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    18 November 2026, Volume 30 Issue 32 Previous Issue    Next Issue
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    Performance of calcium sulfate-magnesium oxide composites as anti-infective bone graft materials
    Hu Liqun, Xiao Dongqin, Ma Chenxi, Li Zhuohan, Yan Jiyuan, Li Zhong, He Kui, Duan Ke
    2026, 30 (32):  8309-8318.  doi: 10.12307/2026.207
    Abstract ( 23 )   PDF (12037KB) ( 17 )   Save
    BACKGROUND: Calcium sulfate bone graft materials have good biocompatibility but lack antibacterial properties, potentially leading to infections. Magnesium oxide has antibacterial effects and can promote bone regeneration and angiogenesis. 
    OBJECTIVE: To develop novel calcium sulfate-magnesium oxide bone graft materials with antibacterial properties and the ability to promote bone regeneration, and to systematically evaluate its antibacterial capabilities, cytocompatibility, and osteogenic and angiogenic potential.
    METHODS: (1) α-Calcium sulfate hemihydrate was synthesized by a hydrothermal method. α-Calcium sulfate hemihydrate was mixed with magnesium oxide at mass ratios of 2.5%, 7.5%, 15%, and 25%, respectively. Distilled water was added to the mixture and solidified to form calcium sulfate-magnesium oxide composites, designated CS-2.5MgO, CS-7.5MgO, CS-15MgO, and CS-25MgO, respectively. The surface morphology, compressive strength, in vitro degradation, and H2O2 production in PBS of α-calcium sulfate hemihydrate, CS-2.5MgO, CS-7.5MgO, CS-15MgO, and CS-25MgO were characterized. (2) Escherichia coli (or Staphylococcus aureus) cultures were co-cultured with the five composites. The antibacterial properties of the composites were evaluated by agar plate spread assay and inhibition zone assay. (3) MC3T3 cells were co-cultured with extracts from the five composites. The cytocompatibility of the composites was evaluated by CCK-8 assay and live-dead staining. MC3T3 cells were co-cultured with extracts from the five groups of materials. After osteogenic induction, the osteogenic mineralization-inducing ability of the materials was assessed by alkaline phosphatase and alizarin red staining. RUNX2 and WNT3a protein expression in the cells was detected by western blot assay. (4) Human umbilical vein endothelial cells were co-cultured with extracts from the five groups of materials. The angiogenesis-promoting ability of the materials was assessed by Matrigel tubule formation assay. Endothelial nitric oxide synthase protein expression in the cells was detected by western blot assay. (5) α-Calcium sulfate hemihydrate, CS-2.5MgO, CS-7.5MgO, CS-15MgO, and CS-25MgO containing Staphylococcus aureus were implanted into the muscle incision of SD rats. 1, 3, and 7 days after surgery, the materials and adjacent muscle tissue were rinsed, and the rinsate was collected. Colony formation was assessed by agar plate spread assay. Hematoxylin-eosin staining was performed to determine inflammatory cell infiltration in the muscle tissue surrounding the materials.
    RESULTS AND CONCLUSION: (1) Scanning electron microscopy revealed that α-calcium sulfate hemihydrate was mostly short rod-shaped crystals, with a small number of elongated crystals and smooth surfaces. In the calcium sulfate-magnesium oxide composite, magnesium oxide particle aggregates were distributed on the crystal surfaces and between crystals, and the particle density increased with increasing magnesium oxide content. Compared with α-calcium sulfate hemihydrate, the compressive strength and degradation rate of the calcium sulfate-magnesium oxide composite decreased, while H₂O₂ production increased when immersed in PBS. Agar plate spread assays and inhibition zone assays demonstrated that the calcium sulfate-magnesium oxide composite exhibited excellent antibacterial properties, which increased with increasing magnesium oxide content. CCK-8 assay and live-dead staining demonstrated that α-calcium sulfate hemihydrate, CS-2.5MgO, and CS-7.5MgO exhibited good cytocompatibility. Alkaline phosphatase staining, Alizarin red staining, and western blot assay revealed that the CS-2.5MgO composite exhibited enhanced bone mineralization induction. Matrigel tubule formation assay and western blot assay showed that the CS-7.5MgO group exhibited the strongest angiogenesis ability. (2) Fluid agar plate spread assays revealed that the calcium sulfate-magnesium oxide composite material exhibited superior in vivo antibacterial properties compared with α-calcium sulfate hemihydrate, with this antibacterial activity increasing with increasing magnesium oxide content. Hematoxylin-eosin staining revealed significantly reduced inflammatory cell infiltration and exudation in muscle tissue in all calcium sulfate-magnesium oxide composite groups compared with the α-calcium sulfate hemihydrate group. (3) These results demonstrate that the calcium sulfate-magnesium oxide composite material exhibits excellent cytocompatibility and antibacterial properties, effectively promoting osteogenesis and angiogenesis. 
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    Mechanism by which magnesium implant-activated integrin α10β1 promotes osteogenic differentiation of periosteal stem cells
    Yang Yanjun, Zhu Lin, Gu Yongchun, Yan Zhanjun
    2026, 30 (32):  8319-8326.  doi: 10.12307/2026.456
    Abstract ( 18 )   PDF (2750KB) ( 6 )   Save
    BACKGROUND: Periosteal stem cells are the key cellular population in magnesium-induced osteogenesis. Integrin α10β1 is a magnesium-dependent heterodimeric adhesion molecule. Mg²⁺ binds to the MIDAS domain of integrin α10β1, functioning as a molecular switch to regulate downstream biological processes. 
    OBJECTIVE: To elucidate the mechanism by which magnesium-based implants regulate osteogenic differentiation of periosteal stem cells by activating integrin α10β1. 
    METHODS: Forty-two C57BL/6 mice were randomly divided into a titanium rod implantation group (n=21) and a magnesium rod implantation group (n=21). Titanium rods and magnesium rods were implanted into the medullary cavity of the intercondylar fossa of the left knee joint femur, respectively. Three days post-surgery, samples were collected for TUNEL staining to observe cell apoptosis around the implants. EdU staining was utilized to observe cell proliferation activity in the cortical bone thickening area. Fourteen days post-surgery, samples were collected for Micro-CT analysis of cortical bone thickening and osteogenesis. Hematoxylin-eosin staining was applied to observe the morphology and structure of newly formed bone in the cortical bone thickening area. Calcein green fluorescent double staining was employed to analyze the osteogenic differentiation of periosteal stem cells. qPCR was used to detect the expression of osteogenic marker genes Runx2, osteoblast-specific transcription factor, alkaline phosphatase, osteopontin, and integrin α10 and integrin β1. Western blot assay was utilized to detect the expression of integrin α10, integrin β1, focal adhesion kinase and phosphorylated focal adhesion kinase proteins. Transcriptome sequencing was applied to analyze the expression of Wnt/β-catenin and mitogen-activated protein kinase signaling pathways and the correlation between integrin α10β1 and osteogenic gene expression. 
    RESULTS AND CONCLUSION: (1) TUNEL staining and EdU staining showed a significant accumulation of apoptotic cells around the titanium rods, with only a few proliferating cells observed in the periosteum and no osteogenic differentiation. In contrast, no apoptotic cells were found around the magnesium rods, and a marked increase in proliferating cells was observed in the thickened periosteal region. (2) Micro-CT analysis revealed that the titanium rods did not degrade, while the magnesium rods showed significant degradation. The magnesium rod implantation group exhibited superior cortical bone thickening and osteogenesis compared with the titanium rod implantation group. Hematoxylin-eosin staining and calcein green fluorescence double staining further confirmed that osteogenesis was more pronounced in the magnesium rod implantation group. qPCR results indicated that the mRNA expression of Runx2, osteoblast-specific transcription factors, alkaline phosphatase, osteopontin, integrin α10, and integrin β1 was higher in the magnesium rod implantation group compared with the titanium rod implantation group. Western blot results showed higher expression of integrin α10, integrin β1, focal adhesion kinase (FAK), phosphorylated focal adhesion kinase, and Wnt/β-catenin in the magnesium rod implantation group, whereas mitogen-activated protein kinase (MAPK) expression was lower than in the titanium rod implantation group. Transcriptome sequencing analysis revealed a significant positive correlation between integrin α10β1 and the expression of Runx2, osteoblast-specific transcription factors, alkaline phosphatase, and osteopontin. (3) Conclusion: The results suggest that magnesium-based implants promote osteogenic differentiation of periosteal stem cells by activating the integrin α10β1-focal adhesion kinase/phosphorylated focal adhesion kinase signaling pathway. This activation upregulates Wnt/β-catenin signaling and inhibits certain MAPK signaling pathways, thus facilitating osteogenesis.
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    Mechanical and fluid dynamic characteristics of S-type triply periodic minimal surface radial functionally graded bone scaffolds
    Jia Xianghong, Xu Yan, Zhang Xujing
    2026, 30 (32):  8327-8334.  doi: 10.12307/2026.460
    Abstract ( 21 )   PDF (3354KB) ( 6 )   Save
    BACKGROUND: The biomimetic design and functional gradient regulation of bone scaffolds are key to improving the efficacy of bone defect repair. Currently, homogeneous scaffolds struggle to balance mechanical load-bearing and material transport, often leading to stress concentration or inadequate nutrient supply after implantation, thus limiting bone regeneration outcomes.
    OBJECTIVE: To investigate the differences in mechanical performance, mass transport capacity, and cellular microenvironment construction among Primitive (P-type), Gyroid (G-type), and GP composite scaffold structures.
    METHODS: Based on digital light processing and triply periodic minimal surface theory, a Sigmoid function-driven topological gradient algorithm was proposed to fabricate β-calcium silicate/bioglass radially graded scaffolds with single G-type structure, single P-type structure, and GP type composite structure. The performance of the three types of scaffolds was systematically compared through mechanical simulation, fluid dynamics simulation, and wall shear stress analysis.
