stem cells, but did not produce toxic reaction to the cells. (3) At 4 and 8 weeks postoperatively, the results of Micro-CT showed that the amount of bone formation in the bone defect area of the experimental group was significantly higher than that of the control group and the blank control group (P < 0.05). (4) At 4 and 8 weeks after operation, hematoxylin-eosin staining showed that the healing speed and quality of bone tissue in the experimental group were significantly better than those in the control group and the blank control group. (5) Immunohistochemical staining at 4 and 8 weeks postoperatively showed that expression of Runx2 in the bone defect area of the experimental group was higher than that of the control group and the blank control group (P < 0.05). (6) The results showed that the polarization poly(vinylidenefluoride-trifluoroethylene) membrane had good physical and chemical properties, biocompatibility and osteogenic properties in vivo. Figures and Tables | References | Related Articles | Metrics

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Osteogenesis, angiogenesis and anti-aseptic loosening of europium-doped calcium polyphosphate bone tissue engineering scaffold Wu Yuchong, Peng Xu, Yu Xixun 2022, 26 (28):  4458-4465.  doi: 10.12307/2022.298 Abstract ( 481 )   PDF (1469KB) ( 59 )   Save BACKGROUND: The clinical success of bone grafts depends not only on osteogenesis, but also on angiogenesis, and the ability to inhibit osteoclast-mediated bone resorption. Therefore, it is particularly important to develop bio-scaffold materials with multiple functions.  OBJECTIVE: To improve various problems of traditional bone repair materials, such as low mechanical strength, poor vascular promoting ability, and insufficient osteoinductive ability through the doping of trace elements.  METHODS: A series dose of Eu (0%, 1%, 3%, 5% and 7%, molar ratio) was incorporated into calcium polyphosphate scaffolds by high temperature sintering to achieve a multifunctional europium-doped calcium polyphosphate. Infrared spectroscopy, X-ray diffraction analysis, X-ray photoelectron spectroscopy, scanning electron microscopy, mercury intrusion method and compressive strength test were used to characterize its structure, crystal form, element composition, pore size distribution, and mechanical properties. The europium-doped calcium polyphosphate scaffold was co-cultured with mouse embryonic osteoblast precursor cells and human umbilical vein endothelial cells. Biological performance was evaluated through cell proliferation detection, scanning electron microscope, laser scanning confocal microscope, and enzyme-linked immunosorbent assay.   RESULTS AND CONCLUSION: (1) The doping of Eu3+ did not change the main chain structure and crystal form of calcium polyphosphate, but it could stabilize the pore size distribution within 200-400 μm, which was conducive to bone ingrowth. (2) Compared to pure calcium polyphosphate materials, the crystal grains of europium-doped calcium polyphosphate scaffolds were bonded more closely and ranged well-ordered, which were beneficial to improve mechanical strength of materials. (3) The surface roughness of europium-doped calcium polyphosphate scaffolds was conducive to cell adhesion and spreading. Mouse embryonic osteoblast precursor cells and human umbilical vein endothelial cells seeded on europium-doped calcium polyphosphate scaffolds presented better proliferation and migration, especially 5% group. (4) The secretion of four growth factors (alkaline phosphatase and osteopontin, and human umbilical vein endothelial cells secreted vascular endothelial growth factor and matrix metalloproteinase 9) from co-cultured cells seeded on europium-doped calcium polyphosphate scaffolds was enhanced, which was conducive to the proliferation and differentiation of osteoblasts, especially 5% group. (5) 5% europium-doped calcium polyphosphate significantly up-regulated the ratio of osteoprotegerin/nuclear factor kappa B receptor activator ligand from osteoblast so that it had a potential efficacy to inhibit bone resorption, thus acted as an effect of alleviating aseptic loosening. (6) The above results show that the 5% europium-doped calcium polyphosphate scaffold has the potential to accelerate angiogenesis/osteogenesis and inhibit bone resorption, which is a promising multifunctional biomaterial.  Figures and Tables | References | Related Articles | Metrics

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Analysis of adhesion and permeability of bone scaffold with Voronoi architecture Wu Li, Huang Wei, Li Xuetao, Li Panpan, Zhang Kaihang, Shen Zhiyuan 2022, 26 (28):  4472-4476.  doi: 10.12307/2022.300 Abstract ( 505 )   PDF (1009KB) ( 74 )   Save BACKGROUND: Bone tissue engineering research results have found that the adhesion and permeability of Voronoi bone scaffold are important parameters that affect bone tissue engineering scaffolds. Good adhesiveness can ensure bone cells stick to the scaffold, and promote the bone tissue regeneration. Excellent permeability can increase the transportation of nutrients and metabolic waste in the body.   OBJECTIVE:  To study the adhesiveness and permeability of the bone scaffolds with Voronoi architecture. METHODS:  Taking Voronoi bone scaffold as the research object, its structure was modeled by Rhino software. The permeability and adhesion inside the bone scaffold were analyzed by means of computational fluid dynamics. The number of seed points was set to 20, 25, 30, and the scaling factors were 0.4, 0.5, 0.6, 0.7, 0.8, respectively, to explore the correspondence between the porosity and the permeability.  RESULTS AND CONCLUSION: (1)  The Voronoi bone scaffold structure designed by Rhino software had an average adhesion layer thickness of 0.061-0.116 mm, which had a certain adhesion capacity. Its porosity was largely determined by the scaling factor. With the continuous increase of the scaling factor, the porosity tended to rise. Within the range of the selected structural design parameters, when the scaling factor was 0.4, the porosity of the scaffold with different seed points was the smallest, which was 33.78%, 33.87%, and 33.90%, respectively. When the scaling factor was 0.8, the porosity of the scaffold structure with different seed points was the largest, which was 84.28%, 84.35%, and 84.38%, respectively. (2) The increase in the porosity had a significant impact on the permeability of the scaffold structure. With the increases of the porosity, the permeability of the bone scaffold structure rose. In the designed scaffold structure, the permeability increased from 16.98×10-8 m2 to 82.29×10-8 m2 with the increase of the porosity. (3) The relationship between the porosity of the scaffold structure and the permeability is obtained, which provides a basis for the prediction of the permeability of the bone scaffold and the analysis of the biological performance of the complex structure bone scaffold. Figures and Tables | References | Related Articles | Metrics

