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08 December 2022, Volume 26 Issue 34 Previous Issue   

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Desferrioxamine-loaded polylactic-co-glycolic acid/hydroxyapatite composite scaffold: vascularization and osteogenesis Zhang Shengmin, Cao Changhong, Wang Ningning, Wang Jing, Li Zhangyi 2022, 26 (34):  5413-5418.  doi: 10.12307/2022.448 Abstract ( 549 )   PDF (1398KB) ( 41 )   Save BACKGROUND: Three-dimensional printed polylactic-co-glycolic acid/hydroxyapatite scaffold is widely used in bone defect repair, because of personalised shapes, excellent osteoconductivity and biocompatibility. However, implanted scaffolds have an adverse effect on bone tissue regeneration due to their poor ability to induce neovascularisation. OBJECTIVE: To verify the osteogenic and angiogenic effects of the desferrioxamine-loaded polylactic-co-glycolic acid/hydroxyapatite composite scaffold. METHODS: The polylactic-co-glycolic acid/hydroxyapatite composite scaffold (control scaffold) and desferrioxamine-loaded polylactic-co-glycolic acid/hydroxyapatite composite scaffold (experimental scaffold) could be fabricated using a low-temperature three-dimensional-printing technique. The microstructure and in vitro degradation of the scaffold were characterized. At the same time, the sustained-release properties of the deferriamine from the desferrioxamine-loaded polylactic-co-glycolic acid/hydroxyapatite composite scaffold were detected. The rat derived adipose stem cells were seeded on the two groups of scaffolds respectively, and the cells inoculated on the culture plate were used as the control group. Cytoskeleton observation, cell proliferation test, staining of live and dead cells, qRT-PCR detection, and immunofluorescence analysis were performed. RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that the control scaffold and experimental scaffold had uniformly distributed macroporous structure, and there was no obvious difference. The pore size of the scaffolds was about 510 μm. (2) In vitro degradation experiments showed that the degradation rate of the control scaffold and experimental scaffold was less than 10% at 8 weeks, and the pH value remained relatively stable and always remained at 7.1 to 7.4. (3) In vitro sustained-release experiments showed that the deferoxamine had a burst release from the experimental scaffolds within 2 weeks and sustained a steady level, at about 75% within 8 weeks. (4) It can be seen under a fluorescent inverted microscope that the adipose stem cells on the two scaffolds were spindle-shaped and spread larger. Scanning electron microscopy showed that there were many pseudopods of cells on both scaffolds, and the cells were spread well on the surface of the scaffolds. (5) CCK-8 assay showed there was no difference in cell proliferation among the three groups (P < 0.05). (6) qRT-PCR showed that compared with the control group and control scaffold group, the gene expression of vascular endothelial growth factor and osteocalcin in the experimental scaffold group was increased (P < 0.01). Immunofluorescence analysis showed that compared with the control group and the control scaffold group, the protein expression of vascular endothelial growth factor and osteocalcin in the experimental scaffold group increased (P < 0.01). (7) The results showed that the three-dimensional-printed desferrioxamine-loaded polylactic-co-glycolic acid/hydroxyapatite composite scaffold was expected to play a good dual role in osteogenesis and vascularization. Figures and Tables | References | Related Articles | Metrics

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Effect of artificial bone with multi-scale hydroxyapatite/chitosan microtubule structure on rabbit bone defect repair and angiogenesis Long Zhisheng, Xiong Long, Gong Feipeng, Li Jingtang, Zeng Jianhua, Deng Ying, Lan Min, Kong Weihao, Chen Gang 2022, 26 (34):  5436-5441.  doi: 10.12307/2022.452 Abstract ( 486 )   PDF (1180KB) ( 35 )   Save BACKGROUND: Early studies have confirmed that multi-scale hydroxyapatite/chitosan microtubules are excellent in osteogenesis. Angiogenesis is critical in the process of osteogenesis. It is significant to explore the role of tube structure with multi-scale microtubules in its vascularization and related mechanisms. OBJECTIVE: To explore the effect of multi-scale hydroxyapatite/chitosan microtubule structure on rabbit bone defect repair and vascularization. METHODS: Multi-scale hydroxyapatite/chitosan microtubule structure and hydroxyapatite/chitosan monomer structure were constructed and co-cultured with bone marrow mesenchymal stem cells for 21 days. The adsorption ability of the material to cells and the cell state were observed under the electron microscope. Bone defect models were made on the radius of 48 adult New Zealand white rabbits. Rabbits in the experimental group (n=24) were implanted with multi-scale hydroxyapatite/chitosan microtubule structure material. Rabbits in the control group (n=24) were implanted with hydroxyapatite/chitosan monomer structure material. Emission computed tomography, X-ray, histomorphological examination, and immunohistochemistry for CD31 and vascular endothelial growth factor protein detection were performed at 4, 8, and 12 weeks after surgery. The animal experiment was approved by the Ethics Committee of Jiangxi Provincial People’s Hospital. RESULTS AND CONCLUSION: (1) Under the electron microscope, the multi-scale hydroxyapatite/chitosan microtubule structure materials were interlinked and had a good spatial structure. The number of bone marrow mesenchymal stem cells on the multi-scale hydroxyapatite/chitosan microtubule structure material was more than that on the hydroxyapatite/chitosan monomer structure material. (2) Emission computed tomography exhibited that the blood pool image was higher in the experimental group than that in the control group at various time points after surgery (P < 0.05). (3) X-ray films showed that the formation of multi-scale microtubules was more obvious in the experimental group than that in the control group. (4) Hematoxylin-eosin staining demonstrated that at 12 weeks after surgery, the appearance of osteoblasts and angiogenesis was obvious in the experimental group; only a few regenerated blood vessels and osteoblast attachment were found at the fractured end in the control group. Immunohistochemistry for CD31 exhibited that the microvessel density of the experimental group was higher than that of the control group at each time point (P < 0.05). (5) Western blot assay results displayed that the expression of vascular endothelial growth factor protein in the experimental group was higher than that in the control group at each time point (P < 0.05). (6) The results showed that the multi-scale hydroxyapatite/chitosan microtubule structure had better osteogenesis and vascularization ability than its monomer structure. Figures and Tables | References | Related Articles | Metrics