    RESULTS AND CONCLUSION: (1) Finite element analysis showed that the G-type structure scaffold had a uniform stress distribution and the highest maximum Mises stress, while the GP-type composite structure scaffold had the lowest maximum Mises stress and a more uniform stress distribution than the single-structure scaffolds. The P-type structure scaffold had the largest maximum displacement, while the GP-type composite structure scaffold had the smallest maximum displacement. Static compression test results showed that the elastic moduli of the G-type, P-type, and GP-type composite structure scaffolds were 2.90, 3.39, and 3.38 GPa, respectively. Fluid dynamics simulation and permeability tests showed that the permeability of the GP-type composite structure scaffold was 3.4 × 10⁻⁹ m², significantly higher than that of the single-structure scaffolds, and within the optimal range of cancellous bone permeability. The average wall shear stress of the G-type structure scaffold was 0.86 Pa, with a maximum of 1.13 Pa; the average wall shear stress of the P-type structure scaffold was 1.40 Pa, with a maximum of 2.65 Pa; and the average wall shear stress of the GP-type composite structure scaffold was 1.01 Pa, with a maximum of 1.68 Pa, which is within the optimal range for bone regeneration stimulation. (2) The results indicate that the GP-type composite structure scaffold, designed with a biomimetic Haversian system gradient, can effectively balance mechanical support and biological function.
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    Effectiveness of collagen and fibrin sealant in repairing articular cartilage damage in rabbits
    Yan Yanliuxing, Deng Xinxin, Zou Jie, Li Jianmo
    2026, 30 (32):  8335-8344.  doi: 10.12307/2026.417
    Abstract ( 22 )   PDF (2783KB) ( 11 )   Save
    BACKGROUND: Articular cartilage is primarily composed of collagen. Using collagen as a scaffold material,  combined with autologous bone marrow mesenchymal stem cells for in situ repair, has become a new method for treating articular cartilage damage.
    OBJECTIVE: To evaluate the effectiveness of collagen combined with fibrin sealant in repairing articular cartilage defects in rabbits.
    METHODS: Forty-eight New Zealand rabbits were used. Full-thickness cartilage defects of 4.5 mm in diameter and 3 mm in depth were created on the trochlear surface of the medial femoral condyle of the left hind limbs. The rabbits were randomly divided into four groups: microfracture group (n=12) underwent microfracture surgery. Collagen group (n=12) underwent microfracture surgery followed by injection of domestically produced collagen into the cartilage defect. CartiRegen group (n=12) underwent microfracture surgery followed by injection of a mixture of imported collagen and fibrin sealant into the cartilage defect. Experimental group (n=12) underwent microfracture surgery followed by injection of a mixture of domestically produced collagen and fibrin sealant into the cartilage defect. At 12 and 24 weeks post-surgery, knee joint MRI examinations were performed, and the knee joint cartilage repair tissue was subjected to hematoxylin-eosin, toluidine blue, safranin O-fast green staining, type II collagen immunohistochemical staining, ICRS scoring, and Mankin scoring. The compression modulus and hardness of the knee joint cartilage repair tissue were measured at 24 weeks post-surgery.
    RESULTS AND CONCLUSION: (1) MRI examinations showed that at 24 weeks post-surgery, the cartilage defect in the microfracture group was almost completely filled, but the integration of the cartilage repair tissue with the surrounding normal cartilage tissue was poor. The cartilage defect in the collagen group was almost completely filled, and the integration with the surrounding normal cartilage tissue was almost complete, with slight differences. The cartilage defects in the CartiRegen group and the experimental group were completely filled, and there were no significant differences in integration and surface level compared with the surrounding healthy cartilage tissue. (2) Histological staining showed that the cartilage tissue in the microfracture group was lightly and unevenly stained, with poor cartilage morphology. The cartilage tissue in the collagen group was more evenly stained, with a smooth cartilage repair surface and good integration with the surrounding normal cartilage tissue, but with some fissures. The cartilage tissue in the CartiRegen group and the experimental group showed uniform staining, a smooth surface, dense tissue, good integration with the surrounding tissue, and good filling. (3) The ICRS score and Mankin score of cartilage repair at 24 weeks post-operation in the CartiRegen group and the experimental group were lower than those in the microfracture group and the collagen group (P < 0.05), and the cartilage hardness at 24 weeks post-operation in the collagen group, CartiRegen group, and experimental group was greater than that in the microfracture group (P < 0.05). (4) The results exhibit that the combination of collagen and fibrin sealant with microfracture surgery has a good repair effect on cartilage damage.

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    Mechanism by which polyetheretherketone, a novel oral restorative material, promotes the proliferation of dental pulp stem cells
    Wu Lin, Lu Tong
    2026, 30 (32):  8345-8351.  doi: 10.12307/2026.885
    Abstract ( 13 )   PDF (3193KB) ( 12 )   Save
    BACKGROUND: Polyetheretherketone, as a novel pulp capping material used in vital pulp therapy, can synergistically regulate the proliferation of dental pulp stem cells through its surface characteristics and released active components, but the specific mechanism remains unclear.
    OBJECTIVE: To investigate the effect of polyetheretherketone on the proliferation of dental pulp stem cells and the related mechanisms.
    METHODS: (1) Human dental pulp stem cells were isolated and cultured. Human dental pulp stem cells were cultured with different mass concentrations of polyetheretherketone [0 (control), 0.1, 1, 10 mg/mL] for 48 hours. Cell proliferation was detected by EdU staining and CCK-8 assay. The expression of extracellular signal-regulated kinase and phosphorylated extracellular signal-regulated kinase proteins was detected by western blot assay. Human dental pulp stem cells were cultured with 1 mg/mL polyetheretherketone for 0, 24, 48, 72, 96, and 120 hours. Cell proliferation was detected by CCK-8 assay. Human dental pulp stem cells were cultured with 0 (control) and 1 mg/mL polyetheretherketone for 48 hours. Cell cycle was detected by flow cytometry. (2) Human dental pulp stem cells were divided into three groups: control group (no intervention), polyetheretherketone group (1 mg/mL polyetheretherketone), and polyetheretherketone+U0126 group (1 mg/mL polyetheretherketone and 10 µmol/L extracellular signal-regulated kinase inhibitor U0126). After 48 hours of culture, cell proliferation was detected by EdU staining and CCK-8 assay. Cell cycle was detected by flow cytometry. The protein expression of extracellular signal-regulated kinase and phosphorylated extracellular signal-regulated kinase was detected by western blot assay. 
    RESULTS AND CONCLUSION: (1) The cell proliferation in the 1 mg/mL polyetheretherketone group was faster than that in the other three groups, and the expression of phosphorylated extracellular signal-regulated kinase protein was higher than that in the control group and the 0.1 mg/mL polyetheretherketone group. Therefore, 1 mg/mL polyetheretherketone was selected for subsequent experiments. Cell proliferation after 96 hours of culture with 1 mg/mL polyetheretherketone was faster than that after 24, 48, and 72 hours. The proportion of cells in the G0/G1 phase in the 1 mg/mL polyetheretherketone group was lower than that in the control group, and the proportion of cells in the S phase was higher than that in the control group. (2) Cell proliferation in the polyetheretherketone group was faster than that in the control group and the polyetheretherketone+U0126 group. The proportion of cells in the G0/G1 phase was lower in the polyetheretherketone group than in the control group and the polyetheretherketone+U0126 group, while the proportion of cells in the S phase and the expression of phosphorylated extracellular signal-regulated kinase protein were higher in the polyetheretherketone group than in the control group and the polyetheretherketone+U0126 group. (3) The results indicate that polyetheretherketone promotes dental pulp stem cell proliferation by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathway.
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    Cyclic fatigue resistance of heat-treated nickel-titanium files in simulated S-shaped root canals at different temperatures
    Fu Hongyu, Chen Wenxin, Hou Xiaomei
    2026, 30 (32):  8352-8357.  doi: 10.12307/2026.884
    Abstract ( 19 )   PDF (1416KB) ( 6 )   Save
    BACKGROUND: Heat-treated nickel-titanium files have gradually become the mainstream instruments in clinical applications due to their excellent flexibility and good root canal shaping ability. However, root canal preparation of S-shaped curved root canals is a challenging aspect of clinical root canal treatment, and instrument separation is prone to occur in complex root canals.
    OBJECTIVE: To compare the cyclic fatigue resistance of five heat-treated nickel-titanium files in simulated S-shaped root canals at different temperatures. 
    METHODS: Twenty samples each of Hyflex CM, M3, Plex, Hyflex EDM, and R-phase nickel-titanium files were selected. A double-curved metal simulated S-shaped root canal was used. The cyclic fatigue resistance of the five types of nickel-titanium files was tested at room temperature (24 °C) and at 65 °C using a heating device. Ten samples of each type of nickel-titanium file were tested at each temperature. The number of cyclic fatigue and the fragment length were recorded. The fragment surfaces of the nickel-titanium files were observed and analyzed in detail using a scanning electron microscope.