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Percutaneous kyphoplasty and percutaneous vertebroplasty for osteoporotic vertebral compression fractures: relationship of bone cement leakage with postoperative pain, Cobb angle of injured vertebrae, and gait recovery Li Youwen, Zheng Xingping, Zeng Jianhong, Chen Yu 2022, 26 (28):  4494-4499.  doi: 10.12307/2022.284 Abstract ( 475 )   PDF (876KB) ( 34 )   Save BACKGROUND: Percutaneous vertebroplasty and percutaneous kyphoplasty are safe and effective surgical options for the treatment of osteoporotic vertebral compression fractures. Both have their advantages and disadvantages. OBJECTIVE: To explore the effect of percutaneous kyphoplasty and vertebroplasty on the early and mid-term gait of patients with osteoporotic vertebral compression fractures. METHODS: A total of 115 patients with osteoporotic vertebral compression fractures who were admitted to the Department of Spine Surgery, People’s Hospital of Dongxing District in Neijiang City from March 2018 to July 2020 were divided into two groups using a random number table. Percutaneous kyphoplasty bone cement injection treatment was conducted in 63 cases and percutaneous vertebroplasty bone cement injection treatment was performed in 52 cases. The amount of bone cement in the fractured vertebrae and the leakage of bone cement were recorded during the operation. X-ray examinations were performed before and 12 weeks after the operation. Cobb angle of the injured vertebrae was measured. The two groups of patients were tested for gait and pain assessment before, 6, and 12 weeks after the operation. Visual analogue scale score was used for pain assessment. The study was approved by the Research Ethics Committee of the People’s Hospital of Dongxing District, Neijiang City.  RESULTS AND CONCLUSION: (1) The amount of bone cement in the kyphoplasty group was more than that in the vertebroplasty group (P < 0.05), and the leakage rate of bone cement was lower than that in the vertebroplasty group (12.7%, 28.8%, P < 0.05). (2) In comparison with preoperative data, the Cobb angle of the injured vertebrae in the kyphoplasty group decreased at 12 weeks (P < 0.05), but there was no significant change in the vertebroplasty group  (P > 0.05). The Cobb angle of the injured vertebrae in the kyphoplasty group was lower than that of the vertebroplasty group (P < 0.05). (3) The postoperative pain and walking movement function of the two groups were significantly improved, and the pain condition and walking movement function of the kyphoplasty group were better than those of the vertebroplasty group at 6 weeks after surgery (P < 0.05). There was no significant difference in pain condition and walking movement function between the two groups at 12 weeks after surgery (P > 0.05). (4) At 12 weeks postoperatively, there was no significant difference in postoperative pain, Cobb angle and gait parameters between the cement leakage group and the non-cement leakage group (P > 0.05). (5) The results have shown that compared with percutaneous vertebroplasty, percutaneous kyphoplasty can restore the walking movement function of patients with osteoporotic vertebral compression fractures earlier, with better fracture reduction and analgesic effects, less bone cement leakage. Figures and Tables | References | Related Articles | Metrics

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Risk factors of recurrent fracture after injection of calcium phosphate cement in kyphoplasty: advanced age and stress change Li Yang, Du Yibin, Liu Yiming, Li Fanjie 2022, 26 (28):  4507-4513.  doi: 10.12307/2022.306 Abstract ( 345 )   PDF (840KB) ( 34 )   Save BACKGROUND: At present, the possible risk factors and pathogenesis of the recurrent vertebral fractures after injection of calcium phosphate cement in percutaneous kyphoplasty are still controversial. The main points are related to the clinical characteristics of patients and surgical related factors. OBJECTIVE: To investigate the risk factors of the recurrent fractures in patients with osteoporotic vertebral compression fracture after injection of calcium phosphate cement in percutaneous kyphoplasty.  METHODS: The clinical data of 162 patients (191 vertebrae) with osteoporotic vertebral compression fractures admitted to the Third Affiliated Hospital of Anhui Medical University from February 2016 to February 2018 were retrospectively analyzed. All patients, aged 51-88 years, were treated with kyphoplasty and injection of calcium phosphate cement. All patients were followed up for more than 2 years. There were 34 cases (44 vertebrae) with refracture after operation, and 128 cases (147 vertebrae) without refracture as control group. The age, sex ratio, bone cement injection volume, unilateral or bilateral puncture, symmetrical distribution of bone cement across the midline, leakage of bone cement, contact of bone cement with upper and lower endplates, number of fractured vertebral bodies before operation, distribution of fractured vertebral bodies before operation, compression degree of fracture before operation, taking anti-osteoporosis drugs after operation, bone mineral density before operation and old vertebral fractures before operation, Cobb angle change after operation and recovery rate of anterior edge height after operation were compared between the two groups. Univariate independent sample t-test and multivariate logistic regression analysis were performed. RESULTS AND CONCLUSION: (1) There were significant differences between the two groups in age, symmetrical distribution of bone cement across the midline and distribution of bone cement on endplate (P < 0.05), but there were no significant differences in other indexes (P > 0.05). (2) Multivariate logistic regression analysis showed that age (P=0.006, OR=1.086), bone cement contact with the upper and lower endplates (P=0.025, OR=2.516) and bone cement in the vertebral body without midline symmetry (P=0.012, OR=0.344) were independent risk factors for recurrent vertebral fractures. (3) The results showed that the elderly status of patients with osteoporotic vertebral compression fractures, bone cement contacting the upper and lower endplates at the same time and not crossing the midline symmetry were independent risk factors for the new fracture after percutaneous kyphoplasty. The different distribution of bone cement in the vertebrae affected the new fracture by changing the internal stress of the vertebrae and the spinal line of force. Figures and Tables | References | Related Articles | Metrics

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Percutaneous vertebroplasty in treatment of osteoporotic vertebral compression fracture by two different approaches: bone cement leakage and safety Xue Guang, Yang Xinming, Zhang Ying 2022, 26 (28):  4514-4518.  doi: 10.12307/2022.307 Abstract ( 338 )   PDF (706KB) ( 102 )   Save BACKGROUND: Clinical therapies of osteoporotic vertebral compression fracture have two different approaches, including unilateral pedicle extrapedicle and bilateral pedicle approach of percutaneous vertebroplasty, but there were fewer reports about postoperative bone cement leakage rate and security in the two approaches. OBJECTIVE: To compare postoperative bone cement leakage rate and security with osteoporotic vertebral compression fracture by two different approaches, unilateral pedicle extrapedicle and bilateral pedicle approach of percutaneous vertebroplasty.   METHODS: This study enrolled 60 cases with the osteoporotic vertebral compression fracture who were patients meeting the inclusion criteria in the First Affiliated Hospital of Hebei North University from January 2018 to December 2020. The 60 cases were randomly divided into two groups according to surgical approach. Group A (n=30) was treated with unilateral pedicle extrapedicle approach of percutaneous vertebroplasty. Group B (n=30) was treated with bilateral pedicle approach of percutaneous vertebroplasty. The volume of bone cement injection, bone cement leakage rate and other complications, as well as kyphosis angle of the compressive vertebral body, the visual analogue scale score, and Oswestry disability index were compared between the two groups. RESULTS AND CONCLUSION: (1) There was no statistical significance in the volume and leakage rate of bone cement injection in two groups (P > 0.05). (2) Visual analogue scale score and Oswestry disability index were significantly lower at 1, 3 days, and 1 month after surgery compared with that preoperatively in both groups (P < 0.05). Postoperative kyphosis angle of the compressive vertebral body was less than that preoperatively (P < 0.05). There was no statistical difference in visual analogue scale score, Oswestry disability index, and kyphosis angle at various time points after surgery in both groups (P > 0.05). (3) The results suggest that satisfactory clinical effect can be obtained by two different approaches, unilateral pedicle extrapedicle and bilateral pedicle approach of percutaneous vertebroplasty. Figures and Tables | References | Related Articles | Metrics