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Preparation of silver-loaded nanohydroxyapatite/polycaprolactone composite nanofiber scaffold and its osteogenic and antibacterial properties Cao Fei, Hui Min, Dong Xiling, Wang Le, Wang Zuxu, Zhang Min, Zhang Xiaoming, Liu Tongbin 2022, 26 (34):  5461-5467.  doi: 10.12307/2022.456 Abstract ( 437 )   PDF (2356KB) ( 34 )   Save BACKGROUND: Bone tissue has the function of self-renewal, reconstruction and repair of tissue defects. However, when a large area of severe bone defect occurs, bone grafts or bone substitutes are often needed to reconstruct the defect, which increases the risk of bone infection around the implant.  OBJECTIVE: To prepare nanohydroxyapatite/polycaprolactone composite nanofiber scaffolds with different silver concentrations to determine the silver concentration that promotes cell proliferation and has antibacterial properties.  METHODS: Nanohydroxyapatite/polycaprolactone composite nanofiber scaffolds with different silver concentrations (0, 0.001, 0.01, 0.1 mol/L) were prepared by using electrospinning technology. The microscopic morphology and elemental composition of scaffolds of four groups were shown by scanning electron microscopy, energy dispersive spectroscopy and transmission electron microscope. MC3T3-E1 osteoblasts were co-cultured with four groups of scaffolds to study the effect of sample scaffolds on the cell proliferation and osteogenic differentiation. Four groups of scaffolds were co-cultured with Staphylococcus aureus (ATCC25923) and Escherichia coli (ATCC25922) to study the antibacterial properties of scaffolds by the formation of antibacterial circle and antibacterial rate. RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that the four groups of electrospinning films were more continuous and uniform in diameter. The electrospinning filaments displayed a mesh-like structure, in which pore structures of different sizes were dispersed. As the silver-loaded content of the scaffold increased, the diameter of the nanofibers gradually increased. Transmission electron microscope showed that the silver-loaded scaffold nanofibers were uniformly dispersed with black silver nanoparticles, and the particle size diameter was (46±24) nm. (2) CCK-8 assay showed that compared with the unloaded silver scaffolds, silver-loaded 0.001, 0.01 mol/L nanofiber scaffolds could promote osteoblast proliferation. Silver-loaded 0.1 mol/L nanofiber scaffolds inhibited osteoblast proliferation. Nucleus and cytoskeleton staining showed that silver-loaded 0, 0.001, and 0.01 mol/L nanofiber scaffolds facilitated the extension of osteoblast morphology. Silver-loaded 0.1 mol/L nanofiber scaffolds were not conducive to the extension of osteoblast morphology. (3) Alkaline phosphatase staining showed that silver-loaded 0, 0.001, and 0.01 mol/L nanofiber scaffolds were beneficial to osteoblast differentiation, and silver-loaded 0.1 mol/L nanofiber scaffolds inhibited osteoblast differentiation. (4) Antibacterial circle experiment showed that the unloaded silver scaffolds had no antibacterial properties. As the silver-loaded content of the scaffold increased, the antibacterial properties of silver-loaded scaffolds increased. Antibacterial rate experiment proved that silver-loaded 0.01 mol/L nanofiber scaffolds had strong antibacterial activity. (5) The results confirm that the silver-loaded 0.01 mol/L nanohydroxyapatite/polycaprolactone composite nanofiber scaffold has both good biological activity and excellent antibacterial properties.  Figures and Tables | References | Related Articles | Metrics

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Effects of alkali-and-heat treatment combined with ultraviolet photofunctionalization pure titanium on osteoblast activity Zheng Rui, Sun Yong 2022, 26 (34):  5486-5491.  doi: 10.12307/2022.460 Abstract ( 377 )   PDF (3397KB) ( 26 )   Save BACKGROUND: After alkali-and-heat treatment on the titanium surface, a layer of sodium titanate gel will be formed to promote the formation of bone-like apatite, thereby combining with living bone. The titanium surface will form a hydrophilic surface after ultraviolet photofunctionalization, which can increase the surface free energy, promote the adsorption of protein in body fluid, and further promote the adhesion and reaction between cells and titanium surface.   OBJECTIVE: To explore the physical and chemical properties of alkali-and-heat treatment combined with ultraviolet photofunctionalization pure titanium surface, and its effects on adhesion, proliferation and differentiation of MC3T3-E1 cells.   METHODS: TA2 pure titanium discs were randomly divided into three groups. The group A received acid etching treatment. The group B received acid etching + alkali-and-heat treatment. The group C received acid etching + alkali-and-heat + ultraviolet photofunctionalization treatment. The microscopic morphology, element composition, and static contact angle were characterized in the three groups of titanium discs. MC3T3-E1 cells in logarithmic growth phase were inoculated on the surface of three groups of titanium discs. CCK-8 assay was used to detect cell proliferation. Cell adhesion was observed under scanning electron microscope. After osteogenic induction and culture, the alkaline phosphatase activity, the secretion of type I collagen, and the formation of mineralized nodules were detected. RESULTS AND CONCLUSION: (1) Under scanning electron microscope, the surface of group A was rough and honeycomb shaped, with relatively uniform pore. The surfaces of group B were distributed with loosely nano-level pores and brain-circuit like gullies. The gullies and pores were cross-linked with each other. The surfaces of group C also had nanoporous network structure, and the distribution and size of gullies and pores were not significantly different from that of group B. (2) C, O, Ti, and P elements were both found on the surfaces of the three groups, and Ca element was also detected on the surfaces of groups B and C, but Ca element was scarcely found on the surface of group A. The static contact angle of group A was the smallest, while that of group C was the largest. (3) Scanning electron microscope showed that there were more cells on the surface of the titanium plates in each group at 24 hours after injection. The cells in groups A and B were long fusiform, triangular or flat. The cells in group C were larger in diameter and had several pseudopods, and the flat polygons were spread into a thin layer on the surface of the titanium plates, interconnected, and unable to distinguish cell boundaries. (4) The cell proliferation on the surface of titanium plates in group C was faster than that in groups A and B, and the alkaline phosphatase activity, type I collagen secretion and the number of mineralized nodules in group C were higher than those in groups A and B. (5) The results showed that alkali-and-heat treatment combined with ultraviolet photofunctionalization could effectively improve the physical and chemical properties of pure titanium surface and promote the biological activity of osteoblasts. Figures and Tables | References | Related Articles | Metrics

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Construction of chitosan/mineralized collagen porous scaffold, osteogenic differentiation in vitro and biocompatibility Sun Xirao, Bao Jiaxin, Wang Chengyue 2022, 26 (34):  5498-5503.  doi: 10.12307/2022.462 Abstract ( 517 )   PDF (1498KB) ( 23 )   Save BACKGROUND: Chitosan material has good biocompatibility, biodegradability and low immunogenicity, but its activity is poor; mineralized collagen material has good biocompatibility, but its mechanical properties are insufficient, so their combination may show better mechanical properties and osteogenic activity. OBJECTIVE: To construct a chitosan/mineralized collagen porous scaffold with different compositions and to show surface characteristics and biocompatibility. METHODS: The porous scaffolds with different mass ratios (2:1, 1:1) of chitosan and mineralized collagen were prepared by freeze-drying. Scanning electron microscope, energy dispersive spectrometer, X-ray diffraction, and Fourier infrared Spectrum were used to show the surface morphology, element composition, and structure of porous scaffolds in each group. The mouse osteoblast precursor cells were directly inoculated on the surface of the scaffolds of three groups, and the cell adhesion was observed by scanning electron microscope. The blank control and three groups of material extracts were co-cultured with mouse osteogenic precursor cells. CCK-8 assay, phalloidin staining, and alkaline phosphatase analysis were applied to analyze the effect of materials on proliferation and differentiation of mouse osteogenic precursor cells.   RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that there were uniform pores on the surface of chitosan composite materials. The interface of chitosan/mineralized collagen porous scaffold was tightly bonded. Simultaneously, as the content of chitosan in the scaffold decreased, the agglomeration of mineralized collagen particles in the scaffold became more obvious. Energy dispersive spectrometer displayed that elements on the surface of the simple chitosan scaffold were mainly carbon, nitrogen and oxygen. The calcium and phosphorous elements on the surface of the scaffold material gradually increased after mineralized collagen was added. X-ray diffraction and Fourier infrared Spectrum exhibited that chitosan and mineralized collagen were physically combined. (2) Scanning electron microscopy showed that the cells adhered and spread normally on the surface of the three groups of scaffold materials. Among them, the number of cells attached to the surface of the simple chitosan scaffold was less. (3) CCK-8 assay displayed that compared with the simple chitosan porous scaffold extract, two ratios of chitosan/mineralized collagen porous scaffold extract could promote the proliferation of mouse osteogenic precursor cells. Cytoskeleton staining showed that two ratios of chitosan/mineralized collagen porous scaffold had high cell density of the extract liquid group; the cell filament feet were connected to each other; and the expression of microfilament actin was clear. (4) The alkaline phosphatase activity test demonstrated that compared with the simple chitosan porous scaffold extract, the two ratios of chitosan/mineralized collagen porous scaffold extract can promote osteogenic differentiation of mouse osteogenic precursor cells. (5) It is concluded that chitosan/mineralized collagen porous scaffold can effectively promote proliferation and differentiation of mouse osteoblast precursor cells.  Figures and Tables | References | Related Articles | Metrics