    RESULTS AND CONCLUSION: (1) At both temperatures, the five types of nickel-titanium files showed similar fragment patterns in the S-shaped root canal: fragment first occurred in the apical curvature region, followed by fragment at the coronal curvature. The fragment surfaces of all five groups of nickel-titanium files showed typical cyclic fatigue characteristics under scanning electron microscopy. (2) Results at room temperature: The Hyflex EDM group showed the highest number of cyclic fatigue in the apical segment, while the Plex group showed the lowest. The Hyflex CM group showed the highest number of cyclic fatigue in the coronal segment, while the M3 group showed the lowest. The TF group had the longest apical fragment length, while the Hyflex EDM group had the shortest. The Plex group had the longest coronal fragment length, while the Hyflex CM group had the shortest. (3) Results at 65 °C: The TF group showed the highest number of cyclic fatigue in the apical segment, while the M3 group showed the lowest. The Hyflex EDM group showed the highest number of cyclic fatigue in the coronal segment, while the Plex group showed the lowest. The Plex group had the longest apical fragment length, while the M3 group had the shortest. The Hyflex CM group had the longest coronal fragment length, while the Plex group had the shortest. (4) When the temperature increased to 65 °C, except for the TF group, the cyclic fatigue values of the other four nickel-titanium file groups in both the apical and coronal segments were significantly lower than the values measured at room temperature. With increasing temperature, the apical fragment lengths of the Hyflex CM, Plex, and Hyflex EDM groups showed an increasing trend, and the coronal fragment lengths of the Hyflex CM and M3 groups also showed an increasing trend. The results indicate that, at room temperature and under heating, the Hyflex EDM nickel-titanium file and the R-phase nickel-titanium file TF exhibited superior cyclic fatigue resistance in S-shaped simulated root canals. Heating to 65 °C may reduce the cyclic fatigue resistance of Hyflex CM and Hyflex EDM nickel-titanium files.
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    Effects of different methods for removing invisible orthodontic resin attachments on the enamel surface
    Yu Yongyue, Liu Mingxin, Lu Yun, Gao Lu, Wu Dalei
    2026, 30 (32):  8358-8363.  doi: 10.12307/2025.875
    Abstract ( 14 )   PDF (1493KB) ( 6 )   Save
    BACKGROUND: In recent years, invisible orthodontic technology has been widely adopted by most orthodontic patients. However, improper removal of invisible orthodontic resin attachments may lead to permanent enamel damage and increased susceptibility to caries. Therefore, maintaining enamel integrity during the removal of resin attachments is of great importance.
    OBJECTIVE: To investigate the effects of four methods for removing resin attachments on enamel surface morphology, roughness, and resistance to caries.
    METHODS: Sixty-nine healthy premolars requiring extraction for orthodontic treatment were collected, and the crowns were preserved. (1) 60 teeth were randomly selected; the surface of each tooth was divided into five zones, and assigned to one control group (untreated tooth surface) and groups A, B, C, and D. Groups A–D received resin attachments bonded to the tooth surfaces. Group A first removed the resin attachments using a yellow-labeled diamond bur, then polished the tooth surface with Silicone One Gloss silica particles; group B first removed the resin attachments using a tungsten carbide bur, then polished the tooth surface with Silicone One Gloss silica particles; group C first removed the resin attachments using tungsten carbide burrs, then polished the tooth surfaces using EVE Twist cyclone wheels; group D first removed the resin attachments using yellow-labeled diamond bur, then polished the tooth surfaces using EVE Twist cyclone wheels. Tooth surface roughness values were measured before resin attachment bonding (T0), after debonding (T1), and after resin attachment removal and polishing (T2). Scanning electron microscopy was used to observe the enamel surface morphology after polishing. (2) Nine tooth crown samples were selected, and each tooth surface was divided into four sections, corresponding to the control group (untreated tooth surface), and groups A, B, and C. The treatment methods were the same as above. A caries resistance experiment was then conducted for 20 days. After the experiment, scanning electron microscopy was used to observe the demineralization morphology of the enamel surface.
    RESULTS AND CONCLUSION: (1) Intra-group comparison: The tooth surface roughness values of samples in groups A, B, C, and D at T1 were greater than at T0. The tooth surface roughness values of samples in all four groups at T2 were less than at T1. The tooth surface roughness values of samples in groups A, B, and D at T2 were greater than at T0. Intergroup comparison: Comparing the difference in tooth surface roughness between T1 and T0, groups B and C showed smaller differences than groups A and D. Comparing the difference in tooth surface roughness between T2 and T0, group C showed smaller differences than groups A, B, and D. Based on the tooth surface roughness measurements, group D showed significant enamel scratches and was not subjected to scanning electron microscopy observation. Scanning electron microscopy showed that group A had rough scratches and wide grooves on the enamel surface; group B had a rough enamel surface with numerous rough scratches; group C had fine, scattered scratches on the enamel surface. (2) After the anti-caries experiment, scanning electron microscopy showed that the enamel surface of group A was rough and uneven, with demineralization pores visible between calcified clusters; the enamel surface of group B was relatively smooth, and the demineralization pores were significantly smaller than those in group A; the enamel surface of group C was the smoothest, with fine demineralization pores, closer to the enamel surface of the control group. (3) The results show that during the resin attachment removal stage, using tungsten carbide burs caused less damage to the tooth surface and resulted in a smaller decrease in anti-caries ability compared to using diamond burs. During the polishing stage after resin attachment removal, using EVE Twist cyclone wheels caused less damage to the tooth surface and resulted in a smaller decrease in anti-caries ability compared to using silicon particle polishing. 
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    Novel collagen membrane in repairing skull bone defects in rats
    Yang Ping, Qi Xiaoyang, Lei Zhijie, Chen Yixin, Qiu Xusheng
    2026, 30 (32):  8364-8371.  doi: 10.12307/2026.208
    Abstract ( 20 )   PDF (2729KB) ( 5 )   Save
    BACKGROUND: The commonly used absorbable barrier membrane in guided bone regeneration technology is Bio-Gide collagen membrane (source of pig skin), which has the disadvantages of poor mechanical strength and fast degradation rate, thus limiting its clinical application. Therefore, it is of great significance to develop collagen membranes with better physicochemical properties.
    OBJECTIVE: To prepare a novel collagen membrane derived from porcine bladder, characterize its physicochemical properties and its effect on repairing rat skull bone defects. 
    METHODS: (1) The serosal layer and partial muscle layer of porcine bladders were removed to prepare a novel collagen membrane. The surface morphology, water absorption, porosity, degradation rate, tensile modulus, and ultimate load of the novel and Bio-Gide collagen membranes were characterized. (2) Rat bone marrow mesenchymal stem cells were co-cultured with the novel and Bio-Gide collagen membranes, respectively. Cells cultured alone were used as controls. Cell proliferation was assessed by CCK-8 assay. Osteogenic differentiation was assessed by alkaline phosphatase staining 7 days after osteogenic induction. (3) A 5-mm-diameter circular, full-thickness bone defect was created on each side of the sagittal suture of the skull in 18 SD rats. Thirty-six defect sites were randomly divided into six intervention groups: the control group (n=6) received no implantation at the defect site; the Bio-Oss group (n=6) had the defect filled with Bio-Oss bone powder; the Bio-Gide group (n=6) had the defect covered with a Bio-Gide membrane; the novel collagen membrane group (n=6) had the defect covered with a novel collagen membrane; the Bio-Oss+Bio-Gide group (n=6) had the defect filled with Bio-Oss bone powder and then covered with a Bio-Gide membrane; and the Bio-Oss+novel collagen membrane group (n=6) had the defect filled with Bio-Oss bone powder and then covered with a novel collagen membrane. Twelve weeks after surgery, the tissue samples were harvested for micro-computed tomography and histological observation.
    RESULTS AND CONCLUSION: (1) Scanning electron microscopy revealed that the fibers in the compact layers of the Bio-Gide and novel collagen membranes were denser, with the fibers in the Bio-Gide membrane interlaced. The fibers in the novel collagen membrane were denser and connected into sheets. The fibers in the porous layers of both membranes were looser, with the Bio-Gide membrane having more pores. The porosity and water absorption of the novel collagen membrane were lower than those of the Bio-Gide membrane (P < 0.05), while the tensile elastic modulus and ultimate load were higher than those of the Bio-Gide membrane (P < 0.05). (2) Compared with the Bio-Gide membrane, the novel collagen membrane was more stable to degradation. CCK-8 assay showed that both the Bio-Gide and novel collagen membranes promoted the proliferation of rat bone marrow mesenchymal stem cells. Alkaline phosphatase staining revealed that neither the Bio-Gide nor the novel collagen membranes affected the osteogenic differentiation of rat bone marrow mesenchymal stem cells. (3) Micro-computed tomography revealed a small amount of new bone formation at the bone defect site in the control group, while substantial new bone formation was observed in the other five groups. The Bio-Oss+novel collagen membrane group demonstrated the greatest amount of new bone formation and structural maturity. Hematoxylin-eosin and Masson staining revealed less new bone formation at the defect site in the control group, while more was observed in the other five groups. The Bio-Oss+novel collagen membrane group demonstrated higher new bone density and more mature structure. (4) The results demonstrated that the novel collagen membrane exhibited superior physical and chemical properties to the Bio-Gide membrane. When combined with Bio-Oss bone powder, the novel collagen membrane demonstrated superior bone repair efficacy compared with the Bio-Gide membrane.
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    Preparation and properties of biomimetic periosteum of polyvinylidene fluoride doped with zinc and magnesium
    Li Dongyao, Zhao Shuai, Wei Suiyan, Cao Yijing, Xu Guoqiang, Lyu Zelin
    2026, 30 (32):  8372-8377.  doi: 10.12307/2026.887
    Abstract ( 17 )   PDF (1689KB) ( 6 )   Save
    BACKGROUND: In the process of repairing bone defects using guided bone regeneration technology, the barrier membrane needs to prevent surrounding soft tissue from entering the bone defect area while also allowing osteoblasts to preferentially grow into the area. Therefore, researching a barrier membrane with excellent performance is of great significance for the implementation of this technology.
    OBJECTIVE: To prepare zinc-magnesium polyvinylidene fluoride biomimetic periosteum and analyze its performance. 