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Gelatin-alginate composite microspheres and gels for cartilage damage repair Jiang Haoran, Gao Jianming, Lin Wancheng, Li Ting, Li Huo, Wang Peng, Feng Jing, Meng Haoye, Peng Jiang, Ding Lixiang 2022, 26 (28):  4452-4457.  doi: 10.12307/2022.297 Abstract ( 585 )   Save BACKGROUND: Minimally invasive treatment of cartilage injury is highly demanding for microcarriers, which need to have high cytocompatibility, strong cell adhesion, better mechanical properties with low immunogenicity. Simultaneously, the clinical use conditions are more demanding compared to the laboratory, and liquid microcarriers are significantly better than solid microcarriers when they are used minimally invasively or for injection. OBJECTIVE: To prepare a brand-new polymer organic microcarrier for repairing cartilage. METHODS: Gelatin microspheres at a concentration of 6% were prepared by chemical emulsification of gelatin mixed and stirred with liquid paraffin (w/O), fixed by lyophilization followed by absolute ethanol treatment, then fixed using ultraviolet cross-linking. The microsphere morphology was observed by electron microscopy. The gelatin-alginate composite gel was prepared by dispensing the gel with sodium alginate at a concentration of 7% and incubating with gelatin microspheres for 2 hours. Cell-containing gelatin-alginate composite microspheres were prepared by dropping adipose mesenchymal stem cell suspension into gelatin-alginate composite gel and incubating for 24 hours, and fully crosslinking by dropping into 5% CaCl2 solution. The cytotoxicity of the extracts from cell-free gelatin-alginate composite microspheres was examined by CCK-8 assay. The cytocompatibility of cell-containing gelatin-alginate composite microspheres was observed by using live & dead staining. Approximately 1 mL of gelatin-alginate composite gel was aspirated into a 10 mL needle tube for injection, and the gel not injected versus injected 1 and 3 times was observed by light microscopy. RESULTS AND CONCLUSION: (1) As observed by scanning electron microscope, the pores of gelatin microspheres were relatively uniform and the surface was hierarchical, and most of the particles were distributed between 180 and 500 μm in size. (2) As indicated by the live & dead staining, the cells in gelatin-alginate composite microspheres containing cells grew well and carried a large number and even distribution of cells at 24 hours of culture, and the cell viability was above 90% after 1, 3, and 7 days of culture. (3) CCK-8 assays showed no significant cytotoxicity of extracts from cell-free gelatin-alginate composite microspheres. (4) The morphology of the gelatin microspheres in the gelatin-alginate composite gel was unchanged after 1 and 3 injections compared with that when it was not injected, indicating good mechanical properties of the gelatin-alginate composite gel. (5) The results indicated that the combined use of cell-containing gelatin-alginate composite microspheres and cell-containing gelatin-alginate composite gels could make the gels play the role of tissue glue, which is beneficial for materials to adhere closely to the target area. Figures and Tables | References | Related Articles | Metrics

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Chitosan/alginate composite scaffold combined with hawthorn leaf flavonoids for spinal cord injury repair Liu Ming, Wang Kai 2022, 26 (28):  4466-4471.  doi: 10.12307/2022.299 Abstract ( 410 )   PDF (1013KB) ( 32 )   Save BACKGROUND: Studies have shown that hawthorn leaf total flavonoids have a certain therapeutic effect on spinal cord injury, but the method of administration is limited to intraperitoneal injection, and there are rare reports of direct application to the site of spinal cord injury.   OBJECTIVE: To compare the effects of chitosan alginate composite scaffold loaded with hawthorn leaf flavonoids sustained-release microspheres and intraperitoneal injection of hawthorn leaf flavonoids combined with chitosan alginate composite scaffold in the repair of spinal cord injury. METHODS:  Chitosan alginate composite scaffolds, hawthorn leaf flavonoids sustained-release microspheres and chitosan alginate composite scaffolds loaded with hawthorn leaf total flavonoids sustained-release microspheres were prepared. Forty Sprague-Dawley rats were used to establish a model of complete spinal cord injury and were randomly divided into four groups. Injury control group received intraperitoneal injection of saline after surgery. Rats in the stent group were implanted with a chitosan alginate composite stent, and injected intraperitoneally with physiological saline after the operation. Rats in the stent + drug injection group were implanted with chitosan alginate composite stent, and injected intraperitoneally with 20 mg/(kg·d) hawthorn leaf total flavonoids after surgery. Rats in the drug loaded stent group were implanted with chitosan alginate composite stent loaded with sustained-release microspheres, and injected intraperitoneally with physiological saline after the operation. BBB score and inclined plate test were used to evaluate the motor function of rats within 8 weeks after operation. The pathological morphology and western blot assay of spinal cord tissue were observed at 8 weeks after operation.   RESULTS AND CONCLUSION: (1) Since 2 weeks after operation, BBB score and inclined plate test angle of three groups of stent implantation were higher than those of injury control group (P < 0.05), and those of stent + drug injection group and drug loaded stent group were higher than those of stent group (P < 0.05), and that of drug loaded stent group was higher than that of stent + drug injection group (P < 0.05). (2) Hematoxylin-eosin staining showed that in the injury control group, no spinal cord tissue was found in the injured area, and only thin filamentous connection was found. The stent implanted in the other three groups was closely connected with the injured spinal cord end, and tissue and cells grew into the scaffold material. There were more tissues in the stent + drug injection group and drug loaded stent group. (3) Western blot assay demonstrated that the expression of glial fibrillary acidic protein in three groups of stent implantation was lower than that in injury control group (P < 0.05). The expression levels of neurofilament protein 200, myelin basic protein, and growth-associated protein 43 were higher in the three groups of stent implantation than those in the injury control group (P < 0.05). The expression of glial fibrillary acidic protein in drug loaded stent group was lower than that in stent group and stent + drug injection group (P < 0.05), and that in stent + drug injection group was lower than that in stent group (P < 0.05). The expression levels of neurofilament protein 200, myelin basic protein, and growth-associated protein 43 were higher in drug loaded stent group than that in stent group and stent + drug injection group (P < 0.05). The expression levels of neurofilament protein 200, myelin basic protein, and growth-associated protein 43 were higher in stent + drug injection group than that in stent group (P < 0.05). (4) The results have showed that intraperitoneal injection of total flavonoids from hawthorn leaves or local application of sustained-release microspheres combined with chitosan alginate composite scaffolds can promote the repair of spinal cord injury, and the effect of local application of sustained-release microspheres is better. Figures and Tables | References | Related Articles | Metrics