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3D bio-printing methylacrylated gelatin hydrogel scaffolds promote the repair of subchondral bone defects Lu Dongdong, Zhu Tianfeng, Zhang Yijian, Zhao Zhijian, Liu Yang, Shen Xu, Zhu Xuesong 2022, 26 (34):  5454-5460.  doi: 10.12307/2022.455 Abstract ( 669 )   PDF (2140KB) ( 48 )   Save BACKGROUND: Subchondral bone plays an important role in normal physiological activities of joints and is difficult to repair once it is damaged. Traditional bone cement and autologous bone grafting treatment methods have certain limitations. OBJECTIVE: To explore the efficacy of bone marrow mesenchymal stem cells or chondroprogenitor cells encapsulated in 3D bio-printing methylacrylated gelatin hydrogel scaffolds to repair subchondral bone defects. METHODS: Chondroprogenitor cells were obtained by fibronectin sorting method and rabbit bone marrow mesenchymal stem cells were obtained by whole bone marrow adherent method. The proliferation, osteogenic, chondrogenic, and adipogenic differentiation abilities were compared between the two groups. Methylacrylated gelatin hydrogel scaffolds loaded with bone marrow mesenchymal stem cells and chondroprogenitor cells were prepared by 3D bio-printing. After osteogenic induction and culture, the survival rate of cells in the scaffold was analyzed by live-dead staining. The osteogenic gene expression of the scaffold was detected by qRT-PCR. Subchondral bone defects with a diameter of 5 mm and a depth of 5 mm were prepared at the bilateral knee joints of 16 New Zealand white rabbits. They were divided into four groups. Group A was not treated. Group B was implanted with methylacrylated gelatin hydrogel scaffold. Group C was implanted with a hydrogel scaffold loaded with bone marrow mesenchymal stem cells. Group D was implanted with a hydrogel scaffold loaded with chondroprogenitor cells. Micro-CT scanning and histological observation of the bone defect area were performed at 6 and 12 weeks after surgery.   RESULTS AND CONCLUSION: (1) The proliferation, osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells were higher than those of chondroprogenitor cells. The chondrogenic differentiation of bone marrow mesenchymal stem cells was weaker than that of chondroprogenitor cells. (2) Bone marrow mesenchymal stem cells and chondroprogenitor cells in the hydrogel scaffolds showed good viability. The mRNA expression of osteogenic related genes of bone marrow mesenchymal stem cells including osteocalcin, osteopontin and runt-related transcription factor 2 in the scaffold was higher than that of chondroprogenitor cells (P < 0.05). (3) The micro-CT scan of the animal repair experiment showed that the bone tissue formed in Group C was the most, and the trabecular bone structure was formed at 12 weeks after the operation. The shape of the new bone was similar to the surrounding natural cancellous bone; the new bone tissue in groups A and B was the least. The Safranin O/fast green staining results showed that at 6 weeks after surgery, only a small amount of new bone was formed in the subchondral bone area of Groups C and D. At 12 weeks after surgery, bone matrix was formed in Groups A and B. Group C showed massive repairs of subchondral bone. More new bone formation was found in Group C compared with Group D. (4) Results suggested that bone marrow mesenchymal stem cells and 3D bio-printing methylacrylated gelatin hydrogel scaffold were suitable for seed cells and scaffolds for bone tissue engineering.  Figures and Tables | References | Related Articles | Metrics

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Modified coaxial 3D-printed akermanite scaffold with hollow-pipe structure Liu Chang, Xu Ling 2022, 26 (34):  5425-5429.  doi: 10.12307/2022.450 Abstract ( 502 )   PDF (1347KB) ( 38 )   Save BACKGROUND: With the continuous development of three-dimensional (3D) printing technology and bone tissue engineering, more and more 3D printed scaffolds have applied in study of bone tissue engineering. The 3D printed scaffold with hollow pipe structure has the advantages of vascular growth and nutrient delivery, which is worthy of further study. OBJECTIVE: To investigate the effect of ionic components released by akermanite on osteogenic differentiation of rat bone marrow mesenchymal stem cells and migration of human umbilical vein endothelial cells and fabricate the 3D-printed akermanite scaffold with hollow-pipe structure with coaxial 3D printing technology.    METHODS: The rat bone marrow mesenchymal stem cells and human umbilical vein endothelial cells were cultured with different concentrations of akermanite extracts (1/4, 1/8 and 1/16). The proliferation of rat bone marrow mesenchymal stem cells was detected by CCK-8 assay. Osteogenic differentiation of human umbilical vein endothelial cells was investigated by alkaline phosphatase staining and RT-qPCR. Transwell assay was used to observe the migration of human umbilical vein endothelial cells in response to different concentrations of akermanite extracts. The akermanite scaffold with hollow-pipe structure was prepared using a modified printer nozzle with a core/shell structure with the printing system. The scaffolds were immersed into deionized water and the extracts were collected at set time points. The concentration of ionic products was detected with inductively coupled plasma atomic emission spectrometry.  RESULTS AND CONCLUSIOIN: (1) CCK-8 assay indicated that the akermanite extracts had a concentration and time-related effect on promoting the proliferation of bone marrow mesenchymal stem cells. (2) Alkaline phosphatase staining showed that the akermanite extracts had a concentration-related effect on the alkaline phosphatase activity of rat bone marrow mesenchymal stem cells. RT-qPCR indicated that the extracts had a concentration-related effect on the mRNA expression of alkaline phosphatase, collagen-1 and Runx2 of bone marrow mesenchymal stem cells. (3) The akermanite extracts had a concentration-related effect on the migration of human umbilical vein endothelial cells. (4) The scaffolds would continuously release the Ca, Mg and Si ions during immersion into deionized water for 30 days. The akermanite scaffold with hollow pipes was conducive to the release of biologically active ions and had high concentration. (5) The result showed that the akermanite scaffolds with hollow pipes were successfully prepared with the modified 3D printer. The ionic products released by scaffolds had an obvious effect on osteogenesis of rat bone marrow mesenchymal stem cells and promoted migration of human umbilical vein endothelial cells, thereby accelerating vascular regeneration. Figures and Tables | References | Related Articles | Metrics

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Hemostatic effect of macroporous polysaccharides composite hemostatic materials on small-artery severed injury Xu Lin, Cheng Gangyi, Li Hongwei, Wang Hongjian, Lin Minghui, Guo Hongwei, Lin Lianfeng, Xu Ling 2022, 26 (34):  5442-5447.  doi: 10.12307/2022.453 Abstract ( 453 )   PDF (1264KB) ( 156 )   Save BACKGROUND: The hemostatic performance of absorbable hemostatic materials for arterial bleeding cannot meets for the clinical demands.  OBJECTIVE: To study the hemostatic effect of macroporous polysaccharides composite hemostatic materials on small artery hemorrhage.  METHODS: The rabbit model of arteriolar hemorrhage was established by severing the femoral artery and randomly divided into two groups. The experimental group (n=10) was treated with macroporous polysaccharides composite hemostatic materials, and the control group (n=7) was treated with commercial microporous polysaccharide hemostatic powder. After operation, hemostatic success rate, blood loss, blood routine test, liver and kidney function index were recorded and hematoxylin-eosin staining was used to observe wound tissue.  RESULTS AND CONCLUSION: (1) The success ratio of hemostasis in experimental group was higher than that in the control group (90%, 43%, P < 0.05). There was no significant difference in intraoperative blood loss between the two groups (P > 0.05). (2) The blood routine and liver and kidney function index test results within 180 days after operation showed that the change trend of each index of the two groups was basically the same, and the two hemostatic materials did not cause obvious liver and kidney dysfunction, nor did it cause purulent or inflammation in the degradation and absorption process. (3) The hematoxylin-red staining of the wound tissue 90 days after the operation showed that the tissues in the experimental group were evenly stained; the muscle fiber morphology and structure were normal; the boundaries were clear; and the arrangement was regular. There was no obvious abnormality in the interstitium, and no scars in the wound. In the control group, the tissues were uniformly stained; the morphology and structure of muscle fibers were normal; the boundaries were clear; and the arrangement was regular. There was no obvious abnormality in the interstitium, but there were more scars locally. (4) These results suggest that effectiveness of the macroporous polysaccharides composite hemostatic materials is higher than that of the commercial hemostatic powder. The safety is not inferior to that of the commercial hemostatic powder. Therefore, the macroporous polysaccharides composite hemostatic materials can be used for hemostasis in vivo. Figures and Tables | References | Related Articles | Metrics