    METHODS: Polyvinylidene fluoride biomimetic periosteum was prepared using electrospinning technology, including pure polyvinylidene fluoride membranes (denoted as PVDF membranes), polyvinylidene fluoride biomimetic periosteum doped with 1%, 2%, and 3% ZnCl2 (denoted as 1%ZnCl2-PVDF, 2%ZnCl2-PVDF, and 3%ZnCl2-PVDF membranes, respectively), polyvinylidene fluoride biomimetic periosteum doped with 1%, 2%, and 3% MgCl2 (denoted as 1%MgCl2-PVDF, 2%MgCl2-PVDF, and 3%MgCl2-PVDF membranes, respectively), and polyvinylidene fluoride biomimetic periosteum doped with 1%, 2%, and 3% (ZnCl2+MgCl2) [denoted as 1%(ZnCl2+MgCl2)-PVDF, 2%(ZnCl2+MgCl2)-PVDF, and 3%(ZnCl2+MgCl2)-PVDF membranes, respectively]. The microstructure, β-phase content, zinc and magnesium ion release, maximum tensile load, and water contact angle of the polyvinylidene fluoride biomimetic bone membranes were characterized.
    RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that the nanofibers of the 10 groups of periosteum were interwoven to form a network. Among them, the PVDF, 1%ZnCl2-PVDF, 1%MgCl2-PVDF, and 1%(ZnCl2+MgCl2)-PVDF membranes had a uniform texture and relatively consistent fiber diameters. After the bone membranes were immersed in PBS for 14 days, the release of zinc and magnesium ions from the 1%ZnCl2-PVDF, 1%MgCl2-PVDF, and 1%(ZnCl2+MgCl2)-PVDF membranes was relatively stable. Combining microscopic morphology and zinc and magnesium ion release, subsequent tests were conducted on PVDF, 1%ZnCl2-PVDF, 1%MgCl2-PVDF, and 1%(ZnCl2+MgCl2)-PVDF membranes. (2) The addition of 1%ZnCl2 and/or 1%MgCl2 had no significant effect on the β-phase content of the polyvinylidene fluoride biomimetic bone membrane. The PVDF membrane had the lowest maximum tensile load, while the 1%ZnCl2-PVDF membrane had the highest maximum tensile load. The addition of 1%ZnCl2 and/or 1%MgCl2 had no significant effect on the water contact angle of the polyvinylidene fluoride biomimetic periosteum. (3) The results show that the polyvinylidene fluoride biomimetic periosteum doped with 1%ZnCl2 and/or 1%MgCl2 has good surface morphology and mechanical properties.

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    Biomimetic black phosphorus nanosystem regulates synovial macrophage polarization for osteoarthritis treatment
    Yu Cenqi, Liu Yang, Yu Jianfeng, Kang Kang, Deng Yaoge, Xia Xiaowei, Zhang Yijian, Zhu Xuesong
    2026, 30 (32):  8378-8390.  doi: 10.12307/2026.882
    Abstract ( 23 )   PDF (4147KB) ( 7 )   Save
    BACKGROUND: Previous studies have shown that M2 macrophage membrane-modified nanosystems can achieve efficient aggregation in joint and inflammation-related diseases, thereby significantly alleviating inflammation and tissue damage. 
    OBJECTIVE: To investigate the therapeutic effect of M2 macrophage membrane-coated black phosphorus nanosheets (denoted as BPNs) combined with near-infrared photothermal stimulation on osteoarthritis. 
    METHODS: (1) BPNs were synthesized using a modified liquid-phase exfoliation method. The BPNs were then modified with interleukin-4-induced M2 macrophage membranes to obtain M2 macrophage membrane-coated black phosphorus nanosheets (denoted as M2M@BPNs). The microstructure, hydration particle size, and photothermal properties of M2M@BPNs were characterized. (2) Mouse bone marrow macrophages were cultured in five groups. The control group received no treatment. The lipopolysaccharide group was induced to polarize to the M1 type and then cultured in PBS for 24 hours. In the BPNs group and the M2M@BPNs group, after inducing cell polarization towards the M1 type, BPNs and M2M@BPNs were added respectively and the cells were cultured for 24 hours. In the M2M@BPNs+near-infrared intervention group, after inducing cell polarization towards the M1 type, M2M@BPNs were added and the cells were cultured for 24 hours, during which near-infrared light was irradiated for 180 seconds. After culture, cell viability was detected by CCK-8 assay. The expression of CD86, inducible nitric oxide synthase, CD206, and arginase 1 mRNA was detected by RT-qPCR. Immunofluorescence staining was used to detect CD86 expression. (3) The supernatant of mouse bone marrow macrophages was collected from the lipopolysaccharide group, BPNs group, M2M@BPNs group, and M2M@BPNs+near-infrared intervention group. After centrifugation, the supernatant was used as conditioned medium to culture mouse knee chondrocytes, with untreated chondrocytes as controls. After 24 hours of culture, Alcian blue and safranin O staining were utilized to observe extracellular matrix deposition. RT-qPCR was used to detect the mRNA expression of aggrecan, type II collagen, matrix metalloproteinase 13, and integrin-metalloproteinase 5. Immunofluorescence staining was applied to measure the expression of matrix metalloproteinase 13. (4) The above four groups of conditioned mediums were employed to culture mouse embryonic fibroblasts, with untreated fibroblasts as controls. After 24 hours of culture, RT-qPCR was used to examine the mRNA expression of type I collagen, type III collagen, and α-smooth muscle actin. Immunofluorescence staining was used to detect type I collagen expression. Scratch assay was used to detect cell migration. (5) Thirty C57BL/6J mice were randomly divided into five intervention groups: The sham-operated group (n=6) received no modeling. The osteoarthritis group (n=6) underwent medial meniscus and tibial ligament transection to establish an osteoarthritis model, followed by intra-articular injection of PBS one week later. The BPNs group (n=6) and the M2M@BPNs group (n=6) received intra-articular injections of BPNs and M2M@BPNs, respectively, one week after modeling. The M2M@BPNs+near-infrared intervention group received intra-articular injection of M2M@BPNs one week after modeling, followed by near-infrared light irradiation (3 times) 24 hours later, with treatment once a week. Eight weeks post-operation, tissue samples were collected for hematoxylin-eosin staining of articular cartilage and synovial tissue, safranin O-fast green and toluidine blue staining of articular cartilage, CD86 and CD206 immunofluorescence staining of synovial tissue, type II collagen and matrix metalloproteinase 13 immunofluorescence staining of cartilage tissue, and hematoxylin-eosin staining of major organs. 
    RESULTS AND CONCLUSION: (1) M2M@BPNs exhibited an ultrathin nanosheet morphology with an average particle size of (184.76±0.46) nm, stably increasing temperature by 6°C under near-infrared irradiation, and demonstrated good photothermal stability. (2) CCK-8 assays showed that BPNs, M2M@BPNs, and M2M@BPNs+near-infrared intervention did not affect the survival rate of bone marrow macrophages, indicating good cell compatibility. The experimental results showed that M2M@BPNs combined with near-infrared intervention significantly decreased CD86 and inducible nitric oxide synthase expression and increased CD206 and arginase-1 expression, promoting M2 polarization in macrophages. (3) Comprehensive experimental results showed that M2M@BPNs combined with near-infrared conditioned medium could increase the expression of proteoglycans and type II collagen in chondrocytes, decrease the expression of matrix metalloproteinase 13 and integrin-metalloproteinase 5, and promote cartilage formation. M2M@BPNs combined with near-infrared conditioned medium could decrease the expression of type I collagen, type III collagen, and α-smooth muscle actin in fibroblasts, and inhibit fibroblast migration. (4) Comprehensive experimental results showed that M2M@BPNs combined with near-infrared intervention could improve cartilage structure, retain proteoglycans, decrease the expression of CD86 and matrix metalloproteinase 13, increase the expression of CD206 and type II collagen, alleviate synovial hyperplasia and osteoarthritis degeneration, and had good in vivo biocompatibility. (5) The results indicated that M2M@BPNs combined with near-infrared intervention could regulate macrophage polarization, indirectly maintain the homeostasis of chondrocytes and fibroblasts, and thus exert a cartilage-protective effect in osteoarthritis.
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    Oral ginger-derived exosome-like nanoparticles promote sciatic nerve injury repair: efficacy and mechanism
    Su Meijia, Li Hongyu, Liu Qi, Xia Bing, Cai Jing, Huang Jinghui
    2026, 30 (32):  8391-8401.  doi: 10.12307/2026.473
    Abstract ( 19 )   PDF (2860KB) ( 5 )   Save
    BACKGROUND: Plant-derived exosome-like nanoparticles have become a research hotspot in tissue repair due to their natural biocompatibility, low immunogenicity, and rich bioactive components. Among them, ginger-derived exosome-like nanoparticles have shown potential in anti-inflammatory and tissue repair promotion, but their role and mechanism in peripheral nerve regeneration remain unclear.
    OBJECTIVE: To investigate the role and potential mechanism of ginger-derived exosome-like nanoparticles in the repair of sciatic nerve injury.
    METHODS: (1) Ginger-derived exosome-like nanoparticles were isolated from fresh ginger using differential centrifugation combined with sucrose density gradient centrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, BCA protein quantification, Coomassie Brilliant Blue staining, and western blot analysis for plant vesicle markers. (2) Ginger-derived exosome-like nanoparticles suspensions of different mass concentrations (0, 5, 10, and 15 μg/mL) were co-cultured with dorsal root ganglion neurons of newborn mice. β-III tubulin immunofluorescence staining was used to observe neuronal axonal growth and the uptake of ginger-derived exosome-like nanoparticles by neurons. (3) A sciatic nerve crush injury model was established in mice. Ninety-six mice were randomly divided into a model control group and low-, moderate-, and high-dose ginger-derived exosome-like nanoparticle groups (n=24 per group). Assuming the dosage volume was 5 mL/kg, each group was administered ginger-derived exosome-like nanoparticle suspension by gavage at doses of 0, 5, 10, and 15 μg/kg, respectively, once daily for 28 days. Body weight and limb motor function were assessed on days 7, 14, 21, and 28 post-administration. After the last administration, histopathological changes in major organs and relative wet weight of the gastrocnemius muscle were examined. Fluoro-gold retrograde labeling was used to measure dorsal root ganglion axonal regeneration. Transmission electron microscopy was utilized to detect sciatic nerve myelin regeneration. Within 48 hours post-administration, the biodistribution of DiR-labeled ginger-derived exosome-like nanoparticles in mice was dynamically observed using in vivo imaging. Western blot analysis was used to detect the protein expression of growth-associated protein 43 (day 7 post-administration) and neurofilament protein 200 (day 28 post-administration) in the dorsal root ganglion.