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Polydatin loaded collagen/heparin sulfate scaffold in the treatment of spinal cord injury in rats Liu Kang, Wang Yongping, Zuo Kebin, Yang Haitao, Jia Bin 2022, 26 (28):  4500-4506.  doi: 10.12307/2022.305 Abstract ( 454 )   PDF (1069KB) ( 59 )   Save BACKGROUND: At present, the research on the neuroprotective effect of polydatin has gradually become a hot spot in the field of neurology. The research direction is mostly focused on ischemic cerebrovascular disease, and there are few studies on the application of spinal cord injury.  OBJECTIVE: With collagen/heparin sulfate scaffold as carrier, polydatin was applied to the injured spinal cord to observe the repair effect. METHODS: (1) Collagen/heparin sulfate scaffolds and collagen/heparin sulfate scaffolds loaded with 0.5, 1, 1.5 mmol/L polydatin were prepared. The third generation of rat neural stem cells was seeded on four kinds of scaffolds, and the proliferation of cells was detected by CCK-8 assay. During inducing neural differentiation of neural stem cells, the expression levels of glial fibrillary acidic protein, Tuj-1 and Oligo were detected by immunofluorescence staining and RT-PCR. (2) The spinal cord injury model of adult male SD rats was established and divided into three groups. The model control group (n=10) was not implanted with any materials. The control group (n=10) was implanted with collagen/heparin sulfate scaffold, and the experimental group (n=10) was implanted with 1 mmol/L polydatin/collagen/heparin sulfate scaffold. Meanwhile, sham operation group (n=10) was set up. BBB score was used to test the motor function of the right hind limb within 8 weeks after operation. At 8 weeks after operation, the spinal cord tissues were taken for histological observation, immunohistochemical analysis, and western blot assay. RESULTS AND CONCLUSION: (1) At 3 and 7 days of culture, the absorbance value of cell proliferation on 1 mmol/L polydatin/collagen/heparin sulfate scaffold was higher than that on the other three scaffolds (P < 0.05). (2) Immunofluorescence staining 7 days after induction showed that the expression of glial fibrillary acidic protein in 1 and 1.5 mmol/L polydatin/collagen/heparin sulfate scaffold groups were less than those in the other two collagen/heparin sulfate scaffold groups, but the expression levels of Oligo and Tuj-1 were more than those in the other two collagen/heparin sulfate scaffold groups. (3) RT-PCR results showed that the expression of glial fibrillary acidic protein mRNA in 1 and 1.5 mmol/L polydatin/collagen/heparin sulfate scaffold groups was lower than that in the other two collagen/heparin sulfate scaffold groups (P < 0.05). There was no significant difference in the expression of Tuj-1 mRNA among the four groups. The expression of Oligo mRNA in 1 mmol/L polydatin/collagen/heparin sulfate scaffold group was higher than that in the other three groups (P < 0.05). (4) Spinal cord injury repair experiments showed that the BBB score of the experimental group was always higher than that of the model control group and the control group 2-8 weeks after operation (P < 0.05). Hematoxylin-eosin staining showed that the spinal cord defects in the control group and the observation group were filled with scaffolds, and the space between the tissues was smaller than that in the model control group. The tissue continuity and space in the observation group were better than those in the control group. Immunohistochemical analysis and western blot assay showed that the expression of neurofilament-200 protein in the experimental group was higher than that in the control group and model control group (P < 0.05). The expression of glial fibrillary acidic protein in the experimental group was lower than that in the control group and model control group (P < 0.05). (5) It is concluded that polydatin loaded collagen/heparin sulfate scaffolds can promote the repair of spinal cord injury. Figures and Tables | References | Related Articles | Metrics

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3D printed collagen/chitosan scaffolds crosslinked by genipin Zhang Jiaying, Suo Hairui, Xu Mingen, Wang Ling 2022, 26 (28):  4477-4482.  doi: 10.12307/2022.301 Abstract ( 597 )   PDF (1508KB) ( 70 )   Save BACKGROUND: Collagen/chitosan scaffolds need to be cross-linked to achieve corresponding mechanical properties. Studies have shown that the regulation of crosslinking agent concentration can control the physical and chemical properties of collagen/chitosan scaffolds.  OBJECTIVE: To explore the effect of genipin concentration on physical and chemical properties of collagen/chitosan scaffolds, and manufacture tissue engineering scaffolds with adjustable physical and chemical properties.  METHODS: Collagen and chitosan were separately dissolved in weak acid and then mixed as printing ink. The collagen/chitosa scaffolds were printed using biological 3D printer at low-temperature, then lyophilized and neutralized, and crosslinked with 1, 3 and 5 mmol/L genipin. The apparent structural stability, tensile strength, swelling performance, degradation performance and biocompatibility of scaffolds of each group were detected.  RESULTS AND CONCLUSION: (1) After the scaffold was soaked in PBS for 3 days, compared with the uncrosslinked freeze-dried scaffold, the surface of the collagen scaffold maintained regular pore structure after crosslinking, but the scaffold showed obvious deformation. The surface structure of the collagen/chitosan scaffold was regular after crosslinking. The collagen/chitosan scaffold cross-linked with only 1 mmol/L genipin had slight deformation. (2) With the increased concentration of genipin, the mechanical properties of scaffolds of each group increased, and the mechanical properties of collagen/chitosan scaffolds at the corresponding crosslinking concentration were better than those of collagen scaffolds. (3) With the increased concentration of genipin, the swelling rate of the collagen scaffold decreased, and the swelling rate of the collagen/chitosan scaffold did not remarkably change. (4) After soaking in collagenase solution, the collagen scaffolds crosslinked with different concentrations of genipin were totally degraded within 1 hour. The degradation rate of collagen/chitosan scaffold decreased with the increased concentration of genipin, showing a trend of rapid first and then smooth. (5) After inoculating bone marrow mesenchymal stem cells on the crosslinked scaffolds for 3 days, the number of cells on the 1 and 3 mmol/L genipin crosslinked collagen/chitosan scaffold (or collagen scaffold) was significantly more than that on the 5 mmol/L genipin crosslinked collagen/chitosan scaffold (P < 0.05). (6) Results have suggested that genipin can adjust the physical and chemical properties of collagen/chitosan scaffolds within a certain extent. Among them, collagen/chitosan scaffold crosslinked with 3 mmol/L genipin has good mechanical properties, resistance to enzymatic hydrolysis and biocompatibility. Figures and Tables | References | Related Articles | Metrics