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Basic fibroblast growth factor combined with poly(lactic acid)/collagen scaffold for urethral defect in rabbits Liu Pei, Zhang Guanying, Yu Quanfeng, Li Zeyu, Han Guangye, Wu Chunlei 2022, 26 (34):  5468-5474.  doi: 10.12307/2022.457 Abstract ( 491 )   PDF (2003KB) ( 28 )   Save BACKGROUND: As one of the effective angiogenic factors, basic fibroblast growth factor can not only increase the blood perfusion of ischemic tissues and accelerate the regeneration of tissue microvessels, but also improve the formation of blood vessels in muscle tissues and increase the blood perfusion of muscles.  OBJECTIVE: Basic fibroblast growth factor was incorporated into poly(lactic acid)/collagen scaffold to repair rabbit urethral defects and to improve the ability of tissue engineered scaffolds to induce urethral regeneration.  METHODS: The electrospun poly(lactic acid)/collagen urethral scaffold and the electrospun poly(lactic acid)/collagen scaffold loaded with basic fibroblast growth factor were prepared and named as control scaffold and experimental scaffold, respectively. The in vitro release properties of the scaffolds were tested. The third passage of rabbit adipose derived mesenchymal stem cells was seeded on the two scaffolds for 7 days. CCK-8 assay, cell adhesion test, and cell live-dead staining were performed respectively. Twenty-four adult male New Zealand white rabbits were used to establish a 5 cm long urethral defect model and randomly divided into two groups (n=12). The control scaffold + adipose derived mesenchymal stem cell complex and the experimental scaffold + adipose derived mesenchymal stem cell complex were implanted, respectively. At 12 and 24 weeks after operation, retrograde urethrography and histology were performed. RESULTS AND CONCLUSION: (1) In vitro sustained release experiment: Basic fibroblast growth factor was released at an average rate of 2.5 ng/d in the first 6 days, 1.52 ng/d from the seventh to fourteenth days, and 1.12 ng/d thereafter. The release rate gradually decreased after 21 days. (2) In vitro cell experiments showed that the cell proliferation rate on the experimental scaffold was faster than that on the control scaffold (P < 0.05). Adipose-derived mesenchymal stem cells could adhere to the surfaces of the two scaffolds, grow well and protrude pseudopodia, among which the cells on the experimental scaffold proliferated rapidly. The survival rate of the cells on the experimental scaffolds was higher than that of the control scaffold (P < 0.05). (3) In vivo experimental results: At 24 weeks postoperatively, urethral angiography exhibited that there was no urethral stricture in the experimental scaffold group, and mild urethral stricture was seen in the control scaffold group. Histological observation demonstrated that at 24 weeks after operation, there was a thick and complete epithelial layer in the experimental scaffold group, with a large number of muscle fiber bundles and blood vessels. In the control scaffold group, there was a thin epithelial layer, with a small number of muscle fiber bundles and blood vessels. (4) The results confirm that electrospun poly(lactic acid)/collagen scaffold loaded with basic fibroblast growth factor for repairing rabbit urethral defects could promote local angiogenesis, improve local urethral microenvironment and promote urethral regeneration.basic fibroblast growth factor; poly(lactic acid); collagen; scaffold; urethral defect; urethral regeneration; tissue engineering Figures and Tables | References | Related Articles | Metrics

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Preparation and in vitro release of manganese-based metal-organic framework materials loaded with baicalin Lin Lingqi, Chen Jin, Qian Kun, Zhao Liang, Shi Yijie 2022, 26 (34):  5475-5481.  doi: 10.12307/2022.458 Abstract ( 415 )   PDF (1647KB) ( 99 )   Save BACKGROUND:  In recent years, metal-organic framework materials have been widely used in the field of drug carriers. The core metal ions are generally dominated by iron, cobalt, copper, and zinc ions, but there is still a big gap in the study of metal organic frameworks based on the equally important manganese ions.  OBJECTIVE: To synthesize a manganese-based metal organic framework as a drug carrier to load the anti-tumor drug baicalin, and to study its in vitro release behavior.  METHODS: The manganese-based metal organic framework [Mn3(μ3-ade)2(OA)2] synthesized by a hydrothermal stirring method was worked as a drug carrier and loaded the anti-tumor drug baicalin. Before and after loading the drug, the structure, morphology and particle size of the samples were analyzed by X-ray powder diffraction, infrared spectroscopy, scanning electron microscope, and X-ray photoelectron spectroscopy, and the drug-loading and drug release performance of manganese-based metal organic frameworks were investigated.  RESULTS AND CONCLUSION: (1) When the crystallization time was 15 hours, the diffraction peak position, crystallinity and diffraction peak intensity of the synthesized sample were the best. Manganese-based metal organic framework was stable at pH=5.8. (2) After loading the drug, the crystal structure of the manganese-based metal organic framework changed significantly, confirming the successful loading of the drug. Under the conditions that the mass ratio of carrier to drug was 1:1 and the loading time was 8 hours, the drug loading rate was the largest, which could be up to (43.12±1.93)%. (3) The in vitro release test results showed that the cumulative release rate of [Mn3(μ3-ade)2(OA)2] in a release medium whose pH was 5.8 simulated the tumor microenvironment was (71.84±5.96)%. The cumulative release rate in a release medium whose pH was 7.4 simulated the human microenvironment was (48.90±7.21)%. (4) The results show that during the drug loading, the crystal structure and morphology are transformed to achieve the successful loading of baicalin, and the drug release can be controlled according to the pH response, thereby forming an effective drug delivery system. Figures and Tables | References | Related Articles | Metrics

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ICON penetrating resin for treatment of dental fluorosis: 1-year follow-up Sun Honglei, Qi Fengna, Cheng Ruiqing 2022, 26 (34):  5419-5424.  doi: 10.12307/2022.449 Abstract ( 647 )   PDF (1105KB) ( 97 )   Save BACKGROUND: Dental fluorosis seriously affects the aesthetics of patients, and traditional oral filling materials have defects. OBJECTIVE: To evaluate the clinical efficacy of Icon (DMG, Hamburg, Germany) penetrating resin in the treatment of dental fluorosis.  METHODS: ICON penetrating resin was used to treat dental fluorosis in 30 patients (200 teeth in total) admitted to Hebei Eye Hospital from December 2018 to December 2019. After treatment, patients’ subjective feelings about the treatment, including satisfaction with aesthetics, tooth sensitivity after treatment, and dignity with the treatment process, were counted through a questionnaire. The relationship between the size of the lesion, the tooth surface index of fluorosis, and the number of dental erosion required for the filling was calculated to investigate the effect of the lesion on the treatment.  RESULTS AND CONCLUSION: (1) The aesthetic satisfaction of 30 patients was higher at 3, 6, and 9 months after treatment than that before and immediately after treatment (P < 0.05). Among 30 patients, dentin hypersensitivity was not detected in 19 patients after resin restoration, and dentin sensitivity disappeared within 72 hours in 11 patients. All patients were satisfied with the treatment. (2) Before treatment, the proportion of tooth surface index of fluorosis scoring 1, 2, and 3 was 65.50%, 30.50%, and 4.00%,respectively. Immediately after treatment, the proportion of the tooth surface index of fluorosis scoring 0, 1, and 2 was 83.00%, 16.00%, and 1.00%, respectively. Spearman rank correlation analysis demonstrated a correlation between the number of dental erosion during the operation, the size of the lesion, and the tooth surface index of fluorosis. (3) It is concluded that ICON infiltration resin has a highly effective and stable effect for treating dental fluorosis. However, the size of the fluorosis lesion and the tooth surface index of fluorosis may affect the number of dental erosion during the procedure, which also needs to be taken into account by the practitioner. Figures and Tables | References | Related Articles | Metrics