    RESULTS AND CONCLUSION: (1) Ginger-derived exosome-like nanoparticles exhibited a particle size distribution peaking at (113.4±35.8) nm and a typical cup-shaped vesicular morphology consistent with exosome characteristics. Western blot analysis confirmed the high purity of ginger-derived exosome-like nanoparticles. (2) Compared with the other three groups, 15 μg/mL ginger-derived exosome-like nanoparticles suspension significantly promoted neurite growth. Ginger-derived exosome-like nanoparticles could be effectively taken up by neurons. (3) Body weight monitoring results showed that different doses of ginger-derived exosome-like nanoparticles did not affect the growth and development of mice. Hematoxylin-eosin staining showed that different doses of ginger-derived exosome-like nanoparticles did not cause significant organ damage in mice, demonstrating good systemic safety. In vivo imaging dynamic observation showed that ginger-derived exosome-like nanoparticles specifically accumulated in the gastrointestinal tract, reaching a peak at 12 hours after administration. The high-dose ginger-derived exosome-like nanoparticle group showed better dorsal root ganglion axon regeneration, sciatic nerve myelin regeneration, and limb motor function than the other three groups. The relative wet weight of the gastrocnemius muscle and the protein expression of growth-related protein 43 and neurofilament protein 200 were also higher than the other three groups. The results confirm that oral administration of ginger-derived exosome-like nanoparticles promoted the regeneration of neural structures and the recovery of function after sciatic nerve injury, demonstrating clear neurorepair activity. This mechanism was closely related to the upregulation of neurofilament protein 200 and growth-associated protein 43 expression.
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    Application of photocrosslinkable nanofiber scaffold loaded with decellularized cartilage matrix in cartilage tissue engineering
    Zhu Jisheng, Teng Jianxiang, Zou Zihao, Pan Jiazhao, Zhou Tianqi, Shu Xiaolin, He Cheng, Yuan Daizhu, Tian Xiaobin
    2026, 30 (32):  8402-8412.  doi: 10.12307/2026.457
    Abstract ( 15 )   PDF (55590KB) ( 6 )   Save
    BACKGROUND: Tissue engineering strategies, particularly those based on decellularized cartilage matrix and biomimetic scaffolds, offer new therapeutic directions for cartilage regeneration. 
    OBJECTIVE: To develop a photocrosslinkable nanofiber scaffold loaded with decellularized cartilage matrix and evaluate its potential for cartilage tissue engineering.
    METHODS: (1) Decellularized cartilage matrix was prepared by enzymatic digestion and a combined chemical-ultrasonic method. A photocrosslinkable polyvinyl alcohol-glycidyl methacrylate polymer was synthesized. 8% polymer solution and 3% decellularized cartilage matrix solution were mixed at volume ratios of 8:1, 4:1, and 2:1 to prepare electrospinning precursor solutions. Nanofiber scaffolds were fabricated using electrospinning technology, designated as PVA-GMA-dECM(8:1), PVA-GMA-dECM(4:1), and PVA-GMA-dECM(2:1), respectively. A polyvinyl alcohol-glycidyl methacrylate nanofiber scaffold (PVA-GMA) was also prepared. The microstructure of each scaffold was characterized. Chondrocytes were co-cultured non-contact with the four types of ultraviolet-irradiated crosslinked scaffolds using Transwell chambers, and cell proliferation was detected by the CCK-8 assay. Based on morphological observations and CCK-8 results, a suitable scaffold was selected for subsequent experiments. (2) The surface water contact angle and maximum tensile stress of PVA-GMA, PVA-GMA-dECM(8:1), and PVA-GMA-dECM(4:1) were measured. Based on these results, a suitable scaffold was selected for further experiments. Chondrocytes were co-cultured non-contact with ultraviolet-irradiated crosslinked PVA-GMA and PVA-GMA-dECM(4:1) using Transwell chambers. EdU staining and live/dead staining were used to assess cell proliferation and viability, and scratch assay and invasion assay were used to evaluate cell migration ability. (3) Using a Transwell chamber, chondrocytes were co-cultured non-contact with ultraviolet-irradiated cross-linked PVA-GMA and PVA-GMA-dECM (4:1). After chondrogenic induction culture, the chondrogenic differentiation efficiency was evaluated by Alcian blue staining, RT-qPCR (detecting type II collagen and Sox9 mRNA expression), immunofluorescence staining (detecting type II collagen and aggrecan expression), and western blot assay (detecting type II collagen and Sox9 protein expression).
    RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that a high proportion of decellularized cartilage matrix (2:1) affected the fiber morphology, while a 4:1 ratio yielded well-structured nanofibers. CCK-8 assay showed that PVA-GMA-dECM promoted ATDC5 chondrocyte proliferation compared with PVA-GMA. Based on the results of these two experiments, PVA-GMA-dECM (2:1) was excluded from subsequent experiments. The water contact angle of PVA-GMA-dECM (4:1) was lower than that of PVA-GMA and PVA-GMA-dECM (8:1), and the maximum tensile strength was greater than that of PVA-GMA and PVA-GMA-dECM (8:1). Therefore, PVA-GMA-dECM (8:1) was excluded from subsequent experiments. Live/dead staining and EdU staining showed that both PVA-GMA and PVA-GMA-dECM (4:1) maintained cell viability, and PVA-GMA-dECM (4:1) had a better cell proliferation effect than PVA-GMA. PVA-GMA-dECM (4:1) had a stronger cell migration ability than PVA-GMA. PVA-GMA-dECM (4:1) had a stronger chondrogenic differentiation efficiency than PVA-GMA. (2) The results show that PVA-GMA-dECM (4:1) exhibits excellent bioactivity and can effectively promote chondrocyte proliferation, migration, and chondrogenic differentiation, making it a promising scaffold material for cartilage tissue engineering.
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    Copper phosphate nanohydrogel dressing promotes skin wound healing in mice
    Fan Xiao, Li Huiyun, Dou Fuguo, Zhang Nan, Zhang Xinyan
    2026, 30 (32):  8413-8419.  doi: 10.12307/2026.879
    Abstract ( 16 )   PDF (3313KB) ( 6 )   Save
    BACKGROUND: In recent years, novel dressings, including hydrogel dressings, have become an emerging research hotspot in the field of skin wound treatment. Studies have confirmed that composite nanomedical materials loaded with copper nanoparticles can effectively promote the expression of vascular endothelial growth factor in wound tissue and promote angiogenesis, increase collagen deposition, and contribute to wound healing.
    OBJECTIVE: To prepare copper phosphate nanohydrogel dressings and analyze their effects on skin wound healing in mice. 
    METHODS: (1) Copper phosphate nanohydrogel dressings were prepared using agar hydrogel as the matrix, and the microstructure of the dressings was observed under a scanning electron microscope. (2) Six KM mice were randomly divided into two groups: the experimental group (n=3) received subcutaneous injection of copper phosphate nanohydrogel dressing, and the control group (n=3) received no injection. Tissue samples were collected 24 hours after injection, and hematoxylin-eosin staining was used to observe pathological changes in the heart, liver, spleen, lungs, and kidneys. (3) Escherichia coli bacterial solution was co-cultured with liquid culture medium (blank group), liquid culture medium + agar hydrogel dressing (hydrogel group), and liquid culture medium + copper phosphate nanohydrogel dressing (copper phosphate nanohydrogel group) for 8 hours. Plate coating experiments were performed to detect bacterial survival rate. (4) Fifteen KM mice were used, and a 1 cm diameter full-thickness skin defect was created on the back of each mouse. The mice were randomly divided into three groups: control group (n=5) treated with povidone-iodine and covered with gauze, hydrogel group (n=5) treated with povidone-iodine and covered with agar hydrogel dressing, and copper phosphate nanohydrogel group (n=5) treated with povidone-iodine and covered with copper phosphate nanohydrogel dressing. The dressings were changed every 3 days, and wound healing was observed. After 7 days of intervention, tissue samples were collected. Masson staining was used to observe collagen deposition (granulation tissue). CD31 immunofluorescence staining was utilized to observe angiogenesis. Western blot assay was applied to detect the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins.
    RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that the copper phosphate nanohydrogel dressing exhibited a porous structure with high porosity and irregular pore sizes, and a sheet-like scaffold structure was visible within the pores. (2) After subcutaneous injection of the copper phosphate nanohydrogel dressing, there were no significant pathological changes in the heart, liver, spleen, lungs, and kidneys of mice. (3) The survival rate of Escherichia coli in the copper phosphate nanohydrogel group was lower than that in the blank group and the hydrogel group (P < 0.01). (4) The wound healing rate in the copper phosphate nanohydrogel group at 5 and 7 days was higher than that in the control group and the hydrogel group (P < 0.05); the collagen deposition rate was higher than that in the control group and the hydrogel group (P < 0.01); the number of neovascularizations was higher than that in the control group and the hydrogel group; and the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins was higher than that in the control group and the hydrogel group (P < 0.05). (5) The results exhibit that the copper phosphate nanohydrogel dressing can upregulate the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor and promote collagen deposition and angiogenesis, thereby accelerating skin wound healing in mice.