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Preparation and mechanical properties of collagen type II-silk fibroin-hyaluronic acid composite scaffold Liu Gang, Gao Lilan, Shi Feifei, Wang Shixin, Luo Lailong, Li Ruixin, Zhang Chunqiu 2022, 26 (28):  4519-4524.  doi: 10.12307/2022.308 Abstract ( 434 )   PDF (798KB) ( 65 )   Save BACKGROUND: Collagen type II, silk fibroin and hyaluronic acid, which can provide an ideal microenvironment for cells, have become ideal scaffold materials for cartilage repair. OBJECTIVE: To evaluate physicochemical properties and biomechanical properties of cartilage tissue engineering scaffolds prepared from collagen type II, silk fibroin and hyaluronic acid. METHODS: Collagen type II-silk fibroin-hyaluronic acid composite scaffolds were prepared by low-temperature 3D printing technology. The microstructure, porosity and water absorption of scaffold were detected. Different strain rates were used to compress the scaffold, and the rate dependent properties of the scaffold were investigated. Constant stress level or constant strain was applied on the surface of scaffold for 3 600 s, and the creep behavior and stress relaxation behavior were investigated. RESULTS AND CONCLUSION: (1) The prepared scaffolds had three-dimensional porous structure, uniform pore size and good connectivity. The porosity was (85.1±1.6)%. The water absorption expansion rate was (1 071.7±131.6)%. (2) Under different strain rates, the compressive stress-strain curves of cartilage scaffolds did not coincide, which indicated that the compressive mechanical properties of cartilage scaffolds were rate dependent. With the increase of strain rate, the Young’s modulus increased. (3) When the stress level was constant, the creep strain first increased rapidly and then increased slowly. When the stress level increased, the creep strain also increased. (4) When the compression strain was constant, the stress of scaffold decreased rapidly at first and then slowly with the relaxation time. With the increase of the compression strain, the stress at different times increased. (5) The mechanical properties of the collagen type II-silk fibroin-hyaluronic acid composite scaffolds are similar to those of host cartilage, which means that the prepared scaffold is a kind of nonlinear viscoelastic material. Figures and Tables | References | Related Articles | Metrics

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Preparation and in vitro evaluation of injectable microspheres loaded with cells He Jiachen, Liu Chang, Chen Chichi, Shi Qin 2022, 26 (28):  4483-4488.  doi: 10.12307/2022.302 Abstract ( 580 )   PDF (2283KB) ( 203 )   Save BACKGROUND: The use of biological materials as cell carriers can provide a 3D culture microenvironment, support cell viability and function, and may expand the number and therapeutic effects of cell therapy. Therefore, it is very important to find a suitable biological material. OBJECTIVE: To prepare injectable gelatin methacryloyl porous microspheres, and explore their biocompatibility and the potential of loaded cells for tissue engineering. METHODS: Injectable gelatin methacryloyl porous microspheres were prepared by microfluidic technology. The microscopic morphology and hardness of microspheres were characterized. MC3T3-E1 cells were cultured in normal medium as control group and microsphere extract as experimental group. Cell proliferation was detected by CCK8 assay. Cell survival was detected by live dead cell staining. Microspheres were co-cultured with CD3+ T cells. CD3+ T cells cultured alone were used as controls. The effect of microspheres on T cell activation was observed under light microscope. The morphology of T cells loaded with microspheres was observed by Dapi staining. Flow cytometry was used to verify whether co-culture with microspheres influenced the ratio of CD4+ T cells to CD8+ T cells.  RESULTS AND CONCLUSION: (1) Under the inverted microscope, the microspheres were highly dispersed and uniform in size. The diameter size met the injectable condition. Under scanning electron microscope, the microspheres formed porous structure after freeze-drying, and pores were uniformly distributed. The elastic modulus of the microspheres was (9.76±2.04) kPa. (2) CCK-8 assay and live dead cell staining results demonstrated that the tendency and activity of proliferation of MC3T3-E1 cells cultured in the two media had no difference. (3) Under optical microscope, co-culture with microspheres for 2 days did not cause CD3+ T cell activation, and did not interfere with the activation of CD3+ T cells. CD3+ T cells were distributed on the surface and pores of the microspheres. (4) Flow cytometry results showed that microspheres did not affect the ratio of CD4+ T cells to CD8+ T cells. (5) An injectable gelatin methacryloyl porous microsphere was prepared by microfluidic technology, which has good biocompatibility and does not affect cell. It is a kind of biomaterial with broad application prospect in tissue engineering.  Figures and Tables | References | Related Articles | Metrics

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Preparation and in vitro release of curcumin sustained-release microspheres Li Xikai, Meng Yongchun, Fu Li, Liu Qing, Wang Xiao, Gu Chengxu, Huang Fei 2022, 26 (28):  4489-4493.  doi: 10.12307/2022.303 Abstract ( 587 )   PDF (914KB) ( 50 )   Save BACKGROUND: Curcumin can inhibit inflammation and promote axonal growth, but it has a short half-life and a fast clearance rate.   OBJECTIVE:  To prepare curcumin sustained-release microspheres to release curcumin slowly and continuously. METHODS:  Curcumin sustained-release microspheres were synthesized by O/W emulsification volatilization method using polylactic acid-glycolic acid copolymer as raw material. The preset drug loading rates were 10% and 20%, respectively, and set as No. 1 and No. 2 microspheres. The curcumin sustained release microspheres were synthesized by O/W emulsification volatilization method using L-lactic acid-polycaprolactone copolymer as raw material. The preset drug loading rates were 10% and 20%, respectively, and the microspheres were set as No. 3 and No. 4. The surface morphology of the microspheres was observed by scanning electron microscopy, and the drug loading and encapsulation efficiency of the microspheres were determined by high performance liquid chromatography. Four groups of microspheres were immersed in PBS release solution containing 1% sodium dodecyl sulfate, and the sustained release of curcumin microspheres was detected under simulated physiological environment.     RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that the particle size and morphology of No. 3 and No. 4 curcumin microspheres were better than those of No. 1 and No. 2 curcumin microspheres. (2) The encapsulation rate of No. 3 microspheres was higher than that of the other three groups (P < 0.05, P < 0.01), and there was no significant difference in the encapsulation rate of No. 1, 2 and 4 microspheres (P > 0.05). (3) The drug loading rates of No. 2, 3 and 4 microspheres were higher than that of No. 1 microsphere (P < 0.01), and the drug loading rates of No. 2 and 4 microspheres were higher than that of No. 3 microsphere (P < 0.01). (4) The in vitro release of No. 3 curcumin sustained-release microspheres lasted for 14 days, and the release of the other three kinds of microspheres lasted for 21 days. The cumulative release rate of No. 1 and No. 3 was higher than that of No. 2 and No. 4, and the curcumin release concentration of No. 3 was higher than that of No. 1. (5) The results showed that slow-release effect of the curcumin sustained-release microspheres with a preset loading rate of 10% prepared by L-lactic acid-polycaprolactone copolymer best meets the Zero order release requirements. Figures and Tables | References | Related Articles | Metrics