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Structure characterization and performance evaluation of modified bovine pericardial scleral biological patch with genipin Liu Xiaojun, Li Zihong, Guo Wenyuan, Han Ying, Xu Yuyin, Zhou Jing, Wang Junmin 2022, 26 (34):  5430-5435.  doi: 10.12307/2022.451 Abstract ( 449 )   PDF (1484KB) ( 38 )   Save BACKGROUND: At present, the application of biological patch in posterior scleral reinforcement has received extensive attention. The structure and performance of the biological scleral mesh are directly related to the success rate of the implant, so it is very important to characterize the structure and evaluate the performance of the biological mesh.  OBJECTIVE: To investigate the structure and properties of the modified bovine pericardial scleral biological patch with genipin.  METHODS: The structures of fresh group, acellular group and genipin group were characterized by optical microscope, scanning electron microscopy, infrared spectrometer, and X-ray diffraction. Their physical index was evaluated through the determination of mechanical properties, water content rate and thermal stability. In addition, the biocompatibility of bovine pericardium patch in genipin group was evaluated by genetic toxicity test.  RESULTS AND CONCLUSION: (1) The results of histology and scanning electron microscopy showed that the cellular components in the material were effectively removed by acellular treatment. After acellular treatment and genipin modification, the collagen fiber structure was well preserved and orderly without destroying the stable structure of the collagen fiber. (2) Infrared spectrometer and X-ray diffraction demonstrated that there were more amide groups in the collagen fiber of bovine pericardium in genipin group. In addition, the crystal phase of bovine pericardium in fresh and acellular groups was incomplete and the crystallization was poor, while its crystallinity of genipin group was improved. (3) Tensile strength of bovine pericardium in genipin group was significantly higher than that of acellular group (P < 0.05); and elongation at break was significantly lower than that in acellular group (P < 0.05). (4) There was no significant difference in the water content rate between genipin group and acellular group (P > 0.05). (5) The temperature of thermal denaturation in genipin group was higher than that in acellular group. (6) The in vitro mammalian chromosome aberration test in genipin group showed negative result. (7) The results suggested that modified bovine pericardium patch for posterior scleral reinforcement with genipin had good physical and chemical properties and biocompatibility.  Figures and Tables | References | Related Articles | Metrics

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In vivo neocollagenesis of injectable poly(L-lactic acid) microspheres Zhang Yixin, Luo Qian, Liang Hanwen, Chen Jianlin, Zhao Nan, He Bin 2022, 26 (34):  5448-5453.  doi: 10.12307/2022.454 Abstract ( 1145 )   PDF (1833KB) ( 117 )   Save BACKGROUND: Poly(L-lactic acid) (PLLA) microparticle (Sculptra®) has been approved by FDA as the dermal filler to regenerate collagen for anti-aging purpose. Because of its irregular particle shape, it is prone to excessive inflammation. OBJECTIVE: To investigate the effects of irradiation on the molecular weight, size and morphology of the poly(L-lactic acid) microspheres, as well as the foreign body reaction and the neocollagenesis stimulation of the poly(L-lactic acid) microspheres dermal filler implanted subcutaneously into back of rabbits. METHODS: Microspheres were prepared by the emulsion-solvent evaporation method and utilized as the dermal filler with the same Sculptra’®s formula. The filler was sterilized by irradiation at 25 and 50 kGy, separately and the molecular weight, size and morphology of the microspheres were analyzed. The MTT assay was used to detect the effects of the microspheres at different concentrations (50, 100, 250, and 500 mg/L calculated by the concentration of microspheres) on the proliferation of mouse fibroblasts. The 25 kGy irradiated dermal filler (experimental group) and saline (control group) were injected into the back of the rabbit subcutaneously. Hematoxylin-eosin staining, Masson staining, and immunofluorescence staining of CD68, type I collagen and type III collagen were performed on the back tissue of the injection site at the set time points.  RESULTS AND CONCLUSION: (1) With the increase of the radiation dose, the viscosity, viscosity-average molecular weight and number-average molecular weight of the microspheres decreased significantly, but the irradiation sterilization did not cause significant changes in the particle size and morphology of the microspheres. (2) MTT assay results demonstrated that when the mass concentration of the filler was lower than 250 mg/L, the cell survival rate was all >90%. Even when the material mass concentration reached the highest level 500 mg/L, the cell survival rate was still higher than 80%. Incubation for 72 hours also did not produce significant cytotoxicity. (3) In animal experiments, hematoxylin-eosin staining and CD68 immunofluorescence staining revealed that the filler caused slight inflammatory response from 0.5 to 4 months after implantation, and the inflammatory response reached the highest level at 6 months after implantation. Some microspheres were degraded to irregular shape or with pores on the surface, and the microspheres were degraded completely at 9 months after implantation. (4) In animal experiments, Masson staining and immunofluorescence staining of type I collagen and type III collagen exhibited that at 4 months after implantation, type I collagen was mainly around the microspheres, and type III collagen was mainly at the periphery. At 6 months after implantation, type I collagen near the microspheres increased, and type III collagen at the periphery increased. At 9 months after implantation, the fibrous encapsulation was mainly composed of type I collagen, and the ratio of type I collagen to type III collagen was close to the same at the periphery. (5) The results indicate that injectable poly(L-lactic acid) microsphere filler can stimulate collagen regeneration and can also reduce the degree of inflammatory response.  Figures and Tables | References | Related Articles | Metrics

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Relationship between graft diameter and knee function in anterior cruciate ligament reconstruction Luo Xuehui, Du Shaolong 2022, 26 (34):  5482-5485.  doi: 10.12307/2022.459 Abstract ( 376 )   PDF (736KB) ( 26 )   Save BACKGROUND: The functional rehabilitation of patients after anterior cruciate ligament reconstruction is related to various factors, such as different reconstruction methods, anterior cruciate ligament graft shape and diameter, and different types of anterior cruciate ligament graft. Related clinical studies suggest that the diameter of the graft is 7-10 mm; the larger the diameter, the better the knee joint recovery function and the fewer complications. OBJECTIVE: To study the relationship between graft diameter and knee function in anterior cruciate ligament reconstruction.   METHODS: A total of 90 patients with anterior cruciate ligament rupture in Sanshui Hospital of Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine from March 2018 to January 2020 were selected. Autogenous tendons were used for anterior cruciate ligament reconstruction. According to the diameter size of the autologous tendon braided in the knee joint, they were divided into 7 mm group (n=26), 8 mm group (n=43) and 9 mm group (n=21). The patients were followed up for 1 year. IKDC and Lysholm were used to assess knee function. The stability of knee joint was evaluated by KT-1000 and posterior cruciate ligament index. The protocol was approved by the Ethics Committee of Sanshui Hospital of Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine.  RESULTS AND CONCLUSION: (1) IKDC score and Lysholm score of the 8 mm group were higher than those of the 7 mm group and the 9 mm group (P < 0.05). There was no significant difference between the 7 mm group and the 9 mm group in the IKDC score and Lysholm score (P > 0.05). (2) Tibial anteversion distance in KT-1000 test and the posterior cruciate ligament index of the 7 mm group were greater than those of the 8 mm group and 9 mm group (P < 0.05). The posterior cruciate ligament index of the 8 mm group was less than that of the 9 mm group (P < 0.05). There was no significant difference in tibial anteversion distance in KT-1000 test between the 8 mm group and 9 mm group (P > 0.05). (3) Results suggest that in patients with simple anterior cruciate ligament injury of the knee, the reconstructed diameter of 8 mm and 9 mm has better stability of the knee joint. The reconstructed diameter of 8 mm has better function. Smaller or larger diameter may affect the functional recovery of patients with certain factors. Figures and Tables | References | Related Articles | Metrics