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    Preparation and cytocompatibility of sodium alginate-hydroxyapatite-graphene oxide hydrogels
    Li Xuanze, Fang Hanhong, Xu Zhe
    2026, 30 (32):  8420-8426.  doi: 10.12307/2026.420
    Abstract ( 12 )   PDF (2899KB) ( 6 )   Save
    BACKGROUND: Graphene oxide composite hydrogels exhibit various excellent properties, such as mechanical properties, biocompatibility, and controllable degradation, making them of great research and application value.
    OBJECTIVE:To analyze the physicochemical properties and cytocompatibility of sodium alginate-hydroxyapatite-graphene oxide hydrogels. 
    METHODS: Sodium alginate-hydroxyapatite, sodium alginate-hydroxyapatite-8 g/L graphene oxide, sodium alginate-hydroxyapatite-10 g/L graphene oxide, and sodium alginate-hydroxyapatite-12 g/L graphene oxide solutions were prepared. The viscosity of the four groups of solutions was measured. The four groups of solutions were cross-linked in CaCl2 solution to obtain hydrogels, which were denoted as SA-HA, SA-HA-8 g/L GO, SA-HA-10 g/L GO, and SA-HA-12 g/L GO, respectively. The compressive elastic modulus, compressive stress, in vitro degradation rate, equilibrium swelling ratio, and microstructure of the four groups of hydrogels were characterized. The four groups of hydrogels were co-cultured with rat bone marrow mesenchymal stem cells. Cell proliferation was detected by CCK-8 assay. Cell viability was observed by Live/Dead fluorescence staining. Cell adhesion was observed by scanning electron microscopy.
    RESULTS AND CONCLUSION: (1) The addition of graphene oxide significantly increased the viscosity of the hydrogel solution, with the SA-HA-10 g/L GO group showing the best viscosity, which met the requirements for hydrogel shaping. With the addition of graphene oxide and the increase in its concentration, the compressive elastic modulus and compressive stress of the hydrogels increased, the in vitro degradation rate decreased, and the porosity initially increased and then decreased, with the SA-HA-10 g/L GO group having the highest porosity. The addition of graphene oxide reduced the equilibrium swelling ratio of the hydrogels. Scanning electron microscopy showed that all four groups of hydrogels had porous structures, and the pore size decreased with the addition of graphene oxide and the increase in its concentration. (2) Scanning electron microscopy showed that the SA-HA group material had the least cell adhesion on its surface, while the SA-HA-10 g/L GO group material had the most cell adhesion. CCK-8 assay showed that after 3, 5, and 7 days of culture, the cell absorbance values of the SA-HA-8 g/L GO group, SA-HA-10 g/L GO group, and SA-HA-12 g/L GO group were higher than that of the SA-HA group (P < 0.05). Live/Dead fluorescence staining showed that the cell viability of the SA-HA-8 g/L GO group, SA-HA-10 g/L GO group, and SA-HA-12 g/L GO group was higher than that of the SA-HA group (P < 0.05), and the cell viability of the SA-HA-10 g/L GO group was higher than that of the SA-HA-8 g/L GO group and SA-HA-12 g/L GO group (P < 0.05). (3) The results exhibit that the SA-HA-10 g/L GO hydrogel has superior cytocompatibility, a suitable degradation rate, and sufficient mechanical properties.
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    Quercetin-loaded hydrogel materials for treatment of infected bone defects
    Liu Bangding, Tang Yongliang, Li Ni, Ren Bo
    2026, 30 (32):  8427-8435.  doi: 10.12307/2026.396
    Abstract ( 13 )   PDF (4057KB) ( 5 )   Save
    BACKGROUND: Traditional topical administration of antibiotics for infected bone defects is limited by the selective proliferation of drug-resistant strains, burst drug release, and a lack of osteoinductive activity. Simple bone repair materials are ineffective in controlling the infection process. Therefore, the development of intelligent drug delivery systems with multiple biological functions has become a research hotspot in this field. 
    OBJECTIVE: To construct a polyethylenimine/oxidized dextran dynamic cross-linked hydrogel-loaded quercetin composite system to achieve a temporally synergistic antibacterial and osteogenic effect and to investigate the efficacy of this composite system in treating infected bone defects.  
    METHODS: (1) Oxidized dextran was prepared by sodium periodate oxidation, and quercetin nanocrystals were prepared by antisolvent precipitation. Quercetin nanocrystals were then added to a polyethylenimine solution and a Schiff base reaction was used to prepare a quercetin-loaded polyethylenimine/oxidized dextran hydrogel. The in vitro drug release from this hydrogel was characterized. (2) In vitro experiments: Rabbit bone marrow mesenchymal stem cells were seeded onto the surfaces of polyethyleneimine/oxidized dextran hydrogels and quercetin-loaded polyethyleneimine/oxidized dextran hydrogels, respectively. Cells cultured alone served as controls, and the cytocompatibility of the materials was assessed using CCK-8 assay and live-dead cell staining. After osteogenic induction, the osteogenic capacity of the materials was evaluated using alkaline phosphatase staining, Alizarin Red staining, and osteogenic gene detection. Staphylococcus aureus (or Escherichia coli, methicillin-resistant Staphylococcus aureus) was co-cultured with polyethyleneimine/oxidized dextran hydrogels and quercetin-loaded polyethyleneimine/oxidized dextran hydrogels, respectively. The bacteria cultured alone were used as the control. The antibacterial properties of the materials were evaluated by measuring the absorbance of the bacterial suspension and applying the bacterial suspension to a culture dish, respectively. (3) Animal experiment: SD rats were drilled below the greater trochanter of the left femur and bone marrow was aspirated. A 5% sodium morrhuate + Staphylococcus aureus suspension was injected into the bone marrow cavity to establish an infected femoral defect model. Four weeks after modeling, rats were randomly divided into three intervention groups: a control group (n=9) underwent only thorough debridement; a hydrogel group (n=9) and a quercetin-loaded hydrogel group (n=9) underwent thorough debridement followed by injection of a polyethyleneimine/oxidized dextran hydrogel or a quercetin-loaded polyethyleneimine/oxidized dextran hydrogel, respectively. Eight weeks after surgery, specimens were harvested for micro-CT scanning and histomorphological observation.
    RESULTS AND CONCLUSION: (1) The polyethyleneimine/oxidized dextran hydrogel rapidly released the drug initially (within 3 days) and then released the drug slowly for up to 42 days. (2) CCK-8 assay and live-dead cell staining showed that the quercetin-loaded polyethyleneimine/oxidized dextran hydrogel promoted cell proliferation and exhibited good cytocompatibility compared with the polyethyleneimine/oxidized dextran hydrogel. Absorbance measurements of bacterial suspensions and culture dish coating experiments revealed that the polyethyleneimine/oxidized dextran hydrogel had no antibacterial properties, while the quercetin-loaded polyethyleneimine/oxidized dextran hydrogel significantly inhibited the growth and reproduction of Staphylococcus aureus, Escherichia coli, and methicillin-resistant Staphylococcus aureus. Alkaline phosphatase staining, Alizarin red staining, and osteogenic gene analysis revealed that the polyethyleneimine/oxidized dextran hydrogel had no osteogenic activity, while the quercetin-loaded polyethyleneimine/oxidized dextran hydrogel exhibited excellent osteogenic activity. (3) Micro-CT scans revealed that the quercetin-loaded hydrogel group produced significantly more new bone tissue than the control and hydrogel groups. Hematoxylin-eosin and Masson staining revealed that the quercetin-loaded hydrogel group exhibited superior bone defect repair quality compared with the control and hydrogel groups. Giemsa staining revealed that numerous bacteria were observed in the control and hydrogel groups, while the quercetin-loaded hydrogel group was virtually devoid of bacteria. (4) The results showed that the quercetin-loaded polyethyleneimine/oxidized dextran hydrogel exhibited excellent antibacterial and osteogenic properties, promoting the repair of infected bone defects. 
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    Antibacterial properties of photocrosslinkable hydrogel loaded with quercetin-silver nanoparticles for infected wounds
    Chen Shichao, Deng Yunyi, Zhao Renshengjie, Yu Ke, Li Guangwen
    2026, 30 (32):  8436-8442.  doi: 10.12307/2026.458
    Abstract ( 23 )   PDF (7968KB) ( 5 )   Save
    BACKGROUND: Numerous studies have confirmed that quercetin can inhibit the release of inflammatory factors and reduce local inflammatory responses in wounds, creating favorable conditions for wound healing. However, quercetin suffers from poor water solubility and low bioavailability, limiting its application in wound treatment.
    OBJECTIVE: To investigate the antibacterial properties of quercetin-silver nanoparticles (QuAgNPs)/methacrylated hyaluronic acid (HAMA) composite hydrogels. 
    METHODS: (1) QuAgNPs were synthesized by hydrothermal reduction. QuAgNPs were loaded into methacrylated hyaluronic acid hydrogel precursor solution at different concentrations (1, 5, 10, 20, 40, 60, and 80 μg/mL) to prepare composite hydrogels, denoted as 1, 5, 10, 20, 40, 60, and 80 μg/mL QuAgNPs/HAMA hydrogels. A pure HAMA hydrogel was also prepared. Staphylococcus aureus was co-cultured with 1, 5, 10, 20, 40, 60, and 80 μg/mL QuAgNPs/HAMA hydrogels, and antibacterial properties were detected by the inhibition zone assay. The in vitro drug release performance of 60 and 80 μg/mL QuAgNPs/HAMA hydrogels was also tested. Based on the inhibition zone assay results, a suitable QuAgNPs/HAMA hydrogel was selected for subsequent experiments. (2) The microstructure of HAMA hydrogel and 60 μg/mL QuAgNPs/HAMA hydrogel was observed under a scanning electron microscope. Staphylococcus aureus (or Escherichia coli) was co-cultured with QuAgNPs, HAMA hydrogel, and 60 μg/mL QuAgNPs/HAMA hydrogel, with bacteria cultured alone as a blank control. The antibacterial rate was detected by the plate coating antibacterial experiment. Human umbilical vein endothelial cells were co-cultured with QuAgNPs, HAMA hydrogel extract, and 60 μg/mL QuAgNPs/HAMA hydrogel extract, respectively, with cells cultured alone as a blank control. Cell viability was detected by live/dead cell staining. 