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Role and application of polylactic acid-hydroxyacetic acid copolymer scaffolds in bone defect repair and regeneration Lu Renpei, Zou Zhichen, Zhao Fengnian, Zheng Changming, Song Keguan 2022, 26 (28):  4525-4531.  doi: 10.12307/2022.309 Abstract ( 410 )   PDF (18866KB) ( 46 )   Save BACKGROUND: Polylactic acid-hydroxyacetic acid copolymer with good biocompatibility, plasticity, and full biodegradation becomes the ideal material of artificial bone source. However, its lack of hydrophilic, absence of osteogenesis ability, and acidification environment induced by degradation products are detrimental to bone defect repair. Thus, modification is very necessary.  OBJECTIVE: To review the research progress of polylactic acid-hydroxyacetic acid copolymer scaffolds. METHODS: The computer was used for article retrieval on CNKI and PubMed databases published from January 2000 to November 2020. The keywords were “polylactic acid-hydroxyacetic acid copolymer, PLGA, bone defect, composite scaffold, hydroxyapatite, tricalcium phosphate, modification, surface modification, blending modification” in English and Chinese, respectively. Articles with low correlation, outdated or repeated articles were excluded. RESULTS AND CONCLUSION: There are many modification methods of polylactic acid-glycolic acid copolymer scaffold, and the main modification methods are blending modification and surface modification. Blending modification can improve the mechanical properties and hydrophilicity of the scaffold by adding other substances, such as hydroxyapatite, tricalcium phosphate, magnesium hydroxide and other inorganic substances during the scaffold manufacturing, change the cell behavior, and promote osteogenesis. Surface modification is to coat the surface of the scaffold with a layer of active substances to regulate the cell-scaffold interaction. Although the performance of stents has been improved by various methods, there are still many difficulties in clinical application. Figures and Tables | References | Related Articles | Metrics

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Modification of natural and composite alginate hydrogels and repair of bone defect with composite systems Fan Yi, Liu Yadong, Cui Yutao, Liu He, Tian Yuhang, Li Shaorong, Wang Gan, Wu Dankai, Peng Chuangang 2022, 26 (28):  4532-4538.  doi: 10.12307/2022.310 Abstract ( 495 )   PDF (1027KB) ( 104 )   Save BACKGROUND: As a cell scaffold material for bone tissue engineering, alginate hydrogel has attracted attention due to its good biocompatibility and renewable characteristics. However, due to the slow degradation and instability of natural alginate hydrogel, it may not achieve the desired effect in the body environment. Therefore, modification of natural alginate hydrogel and construction of its composite system are needed to meet the needs of bone repair. OBJECTIVE: To introduce the structure and modification strategy of natural alginate hydrogel, and the construction strategy of composite alginate hydrogel. It emphasizes the various functions of alginate hydrogel and its composite system in different bone defect repair, and summarizes the current research focus and prospects the future development trend. METHODS: With “alginate hydrogel, bone defect, bone repair, alginate, bone defect, bone repair” as the key words, the author searched related articles on PubMed, Web of Science, Medline, Wanfang, CNKI and VIP databases from 1995 to 2021. Totally 69 articles were analyzed after screening. RESULTS AND CONCLUSION: (1) Through oxidation, γ-ray irradiation and other treatments, alginate hydrogel can achieve faster biodegradability, and different crosslinking methods can make it have different chemical structures. (2) Through the construction of the composite system, the alginate hydrogel and the composite system can be used as carriers for cells, bioactive factors and drugs, and can be used alone or in combination with other stents. (3) Due to the above complex properties, alginate gel and its composite system have a good prospect in the repair of bone defects, and in some existing research reports, complete bone bridging of critical bone defects has been achieved. Alginate hydrogel composite systems provide potential solutions for bone repair. Accelerated healing of bone defects and critical bone defect healing are achieved through controlled delivery of local bioactive substances. (4) In the repair of large segment and load-bearing bone defects, other scaffolds with high mechanical strength can be combined to enhance the bone integration capability of other scaffolds while providing mechanical load-bearing. These solutions can adapt to different requirements for bone defect repair. (5) To sum up, alginate gel and its composite system have shown a good effect on promoting bone tissue repair in animal experiments, providing a potential way for bone tissue engineering to repair bone defects. However, there is no systematic clinical trial at present, so more research and exploration are needed before it actually serves clinical work. Figures and Tables | References | Related Articles | Metrics

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Role and regulatory mechanism of microRNA in bone tissue repair around dental implants Yang Qiongqiong, Li Ping, Wang Qian 2022, 26 (28):  4539-4545.  doi: 10.12307/2022.311 Abstract ( 509 )   PDF (709KB) ( 45 )   Save BACKGROUND: The regulation of cell function is the key to bone formation on the surface of dental implants. Understanding bone reconstruction from the perspective of cells and molecules is helpful to improve the success rate of dental implants. Studies have found that microRNA (miRNA), as a key factor controlling cell function, plays an important role in the regulation of cell differentiation of bone tissue around dental implants.  OBJECTIVE: To review the regulation mechanism of miRNA in bone tissue repair around dental implants, the influence of dental implant surface morphology on miRNA expression, and the application of miRNA in bone tissue repair.  METHODS: Articles were searched by the first author on PubMed, Medline, and Sciencedirect databases. Search terms were “microRNA, bone remodeling, dental implants, mesenchymal stem cells, titanium, osseointegration”. Preliminary screening was performed by reading the title and abstract. After excluding the research and experiment unrelated to the topic of the article, 61 articles were finally included for result analysis. RESULTS AND CONCLUSION: (1) miRNAs participate in osteoblast differentiation by directly targeting Runx2 and Osterix genes or influencing other genes that enhance or inhibit the expression level of Runx2 and Osterix, and interacting with bone morphogenetic protein/Smads, Wnt/β-catenin signaling pathway and integrin. (2) miRNAs regulate osteogenesis-angiogenesis coupling by stimulating the expression of osteoblast marker genes. (3) Many experiments have confirmed that the surface morphology of titanium implants affects the expression of miRNA, and micro/nano structure can promote the proliferation and differentiation of osteoblasts better. The surface with nano rough morphology can improve the response of bone tissue repair by expressing miRNA related to osteogenic genes. (4) Micro-arc oxidation coating of titanium implants can promote the osteogenic differentiation of mesenchymal stem cells by activating miRNAs. It is feasible to construct genetically modified tissue engineering implants by combining miRNAS with micro-arc titanium oxide implants. Figures and Tables | References | Related Articles | Metrics