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Comparison of clinical application of skull repair materials of three-dimensional digital shaping polyether ether ketone and titanium mesh Wang Yiming, Yang Fengdong, Mao Wenbin, Jia Xin, Wei Shuxin, Wei Xinting 2022, 26 (34):  5492-5497.  doi: 10.12307/2022.461 Abstract ( 425 )   PDF (918KB) ( 33 )   Save BACKGROUND: More and more emerging repair materials are used for the repair of skull defects, and it is not clear which repair material is the best choice.  OBJECTIVE: To preliminarily compare the application of three-dimensional digital shaping polyether ether ketone and titanium mesh in skull repair.  METHODS: The clinical data of 174 patients who underwent skull repair in the Department of Neurosurgery of First Affiliated Hospital of Zhengzhou University from January 2017 to September 2020 were analyzed retrospectively. There were 126 males and 48 females with an average age of (43.9±12.0) years. Among them, 95 cases were treated with polyether ether ketone repair materials and 79 cases with titanium mesh. The intraoperative data, postoperative complications and follow-up results (including seizures, hematoma which requiring surgical treatment, infection, subcutaneous effusion, cerebrospinal fluid leakage, loosening or depression of repair materials, exposure of implants, and subjective feelings) were obtained. The differences between the two groups were compared. The protocol was in accordance with the requirements of the Ethics Committee of First Affiliated Hospital of Zhengzhou University. RESULTS AND CONCLUSION: (1) The postoperative follow-up time was from 2 to 37 months, and the average follow-up time was (17.2±12.4) months in 174 patients. (2) The total incidence of postoperative complications in the polyether ether ketone group and the titanium mesh group was 20% and 26%, respectively, and there was no significant difference between the two groups (P > 0.05). (3) There was no significant difference in epilepsy, hematoma, surgical site infection, subcutaneous effusion, cerebrospinal fluid leakage, loosening or depression of repair materials between the two groups (P > 0.05). There was no significant difference in proportion of bilateral symmetry of head between the two groups (P > 0.05). Occurrence ratios of exposure of repair materials, vibration sensation, hot and cold experience were lower in the polyether ether ketone group than those in the titanium mesh group (P < 0.05). (4) Both the polyether ether ketone and the titanium mesh have good bioaffinity. The exposure of repair materials and the experience of vibration and hot and cold sensation in the polyether ether ketone group are better than those in the titanium mesh group.   Figures and Tables | References | Related Articles | Metrics

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Application of manganese in biomaterials: current situation and problems Zhang Chang, Yu Zhengwen 2022, 26 (34):  5504-5511.  doi: 10.12307/2022.463 Abstract ( 914 )   PDF (1031KB) ( 108 )   Save BACKGROUND: Metal elements play an important role in the human body. In recent years, the application of metal elements in biomaterials has attracted attention, and its functions and effects are being rapidly explored and broadened. Compared with the metal elements that have been studied more in recent years, such as magnesium and zinc, manganese is a rising star in the field of biomaterials research. OBJECTIVE: To summarize and review application status and existing problems of manganese in biomaterials.  METHODS: The first author searched CNKI, Wanfang, ScienceDirect, and PubMed databases by computer to retrieve all relevant articles published from February 2010 to February 2021. The Chinese search terms were “manganese, biomaterials, biomedical metallic materials, ceramic biomaterial, nanomaterial, biopolymer material, bone tissue engineering, drug delivery, cancer therapy”, and the English search terms were “manganese, biomaterials, alloy, degradable metals, corrosion, biomedical metallic materials, ceramic biomaterial, nanomaterial, biopolymer material, bone tissue engineering, drug delivery, cancer therapy”. Finally, 72 included articles were summarized.  RESULTS AND CONCLUSION: (1) The current research found that the introduction of manganese into biomaterials can significantly improve the mechanical properties and corrosion resistance of biomaterials, and effectively improve the biocompatibility, bone formation and antibacterial properties of biomaterials, indicating that the incorporation of manganese ions as functional ions into biological materials has good research value. (2) The current research on manganese ions in biomaterials mainly focuses on in vivo and in vitro experiments. The existing studies have shown that combining manganese ions with collagen-hydroxyapatite scaffolds can promote osteogenesis of bone marrow mesenchyme stem cells in vitro and regeneration of new bone in mouse skull defects, and further enhance the osteoinductivity. (3) In view of the excellent properties of manganese, it can have broad application prospects in medical metal materials, bone tissue engineering materials, drug delivery, and tumor treatment. It is expected to provide a new direction for the basic and clinical applications of manganese-related biomaterials in the future.  Figures and Tables | References | Related Articles | Metrics

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Clinical application of acellular dermal matrix Zhu Keying, Guo Rong, Chen Dedian, Huang Sheng 2022, 26 (34):  5512-5517.  doi: 10.12307/2022.471 Abstract ( 620 )   PDF (820KB) ( 49 )   Save BACKGROUND: As a skin substitute, acellular dermal matrix has broad prospects and market. OBJECTIVE: To review the clinical application of acellular dermal matrix.  METHODS: The authors searched PubMed, CNKI and Wanfang databases for articles published from 2000 to 2021 with the key words of “acellular dermal matrix, reconstruction/repair/plastic/clinical study” in English and Chinese, separately. Finally, 64 articles were included for review. RESULTS AND CONCLUSION: Acellular dermal matrix, characterized by rapid vascularization, low antigenicity, good histocompatibility and stable physicochemical properties, is a commonly used biological material in operations in the head and neck surgery, breast surgery, burn plastic surgery, gynecology, and urology. The main problem lies in its low output and the complicated production process to meet the medical standards. Thus, the price of acellular dermal matrix used in clinical use is high, increasing the medical economic burden of patients. Although most of the alloantigen substances are removed, acellular dermal matrix is still a foreign material for patients, so there is still a risk of surgical complications, such as rejection and infection. For future acellular dermal matrix, it is necessary to optimize the production process, improve the production process, reduce the production cost and increase the commercial specifications. From improving the decellularization process, it further removes proteins and other allergens from the acellular dermal matrix while preserving the dermal matrix, further reduces the immunogenicity of the acellular dermal matrix, enhances its compatibility, and reduces adverse events, such as infection and rejection. Figures and Tables | References | Related Articles | Metrics