    RESULTS AND CONCLUSION: (1) The inhibition zone experiment showed that the antibacterial performance of 60 and 80 μg/mL QuAgNPs/HAMA hydrogels was stronger than that of 1, 5, 10, 20, and 40 μg/mL QuAgNPs/HAMA hydrogels, and there was no difference in antibacterial performance between 60 and 80 μg/mL QuAgNPs/HAMA hydrogels. Both 60 and 80 μg/mL QuAgNPs/HAMA hydrogels exhibited good in vitro drug release performance. Therefore, 60 μg/mL QuAgNPs/HAMA hydrogel was selected for subsequent experiments. (2) Scanning electron microscopy showed that the HAMA hydrogel had a loose and porous structure, and approximately spherical QuAgNPs particles were scattered on the surface of the HAMA hydrogel in the 60 μg/mL QuAgNPs/HAMA hydrogel. The plate coating antibacterial experiment showed that QuAgNPs and 60 μg/mL QuAgNPs/HAMA hydrogel had significant inhibitory effects on both Staphylococcus aureus and Escherichia coli. Live/dead cell staining showed that QuAgNPs, HAMA hydrogel, and 60 μg/mL QuAgNPs/HAMA hydrogel did not affect cell viability and all had good cytocompatibility. (3) The results indicate that the QuAgNPs/HAMA composite hydrogel has good antibacterial properties. 
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    Characterization and biological performance of manganese-doped hydroxyapatite/polydopamine composite materials
    Yu Qiming, Di Jingyi, Zhang Hao, Chen Jilong, Xiao Hui, Hu Tuqiang
    2026, 30 (32):  8443-8453.  doi: 10.12307/2025.876
    Abstract ( 10 )   PDF (9597KB) ( 18 )   Save
    BACKGROUND: Hydroxyapatite is widely used in bone tissue engineering due to its excellent osteoconductivity. However, its limited osteoinductivity restricts its clinical application and therapeutic efficacy.
    OBJECTIVE: To prepare novel manganese-doped hydroxyapatite/polydopamine (Mn-HA/PDA) composite bone graft materials and characterize their physicochemical and biological properties.
    METHODS: (1) Using Ca(NO₃)₂·4H₂O as the calcium source, (NH4)2HPO4 as the phosphorus source, and manganese nitrate solution as the manganese source, manganese-doped hydroxyapatite was prepared by hydrothermal homogeneous coprecipitation with manganese/(calcium+manganese) molar ratios of 5%, 10%, and 15%, respectively. The corresponding materials were denoted as 5Mn-HA, 10Mn-HA, and 15Mn-HA. Hydroxyapatite and the three manganese-doped hydroxyapatite materials were immersed in dopamine hydrochloride-Tris buffer solution to prepare manganese-doped hydroxyapatite/polydopamine composite materials, denoted as HA/PDA, 5Mn-HA/PDA, 10Mn-HA/PDA, and 15Mn-HA/PDA, respectively. The morphology, manganese ion release, degradation rate, and cell compatibility of the materials were characterized. The manganese-doped material with better cell compatibility was selected for subsequent experiments. (2) Hydroxyapatite, HA/PDA, 5Mn-HA, and 5Mn-HA/PDA were co-cultured with rat bone marrow mesenchymal stem cells. After osteogenic induction, alkaline phosphatase activity detection and Alizarin Red S staining were performed, and Runx2 and osteocalcin mRNA expression levels were detected by q-PCR. (3) A 5 mm diameter full-thickness circular bone defect was created on both sides of the skull of 24 SD rats. Hydroxyapatite, HA/PDA, 5Mn-HA, and 5Mn-HA/PDA were implanted into the right bone defect (6 rats per material), while the left bone defect was untreated (blank control). Samples were collected at 4 and 8 weeks post-surgery for Micro-CT scanning, hematoxylin-eosin staining, and Masson staining.
    RESULTS AND CONCLUSION: (1) The manganese-doped hydroxyapatite/polydopamine composite material exhibited a microsphere morphology with a particle size distribution ranging from 9.86 to 13 μm. With increasing manganese doping concentration, the release of manganese ions from the material increased, and the manganese ion release rate of the manganese-doped hydroxyapatite/polydopamine composite material was lower than that of the corresponding manganese-doped hydroxyapatite material. Compared with manganese-doped hydroxyapatite, the manganese-doped hydroxyapatite/polydopamine composite exhibited a faster degradation rate. Based on the results of live/dead cell staining and CCK-8 assay of rat bone marrow mesenchymal stem cells, 5Mn-HA showed no significant cytotoxicity; therefore, 5Mn-HA and 5Mn-HA/PDA were selected for subsequent experiments. (2) Based on the results of alkaline phosphatase activity assay, Alizarin Red S staining, and q-PCR, 5Mn-HA/PDA exhibited stronger osteogenic differentiation ability than the other three materials. (3) Micro-CT scanning showed that the blank control group had the slowest bone repair rate and the least amount of new bone formation, while the 5Mn-HA/PDA group had the fastest bone repair rate and the most new bone formation. Hematoxylin-eosin and Masson staining further confirmed the Micro-CT scanning results. (4) The results indicate that the manganese-doped hydroxyapatite/polydopamine composite material possesses excellent physicochemical and biological properties.
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    In vitro drug release of polymyxin B sulfate-loaded bone cement
    Mao Jiaojiao, Qian Chenyue, Bi Feiyu, Bao Jianan
    2026, 30 (32):  8454-8459.  doi: 10.12307/2026.418
    Abstract ( 4 )   PDF (1628KB) ( 5 )   Save
    BACKGROUND: For diabetic foot infections, traditional vancomycin-loaded bone cement has a limited antibacterial spectrum, and there is an urgent need for novel drug carriers.
    OBJECTIVE: To explore the in vitro elution characteristics of polymyxin B sulfate-loaded bone cement. 
    METHODS: Polymyxin B sulfate powder was uniformly mixed with polymethyl methacrylate bone cement and poured into molds to prepare bone cement microspheres with diameters of 5 and 7 mm. The two types of bone cement microspheres of different diameters were immersed in 1 mL of PBS, and elution samples were collected at specific time points. The concentration of polymyxin B sulfate in the eluent was determined by mass spectrometry, and the drug release pattern was analyzed. 
    RESULTS AND CONCLUSION: (1) The drug release peaks for both types of bone cement microspheres occurred between 0 and 0.5 h, after which the release rate gradually decreased. Inter-group comparison showed that the drug release rate and cumulative release rate of the 5 mm diameter microspheres were higher than those of the 7 mm diameter microspheres. The cumulative drug release rates at 14 days for the 5 mm and 7 mm diameter microspheres were 5.08% and 3.37%, respectively. The drug release from both types of bone cement microspheres of different diameters reached 90% of the total release within 7 days, approaching the release endpoint. The in vitro drug release curves of both types of microspheres conformed to the Ritger-Peppas model (R2=0.998 56, 0.990 90), mainly driven by Fickian diffusion. (2) Polymyxin B sulfate-loaded bone cement exhibits certain sustained-release characteristics, with drug release mainly concentrated in the first 7 days, and low release in the later stages. Therefore, 5-7 days after implantation of polymyxin B bone cement is the optimal time for secondary debridement. Continued placement carries a higher risk of inducing bacterial resistance. The drug release rate is related to the size of the bone cement. In clinical applications, 5 mm diameter microspheres should be considered first to balance the needs for rapid drug release and long-lasting antibacterial effect.

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    Regulatory effects of optimized extraction processes for chlorella-derived peptides on key pathological links in rheumatoid arthritis
    Zhang Yiwei, Fang Ya, Sun Xin, Yang Han, Lin Haiyang, Chen Zhouhao, Zheng Yue, Fu Jingke, Wang Jinwu
    2026, 30 (32):  8460-8470.  doi: 10.12307/2026.495
    Abstract ( 20 )   PDF (3266KB) ( 10 )   Save
    BACKGROUND: Recent studies have shown that Chlorella possesses potential value in treating rheumatoid arthritis. The pathological progression of rheumatoid arthritis is closely associated with an imbalance in oxidative stress, abnormal macrophage polarization, aggressive activation of fibroblast-like synoviocytes, and disturbances in the vascular endothelial system. However, the optimization of extraction processes for peptides derived from Chlorella and their regulatory effects and mechanisms on key pathological links in rheumatoid arthritis require systematic validation.
    OBJECTIVE: To optimize the extraction process of antioxidant peptides from Chlorella, clarify their antioxidant activity and biosafety, and investigate their regulatory effects on the pathological phenotypes of rheumatoid arthritis-related cells (RAW 264.7 mouse monocyte-macrophage leukemia cells, fibroblast-like synoviocytes, and human umbilical vein endothelial cells), thereby providing experimental evidence for the therapeutic potential of Chlorella peptides in rheumatoid arthritis.