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Reducing the recurrence of infection after the application of Masquelet technique for osteomyelitis Ci Wentao, Zhang Xinlong, Yan Shi, Wang Zhao 2022, 26 (28):  4546-4552.  doi: 10.12307/2022.312 Abstract ( 467 )   PDF (753KB) ( 35 )   Save BACKGROUND: Masquelet technique is one of the effective methods for the treatment of large segmental bone defects of extremities, especially after debridement of osteomyelitis. The recurrence rate of infection after treatment of osteomyelitis is as high as 10%-15%. How to prevent and reduce infection recurrence is the key to the application of Masquelet technology in the treatment of osteomyelitis. OBJECTIVE: To explore the key points of how to reduce the recurrence of infection after the application of Masquelet technique in the treatment of osteomyelitis. METHODS: The relevant articles from January 2010 to March 2021 were searched on PubMed, CNKI and Wanfang databases, with English search term as “Masquelet technique; induced membrane technique; bone infection; osteomyelitis; soft tissue reconstruction; antibiotics; negative pressure wound therapy; debridement”; Chinese search terms were “Masquelet technology; induced membrane technique; bone infection; osteomyelitis; soft tissue reconstruction; antibiotics; negative pressure wound therapy; debridement”. The related contents of how to reduce the recurrence rate of infection after the application of Masquelet technology in the treatment of osteomyelitis were summarized. RESULTS AND CONCLUSION: The improvement of debridement technique, the optimization of the application of antibiotics, the improvement of local soft tissue reconstruction and the improvement of negative pressure wound therapy are the four main points to reduce the recurrence of infection after osteomyelitis treated by Masquelet technique. The action of targeted antibiotics loaded with antibiotic carriers on the focus of infection can effectively improve the bacteriostasis of local antibiotics. How to accurately regulate the local antibiotic release curve to cope with the change of local bacterial load at different times is the direction that scholars need to further study in the future. Reducing the effect of high antibiotic release on the biological properties of induced membrane, the combined application of antibiotic carrier technology and induced membrane technology is the research focus of Masquelet technology in the treatment of osteomyelitis in the future. Figures and Tables | References | Related Articles | Metrics

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Application and role of human platelet lysate in tissue repair and regeneration Xie Xingqin, Nie Yuqi, Zhang Yi 2022, 26 (28):  4553-4561.  doi: 10.12307/2022.313 Abstract ( 863 )   PDF (808KB) ( 64 )   Save BACKGROUND: Human platelet lysate, rich in ingredients of tissue healing, is a class of biomaterials for tissue repair and regeneration.  OBJECTIVE: To summarize the composition and preparation of platelet lysate and its recent advances in clinical studies and application in human tissue repair.  METHODS: The first author searched PubMed, clinicaltrials.gov, Chinese Clinical Trial Registry, VIP, Wanfang and CNKI databases for relevant articles and clinical trials published from January 2013 to March 2021. The key words were “human platelet lysate, clinical, trial, regeneration, tissue repair, wound healing, biomaterial” in English and Chinese, separately.   RESULTS AND CONCLUSION: Human platelet lysate can be prepared from autologous/allogeneic peripheral blood or umbilical cord blood and contains a variety of components that facilitate cell growth and wound healing. Current clinical studies have demonstrated the safety and efficacy of human platelet lysate, alone or in combination with cell therapy, in tissue repair. Totally 22 ongoing clinical trials in clinicaltrials.gov involve the treatment of several new indications, including post-COVID-19 acute respiratory distress syndrome, peripheral arterial disease, diabetic foot ulcer, facial aesthetics, and so on. In future, the efficacy of these clinical studies will further increase the role of human platelet lysate in tissue regeneration and repair. The combination of human platelet lysate with tissue engineering materials will lay the foundation for its regenerative repair in large tissue defects.   Figures and Tables | References | Related Articles | Metrics

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Application of biomaterial scaffolds in the treatment of spinal cord injury Zhao Xingchang, Song Shiqiang, He Feng, Tang Yujin, Liu Jia 2022, 26 (28):  4562-4568.  doi: 10.12307/2022.314 Abstract ( 466 )   PDF (1415KB) ( 101 )   Save BACKGROUND: Due to the weak regeneration ability after spinal cord injury, it is still a difficult medical problem to repair the damaged spinal cord tissue and normalize its function. The rapid development of biological tissue materials and its wide application in medicine provide new therapeutic ideas and methods for spinal cord injury repair.   OBJECTIVE: To summarize the research situation of biomaterial scaffolds on nerve tissue regeneration and repair after spinal cord injury, and forecast its development trend, so as to explore the methods of spinal cord injury repair and summarize experience. METHODS: The articles published from January 2011 to January 2021 were retrieved using the advanced retrieval function of PubMed database. The search terms were “spinal cord injury; biomaterials; nerve regeneration; material”. By using the advanced retrieval functions of CNKI, Wanfang, VIP and other databases, relevant articles published from January 2011 to January 2021 were searched, and the search terms were “spinal cord injury; biomaterials; scaffolds”.   RESULTS AND CONCLUSION: With further development of the combination of bioengineering research and medicine, biomaterial scaffolds have been widely used in the study of spinal cord injury repair, and the histocompatibility and degradation of biomaterials have been improved. There are many kinds of biomaterials, each of which has its own advantages and disadvantages. It is better to prepare composite scaffolds loaded with seed cells, cytokines or drugs for nerve regeneration. However, how to select the composite scaffold material combination, how to select the seed cells, cytokines or drugs, so as to make the biomaterial scaffold combined with seed cells, cytokines or drugs become the best combination value of in-depth research. In conclusion, biomaterial repair of spinal cord injury is a new idea and may become a breakthrough point to promote the repair of spinal cord injury. Figures and Tables | References | Related Articles | Metrics

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Research progress of gene therapy for vascularization of tissue engineering Li Guangzhao, Chen Rui, Jia Honglin, Ren Liling 2022, 26 (28):  4569-4574.  doi: 10.12307/2022.315 Abstract ( 493 )   PDF (18884KB) ( 43 )   Save BACKGROUND: The rapid formation of functional vascular system in large-scale engineered graft is the basic prerequisite for its successful survival in the host. The vascularization of tissue engineering by genetic engineering technology has the advantages of good therapeutic effect, low cost and high safety. It is of great significance to carry out the research on gene therapy for vascularization of tissue engineering for long-term effective tissue repair. OBJECTIVE: To summarize the current research status and main problems of seed cells, target genes and gene vectors of gene therapy in tissue engineering vascularization so as to further explore the application prospect of gene therapy in tissue engineering vascularization. METHODS: The literature retrieval was conducted on PubMed, Web of Science, and CNKI with the key words of “tissue engineering; vascularization; gene therapy; seed cells; target genes; vectors” in Chinese and English, and 61 articles closely related to this study were selected for the review. RESULTS AND CONCLUSION: Mesenchymal stem cells, vascular endothelial cells and endothelial progenitor cells are the most potential seed cells for vascularization of tissue engineering using gene therapy. They not only have good vascular induction, but also benefit the introduction of many virus and non-viral vectors and the expression of vascularization target genes. Vascular endothelial growth factor, angiopoietin-1, basic fibroblast growth factor, bone morphogenetic protein-2, hypoxia inducible factor-1 α and other vascularization target genes are mainly used to construct efficient and stable vascular network in engineering grafts by means of combination of double/multiple gene, coupling of osteogenesis and angiogenesis, and regulation of upstream gene. Since different viral and non-viral vectors have their own advantages and disadvantages, suitable vectors should be selected according to the efficiency of gene transfection, biological safety, and cost in application. At present, although great progress has been made in the application of gene therapy in tissue engineering vascularization, there are still many key technologies to be broken through for clinical application, such as how to improve the targeted release of target growth factors and reduce the safety risk, which is also the research direction and hot spot of tissue engineering vascularization based on gene therapy in the future. Figures and Tables | References | Related Articles | Metrics