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Advantages and application strategies of hyaluronic acid scaffold in cartilage repair engineering Liu Hui, Liu Aifeng, Zhang Yu, Zhang Chao 2022, 26 (34):  5518-5524.  doi: 10.12307/2022.464 Abstract ( 443 )   PDF (1072KB) ( 61 )   Save BACKGROUND: Due to its easy modification characteristics, how to use various modification methods to obtain a scaffold that meets the requirements of tissue engineering cartilage repair has become the focus of current research. OBJECTIVE: To review characteristics of hyaluronic acid cartilage repair scaffolds modified by various modification methods and their advantages and applications in cartilage tissue engineering. METHODS: A computer search of the articles concerning hyaluronic acid cartilage repair scaffolds on CNKI, Wanfang, VIP, and PubMed databases was conducted from January 2011 to March 2021. The “hyaluronic acid, cartilage, scaffold, tissue engineering” in Chinese and English were used as search terms. Finally, 72 articles were included for analysis. RESULTS AND CONCLUSION: (1) The modifiability of hyaluronic acid provides an important application strategy for efficient and high-quality cartilage repair. At present, many related researches have achieved remarkable results. Carboxyl modified hyaluronic acid scaffolds can improve the survival rate and metabolic activity of seed cells, and have good biocompatibility. Hydroxy modified hyaluronic acid scaffold has good mechanical properties and biodegradability. The acetamino modification of hyaluronic acid was not used for cartilage repair because of the toxicity of the deacetylation reagent. The grafted hyaluronic acid scaffold can repair cartilage and subchondral bone, and up regulate cartilage gene expression. The composite modified hyaluronic acid scaffold has excellent spatial structure, which can regulate the directional differentiation of seed cells and inhibit hypertrophy, and it is a multifunctional scaffold. (2) However, hyaluronic acid based scaffolds still face some objective problems and different challenges in cartilage repair, for example, hyaluronic acid based scaffolds cannot completely regenerate hyaluronic cartilage at present. Most of the researches are in the animal experimental stage, and the number of clinical researches is quite limited. (3) In recent years, the design strategy of cartilage tissue engineering scaffolds has changed to the direction of annexing cartilage and subchondral bone repair. The multifunctional scaffold based on hyaluronic acid will be the key to achieve high-quality cartilage repair in the future.  Figures and Tables | References | Related Articles | Metrics

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Hydrogel-based growth factors and drugs in the treatment of intervertebral disc degeneration: problems and prospects Zhao Yunan, Zhang Haobo, Sun Tao, Yang Xuejun 2022, 26 (34):  5525-5533.  doi: 10.12307/2022.465 Abstract ( 498 )   PDF (957KB) ( 45 )   Save BACKGROUND: The number of patients with low back pain due to intervertebral disc degeneration is increasing year by year. However, both surgical and conservative treatments have their limitations. In recent years, new regenerative therapy using hydrogel as carrier has brought new ideas for the treatment of intervertebral disc degeneration.   OBJECTIVE: To summarize the repair effects of various growth factors and drugs loaded on different types of hydrogels on the early degeneration of intervertebral discs.  METHODS: The articles about intervertebral disc degeneration and regeneration therapy and molecular biology published on PubMed, CNKI, and Wanfang databases were searched by computer. The period was set from January 1999 to May 2021. The search terms were “intervertebral disc, intervertebral disc degeneration, hydrogels, growth factors, chemokines, drugs, regeneration, repair” in Chinese and English. Summary was further conducted after screening out 87 articles.  RESULTS AND CONCLUSION: (1) Natural hydrogel can be gradually degraded in the intervertebral disc tissue to become the matrix of the intervertebral disc tissue or be directly absorbed, which reflects its superior biocompatibility, but it also needs to restore the height of the intervertebral disc in the early stage of the treatment of intervertebral disc degeneration to play a supporting role, thereby restoring the biomechanics of the spine. (2) Currently, there are still many problems that need to be solved urgently in the research of active molecules such as growth factors and drugs using hydrogels as carriers to treat intervertebral disc degeneration, including most of the current research results from animal experiments, how to safely and effectively deliver hydrogel composites into the intervertebral disc, and whether the problem of low back pain in patients can be solved immediately in the early stage of treatment. (3) Composite hydrogels have become an important direction for the future development of the treatment of intervertebral disc degeneration due to their superior biomechanical properties and good biocompatibility. Platelet-rich plasma is also a hotspot for the future treatment of intervertebral disc degeneration due to its rich content of various growth factors. (4) Due to the diversity of its materials and polymerization methods, hydrogels can provide a broader application prospect for tissue engineering and medicine, and various growth factors and drugs carried in different types of hydrogels can provide a new idea of great significance in the repair and regeneration treatment of intervertebral disc degeneration. Figures and Tables | References | Related Articles | Metrics

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Nano materials of protein-carrying nanosystems for endosome/lysosome escape: research status and future Mao Yilin, Zhu Zhou, Wang Jian 2022, 26 (34):  5534-5542.  doi: 10.12307/2022.466 Abstract ( 613 )   PDF (1113KB) ( 59 )   Save BACKGROUND: How to effectively transport the extracellular proteins into cells has always been a concern. With the development of nanometer protein carrying technology, efficient protein delivery has been achieved. However, the protein-carrying nanosystem is still largely unable to avoid degradation after entering the endosome/lysosome. Therefore, the utility of the protein can be impeded. OBJECTIVE: To review the progresses of protein-carrying nanosystems promoting endosome/lysosome escape in recent years, to analyze research status and application prospects of nano materials of the protein-carrying nanosystems that promote endosome/lysosome escape. METHODS: The articles published from 2000 to 2021 were retrieved from Web of Science, PubMed, CNKI database and Wanfang database. The Chinese and English search terms were “endosome escape, lysosomal escape, nanoparticles, protein delivery”. All articles were preliminarily eliminated according to the inclusion and exclusion criteria. Finally, 89 articles were included for this review. According to the characteristics of the escape mechanism of endosomes and lysosomes, the functional characteristics and clinical applications of inorganic-organic materials, inorganic materials, organic materials, and bio-related materials were summarized.  RESULTS AND CONCLUSION: (1) The intracellular endosome/lysosome escape of proteins delivered by nano materials as carriers is related to a variety of mechanisms, including proton sponge effect, membrane instability, membrane fusion and other related mechanisms. Through the above mechanisms, the protein-carrying nanosystems can be successfully transferred into the cytoplasm and perform their functions well. (2) There are four types of nano materials by far the most often used to promote the protein-carrying nanosystems to escape from lysosome or endosome: organic-inorganic hybrid materials, inorganic nano materials, nanometer materials and biological organic related nanomaterials. These materials have advantages, such as the good biocompatibility and biodegradability, novel design, customizability, and pH-response. These preliminarily outstanding advantages have been demonstrated in the clinical fields of killing tumors, gene editing, and reducing blood sugar. (3) To further expand the clinical application of protein-carrying nanosystems with the effect of endosome/lysosome escape, detailed studies on nano safety and mechanism researches should not be neglected.  Figures and Tables | References | Related Articles | Metrics

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Effect of crown restoration and crown prosthesis on periodontal tissue and periodontal biomarkers Zhang Jing, Zhang Zhao 2022, 26 (34):  5543-5552.  doi: 10.12307/2022.467 Abstract ( 372 )   PDF (1337KB) ( 40 )   Save BACKGROUND: As a common dental material for repairing tooth defects, crown prosthesis has an influence on the oral periodontium, especially the microecological environment in gingival crevicular fluid, which may be represented by the change of some biomarkers in gingival crevicular fluid. OBJECTIVE: By analyzing causes and research progress on application of periodontal biomarkers affected by crown restoration, the effect was evaluated, and the influence of crown restoration on periodontal tissue was revealed microcosmically, in order to guide the selection of crown restoration in clinical practice. METHODS: We searched relevant articles included in CNKI, Wanfang Data, Chinese Science and Technology Journal Database, and PubMed database with the keywords of “Crown restoration; Gingival crevicular fluid; Periodontal; Inflammation; Biomarker” in Chinese and English, and 63 articles were included for summary. RESULTS AND CONCLUSION: (1) The periodontal tissue can be affected by different materials, crown edge tightness and preparation form, crown edge position, axial plane morphology and other aspects. (2) The biomarkers involved in periodontium affected by crown restoration include bacteria, inflammatory mediators, enzymes, and bone resorption biomarkers. (3) After crown restoration, the increased levels of Streptococcus mutans, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, interleukin 1, interleukin 6, tumor necrosis factor α, aspartate transferase, alkaline phosphatase, matrix metalloproteinase 8, and nuclear factor kappa B receptor activator ligand/osteoprotegerin in the gingival crevicular fluid can indicate the inflammatory state of periodontal tissue. The dynamic monitoring of these biomarkers is helpful to evaluate the adaptability of crown restoration to periodontal tissue, so as to provide clinical convenience for the reasonable application of crown restoration.   Figures and Tables | References | Related Articles | Metrics