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Electrospun fiber-based nerve tissue engineering scaffold: material, function and structure design strategy Xue Xuexin, Liu Zhepeng 2022, 26 (28):  4575-4580.  doi: 10.12307/2022.316 Abstract ( 518 )   PDF (2104KB) ( 93 )   Save BACKGROUND: In clinical surgery of nerve repair, the donor tissue of autologous nerve grafting is limited, and end-to-end surgical reconnection of the injured nerve ends is not suitable for large gap defects. Therefore, electrospinning nerve scaffold provides a new research idea and direction for nerve tissue engineering.  OBJECTIVE: To summarize the characteristics and manufacturing technology of the electrospinning nerve tissue engineering scaffold in the past three years. METHODS: With “electrospinning nerve scaffold; nerve scaffold; nerve tissue-engineering” as the Chinese and English search terms, articles on the research and application of electrospinning nerve tissue engineering scaffolds were retrieved on CNKI (2015-2021), PubMed (2015-2021), and Web of Science (2015-2021).  RESULTS AND CONCLUSION: By simulating the composition, structure and characteristics of nerve extracellular matrix, the electrospun scaffold can assist the adhesion, proliferation and differentiation of nerve cells, which is an important research direction in the field of neural tissue engineering. The use of matrix materials with affinity for nerve cells gives it good biocompatibility and mechanical properties. Surface modification and modification of the fiber scaffold to make it functional or add substances that assist nerve cell growth can make the scaffold have special properties (conductivity, hydrophilicity, and so on), enhance biocompatibility, improve mechanical properties, and optimize the scaffold degradation rate in the body (slow release of effective growth substances) to promote the adhesion, proliferation and differentiation of nerve cells on the scaffold. Constructing the nano-fiber topography and the geometrical space structure of the scaffold can promote the adhesion and differentiation of nerve cells, provide a microenvironment for the growth of nerve cells, and enhance the nerve repair ability of the electrospun scaffold. Electrospinning nerve tissue engineering scaffolds provide important research ideas and directions for nerve tissue engineering. Figures and Tables | References | Related Articles | Metrics

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Influence of inorganic nano-fillers on the biocompatibility of implanted silicone rubber Tian Youjing, Shi Shuping, Wu Xing 2022, 26 (28):  4581-4586.  doi: 10.12307/2022.317 Abstract ( 525 )   PDF (2108KB) ( 40 )   Save BACKGROUND: Silicone rubber is a common biological material for surgical repair and reconstruction of human tissues and organs. Due to the shortcomings of silicone rubber’s own biocompatibility, inorganic nano-fillers provide new opportunities for the biocompatibility improvement of implanted silicone rubber and the construction of composite materials with specific functions. OBJECTIVE: To review the achievements and deficiencies in the research on biocompatibility of implanted silicone rubber by adding inorganic nano-fillers. METHODS: To enter the keywords “siloxane, silicone rubber, inorganic nano-filler, metal nano-filler, metal oxide nano-filler, carbon nanoparticles” on English biomedical databases PubMed, Web of Science and Medline, and those in Chinese with same meaning as English on Chinese databases Wanfang, CNKI and VIP, to harvest the related articles on inorganic nano-filler modified silicone rubber. The time span was from January 2014 to October 2020 . RESULTS AND CONCLUSION: Metal and their oxide nanoparticles as well as new carbon nano-fillers can improve the biocompatibility of the implanted silicone rubber by body or surface modification, which have a positive impact in the aspects of cell growth, anticoagulation, surface properties, mechanical properties, durability, anti-infective functionalization and so on. In the future, it is necessary to study the mechanism of cell proliferation and migration caused by different nano-fillers on the surface properties of silicone rubber, such as topological structure, charge, and wettability, the regulation strategies and planting of nano-metal bactericides to control the release of cations on the surface of silicone rubber, also the potential nano-toxicity after being implanted. Figures and Tables | References | Related Articles | Metrics

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Application of customized orthopedic insoles in the treatment of flatfoot Zhou Xiangying, Zeng Qing, Liao Zhengwen, Lu Pengcheng, Zou Jihua, Li Shilin, Huang Guozhi 2022, 26 (28):  4587-4592.  doi: 10.12307/2022.318 Abstract ( 723 )   PDF (2184KB) ( 199 )   Save BACKGROUND: Orthopedic insole is widely used in the treatment of flatfeet, for the advantages of non-invasion and continuous intervention. Compared with prefabricated orthopedic insole, customized orthopedic insole has better adaptability, which can effectively support the arch height, adjust the plantar pressure distribution and correct the biological force line.  OBJECTIVE: To introduce the clinical application of customized orthopedic insoles in the treatment of flatfeet in recent years, and the innovations in design and production methods. METHODS: Related articles were searched in PubMed, Web of Science, Embase, Wanfang, VIP and CNKI from January 2006 to December 2020, with the key words of “flatfeet; orthopedic insoles; foot orthoses; customized; personalized; effect; biomechanics; plantar pressure; mechanism’’ in English and Chinese, separately. Eventually, 72 articles that met the criteria were included.  RESULTS AND CONCLUSION: (1) The key of custom-made orthopedic insoles in the treatment of flatfeet is to restore and compensate the foot arch function by selecting appropriate materials and shapes. The specific biomechanical mechanism remains to be explored. (2) With the development of computer-aided design/computer-aided manufacturing and 3D printing technology, the design and production of customized orthopedic insoles tend to be more digital and precise, but there are still shortcomings that need to be optimized. (3) Children with flatfeet can benefit from customized orthopedic insoles more than adults. Patients with obvious clinical symptoms or with multiple foot, ankle and knee diseases should also give priority to customized orthopedic insoles. In the future, more rigorous clinical comparison trials are needed to evaluate the efficacy of customized orthopedic insoles in different flatfoot populations. Figures and Tables | References | Related Articles | Metrics