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Alternative strategies for tissue engineering repair of meniscus injury Du Chaozheng, Zhi Jiajia, Wang Yue, Wang Xinjun, Yuan Yinpeng, Wang Yuze 2022, 26 (34):  5553-5561.  doi: 10.12307/2022.468 Abstract ( 533 )   PDF (975KB) ( 31 )   Save BACKGROUND: Current surgical methods do not provide a long-term solution for meniscus regeneration and replacement, but tissue engineering techniques can provide alternative therapeutic strategies. OBJECTIVE: To review the clinical strategy and tissue engineering research status of meniscus injury repair. METHODS:  The literature collected on PubMed database, Medline database, Google academic database, CNKI, and Wanfang was searched by computer. Keywords were “meniscus injury; tissue engineering; meta-analysis; allografts; meniscus repair; scaffold; polymers; hydrogels; polyurethane; intestinal submucosa; polycaprolactone; polylactic; self-assembly; bone marrow MSC; meniscus derived stem cells; synovium derived MSCs; adipose derived MSC; co-culture; growth factor; transforming growth factor beta; basic fibroblast growth factor; insulin growth factor” in English, and “meniscus; mesenchymal stem cells; scaffold; growth factor; tissue engineering; compression modulus; tensile modulus; hydrogels; electrospinning” in Chinese. Retrieval period was from January 1, 2005 to October 1, 2020.  RESULTS AND CONCLUSION: As a hot research direction of meniscus treatment, meniscus tissue engineering has achieved abundant research results in all aspects, but there is a lack of a large number of long-term clinical trials to verify the accuracy of the conclusions. Biomolecules are indispensable tools in tissue engineering. At present, more human or animal experiments are needed to determine the exact action signal pathway of different biomolecules, the optimal concentration and combination mode of application, and the delivery mode of biomolecules. Although many kinds of stem cells with the phenotypic differentiation potential of meniscus have been found, the role of various stem cells in tissue engineering is still to be further studied, and the most dominant stem cell type or most suitable for meniscus tissue engineering is still controversial. Simultaneously, meniscus is similar to articular cartilage and intervertebral disc in terms of cell composition, extracellular matrix composition and biomechanical properties, and the repair and regeneration strategies of articular cartilage and intervertebral disc have also attracted much attention. Research progress in similar fields can learn from each other and promote each other. Figures and Tables | References | Related Articles | Metrics

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Understanding of periodontal biomaterials based on the concept of bone homeostasis control and the effects on bone formation Li Maoxue, Ding Yi, Guo Shujuan 2022, 26 (34):  5562-5568.  doi: 10.12307/2022.469 Abstract ( 434 )   PDF (908KB) ( 41 )   Save BACKGROUND: Periodontitis is one of main diseases that cause destruction of alveolar bone and tooth loss in adults. To improve the regeneration effect, regulating bone homeostasis in periodontal tissue through modifying controllable properties of materials can effectively improve the effect of alveolar bone regeneration, which provides a popular development direction of periodontal biomaterials. OBJECTIVE: To summarize the current research status of local bone homeostasis imbalance in periodontitis and periodontal biomaterial modification strategies based on the concept of regulating bone homeostasis, and to discuss the prospects and challenges of current strategies in periodontal regeneration. METHODS: The articles were searched on Web of Science, PubMed, CNKI, and Wanfang databases. The Chinese and English key words were “bone, periodontal tissue, homeostasis, biomaterials, regeneration”. The publication time was limited from January 2000 to December 2020. The articles that were associated with the review content were selected according to the topic. Sixty-one articles were included for the final analysis after excluding the articles that were not related to the content of the article. RESULTS AND CONCLUSION: (1) Oral microflora, its products and inflammation destroy the dynamic balance of osteogenesis and osteoclast metabolism in the periodontal tissue. (2) Physical and chemical properties of biomaterials may affect the dynamic balance of bone homeostasis of periodontal tissue. Therefore, the local bone homeostasis can be adjusted by changing the physical and chemical properties of the material. The main methods include: modifying the physical properties of the material, transmitting biological activity, adjusting inflammatory response, and inhibiting osteoclast production. (3) The concept of regulating bone homeostasis is applied to the development of periodontal biomaterials, which improves the osteogenic effect of periodontal biomaterials, and promotes the development of periodontal tissue engineering materials and clinical periodontal regeneration.  Figures and Tables | References | Related Articles | Metrics

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Advantages and potential of bionic hydrogels in cartilage tissue engineering Hou Yuxi, Zhang Ran, Wu Xiuping, Zhang Qingmei, Li Bing 2022, 26 (34):  5569-5576.  doi: 10.12307/2022.470 Abstract ( 683 )   PDF (1028KB) ( 55 )   Save BACKGROUND: Hydrogels are a kind of elastic biomaterials with smooth surfaces and high water contents, which are expected to be candidates for cartilage regeneration. OBJECTIVE: To review the latest research achievements and the progress of bionic hydrogels in cartilage tissue engineering. METHODS: Articles published between 1986 and 2021 in the Web of Science and PubMed databases were searched by the first author with the key words “hydrogel, cartilage regeneration, cartilage defect, cartilage tissue engineering”. A total of 3 665 articles were primarily examined, and 86 articles were analyzed and summarized after screening. RESULTS AND CONCLUSION: (1) Bionic hydrogel is used for synthesizing biomimetic natural polymer hydrogels, including protein-based materials (such as gelatin, collagen and silk fibroin) and polysaccharide materials (such as hyaluronic acid, chitosan and alginate). Synthetic polymers contain poly(vinyl alcohol), polyethylene glycol, polylactic acid and poly lactide-glycolide copolymer. These materials have their own advantages and disadvantages. Through cross-linking, bionic hydrogels can be synthesized with more advantages, avoiding the shortage of some raw materials. (2) At the present stage, the bionic hydrogel materials studied have their own advantages and disadvantages. For example, the ultraviolet crosslinked chondroitin sulfate and polyethylene glycol material has certain anti-inflammatory properties and can also promote cartilage tissue regeneration, but its ability to promote the proliferation and maturation of chondrocytes needs to be strengthened. The gelatin-hydroxyapatite material prepared by ultraviolet crosslinking has high cell inoculation efficiency and excellent biocompatibility. However, no experiments have been performed to inoculated human bone marrow mesenchymal stem cells on it for experimental observation, and the experimental environment is not complex enough and the observation period is short, which still needs further verification. Polyethylene glycol-dimethacrylic acid can promote the formation of cartilage matrix with a wide range of compression modulus, but it also has some side effects in the process of improving the formation of cartilage matrix. (3) To sum up, bionic hydrogel is a new material with great advantages and potential applications. There do not exist perfect biomimetic hydrogel materials that can be applied for cartilage defects in clinic. Biomimetic hydrogel materials with more complete properties need to be further studied in the future. Figures and Tables | References | Related Articles | Metrics