    METHODS: (1) Peptide extracts from Chlorella were prepared using bromelain enzymatic hydrolysis combined with the phosphomolybdic acid precipitation method. Using peptide yield as the indicator, extraction parameters including solid-to-liquid ratio, hydrolysis time, and reaction system pH were optimized through single-factor experiments. (2) Peptide content was determined by the BCA method. Antioxidant capacity was detected by the ABTS assay. The biosafety of the peptides on RAW 264.7, fibroblast-like synoviocytes, and human umbilical vein endothelial cells was evaluated using the CCK-8 assay. (3) A lipopolysaccharide-induced RAW 264.7 inflammation model was established. The effects of the peptides on intracellular reactive oxygen species levels and M1/M2 polarization phenotypes were detected via DCFH-DA staining, flow cytometry, and real-time quantitative reverse transcription polymerase chain reaction. (4) A tumor necrosis factor-α-induced fibroblast-like synoviocytes activation model was established. The effects of the peptides on fibroblast-like synoviocytes migration, proliferation, invasion capabilities, and the expression of related genes were assessed using scratch wound assay, EdU proliferation assay, Transwell invasion assay, and real-time quantitative reverse transcription polymerase chain reaction. (5) A vascular endothelial growth factor-A-induced abnormal activation model of human umbilical vein endothelial cells was established. The effects of the peptides on human umbilical vein endothelial cell migration, tube formation ability, and the expression of hypoxia-inducible factor 1-alpha, and vascular endothelial growth factor A genes were evaluated via scratch wound assay, Transwell assay, tube formation assay, and real-time quantitative reverse transcription polymerase chain reaction.  
    RESULTS AND CONCLUSION: (1) The optimal extraction conditions for Chlorella peptides were a solid-to-liquid ratio of 2:1 (g:100 mL), an enzymatic hydrolysis time of 60 minutes, and a reaction system pH of 6.5, under which the highest peptide yield was achieved. (2) Chlorella peptides exhibited concentration-dependent antioxidant activity and showed no significant cytotoxicity against RAW 264.7, fibroblast-like synoviocytes, and human umbilical vein endothelial cells within the concentration range of 1–10 μg/mL, indicating good biocompatibility. (3) The Chlorella peptides dose-dependently inhibited lipopolysaccharide-induced reactive oxygen species generation in RAW 264.7 cells, downregulated the expression of M1-type pro-inflammatory genes such as interleukin-1β and tumor necrosis factor-α, and upregulated the expression of M2-type anti-inflammatory genes such as interleukin-10 and arginase-1, thereby promoting macrophage polarization from the M1 phenotype towards the M2 phenotype. (4) The Chlorella peptides significantly inhibited tumor necrosis factor-α-induced migration, proliferation, and invasion capabilities of fibroblast-like synoviocytes and downregulated the expression of related genes including interleukin-6, matrix metalloproteinase-13, tumor necrosis factor receptor superfamily member 11A, and C-X-C motif chemokine ligand 12. (5) The Chlorella peptides effectively inhibited vascular endothelial growth factor A-induced migration and tube formation ability of human umbilical vein endothelial cells and reduced the expression levels of hypoxia-inducible factor-1α and vascular endothelial growth factor A genes. It is concluded that Chlorella peptides exert multi-target regulatory effects on rheumatoid arthritis pathological links through antioxidative stress, modulation of macrophage polarization, inhibition of the aggressive phenotype of fibroblast-like synoviocytes, and amelioration of vascular endothelial disturbances, demonstrating potential therapeutic value for rheumatoid arthritis.
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    Spinal injury risk assessment of a double-layer cushion for ejection seats based on ABAQUS
    Yan Jin, Xu Mengzhen, Bao Jiayi
    2026, 30 (32):  8471-8478.  doi: 10.12307/2026.459
    Abstract ( 22 )   PDF (2108KB) ( 5 )   Save
    BACKGROUND: The enormous impact acceleration experienced by the human body during ejection is a major risk factor for spinal injury. Therefore, optimizing the cushioning and energy absorption design of ejection seat cushions is crucial for ensuring the safety of pilots.
    OBJECTIVE: To construct a human-seat cushion coupled finite element model based on ABAQUS to quantitatively evaluate the impact of a double-layer cushion, which combines the advantages of high and slow rebound, on lumbar spine biomechanical response and spinal injury risk under ejection conditions, and to quantify its safety margin.
    METHODS: CT imaging data of the entire spine and legs from one male pilot volunteer were selected. Three-dimensional anatomical reconstruction, geometric repair, and finite element meshing were completed to construct a highly biologically faithful digital human model encompassing the entire spine, pelvis, both femurs, and skin soft tissues. A geometric model of the dual-layer seat cushion was also established. Subsequently, a human-chair system coupled model was assembled in ABAQUS. Dynamic simulations were conducted by applying an ejection acceleration time history. Stress responses in the L4–L5 and L5–S1 intervertebral discs were compared between the high-resilience and dual-layer cushion designs. Injury probability was predicted using the Spinal Injury Risk Dynamic Response Index.
    RESULTS AND CONCLUSION: The simulation results demonstrated good consistency with actual measurement data, effectively validating the model's accuracy. Performance comparison analysis indicated that, compared with conventional seat cushions, the dual-layer cushion reduced peak stresses in the L4–L5 and L5–S1 intervertebral discs during ejection impact. This solution reduces the dynamic response index by 1.8%, lowering the predicted probability of spinal injury by 10.6%. While meeting relevant limits, it provides a higher safety margin and can effectively reduce the risk of spinal injury to the human body under ejection impact loads.

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    Potential and application prospects of combined treatment of acute myocardial infarction with hydrogel cardiac patches and traditional Chinese medicine
    Ding Hao, Gao Yuan, Li Bin, Yu Rui, Wang Jianru, Sun Yudie, Wang Xuanyang, Zhang Wenping, Zhu Mingjun
    2026, 30 (32):  8479-8486.  doi: 10.12307/2026.297
    Abstract ( 19 )   PDF (13664KB) ( 28 )   Save
    BACKGROUND: Hydrogel cardiac patches, with their excellent biocompatibility and tunable mechanical properties, demonstrate significant potential in treating acute myocardial infarction, particularly when combined with stem cell technology. Hydrogels modified with active ingredients from traditional Chinese medicine can promote the proliferation, differentiation, migration, and homing of stem cells. This synergistic effect provides a new approach for stem cell transplantation based on hydrogel cardiac patches.
    OBJECTIVE: To focus on exploring the application scenarios of novel biomaterials—hydrogel cardiac patches combined with traditional Chinese medicine—in treating myocardial infarction and to discuss their development prospects. 
    METHODS: Literature on the application of traditional Chinese medicine combined with hydrogel cardiac patches in acute myocardial infarction treatment was retrieved from PubMed and China National Knowledge Infrastructure (CNKI) databases. The search period spanned January 2010 to January 2025. Chinese and English search terms included "hydrogel, cardiac patch, myocardial infarction, Chinese medicine, stem cell, drug delivery system." Based on inclusion and exclusion criteria, 99 articles were ultimately included in this review.
    RESULTS AND CONCLUSION: Hydrogel cardiac patches, with their excellent biocompatibility, adjustable mechanical properties, and drug loading capacity, provide ideal mechanical support and microenvironment for myocardial repair. Hydrogel cardiac patches, as hydrophilic polymer biomaterials, possess a three-dimensional network structure that highly mimics the physical properties of the natural extracellular matrix of heart cells. This provides a microenvironment for the propagation and viability of loaded biological cells, aiding in cell migration, adhesion, diffusion, differentiation, and the formation of intercellular connections. Loading stem cells onto hydrogels modified with traditional Chinese medicine allows for thorough induction and regulation of stem cells, enabling more effective cell regeneration therapy in the infarcted area and achieving better repair effects. Therefore, the combined application of traditional Chinese medicine and hydrogel cardiac patches has enormous development potential and prospects. Currently, the combined application of traditional Chinese medicine and hydrogel patches focuses on the following aspects: achieving precise sustained-release therapy of traditional Chinese medicine active ingredients through loading onto hydrogel cardiac patches; inducing pluripotent stem cells for cell regeneration therapy via traditional Chinese medicine-modified hydrogel patches; and combining traditional Chinese medicine with conductive hydrogels to repair cardiac electrophysiological function. Future research requires a deeper understanding of the properties of hydrogels prepared using different materials and methods, as well as the therapeutic effects and application mechanisms of traditional Chinese medicine monomers and compound extracts, to achieve more combined applications of traditional Chinese medicine and hydrogel cardiac patches. 
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    Application strategies of DNA hydrogels for tissue repair
    Fei Xiaoyuan, Xu Jiao, Shi Hui
    2026, 30 (32):  8487-8495.  doi: 10.12307/2026.298
    Abstract ( 16 )   PDF (3955KB) ( 3 )   Save
    BACKGROUND: DNA hydrogels possess thermal resilience, thixotropy, enzyme responsiveness, and degradability. Further functionalization with chemical modifications, peptides, aptamers, and other elements can endow hydrogels with unique responsiveness, demonstrating their immense potential as smart materials.
    OBJECTIVE: To summarize fabrication strategies, functional properties, and applications of DNA hydrogels.
    METHODS: PubMed and CNKI databases were searched using "DNA hydrogel, tissue engineering, tissue regeneration" as English and Chinese search terms. Based on inclusion criteria, 76 relevant articles were selected for in-depth analysis.
    RESULTS AND CONCLUSION: Current research has established diverse preparation methods for DNA hydrogels, including: nanomodule assembly, rolling circle amplification, or hybridization chain reaction for pure DNA hydrogels; hybrid DNA hydrogels formed by grafting DNA onto polymers with crosslinking; interpenetrating networks combining polymers and DNA nanostructures; and physically crosslinked hydrogels through non-covalent interactions. Modularly self-assembled variants exhibit shear-thinning and self-healing properties, enabling injectable delivery for irregular wound repair and bone regeneration with precise filling capabilities. DNA hydrogels effectively load, protect, and deliver bioactive components while mimicking the extracellular matrix to facilitate 3D cell culture or serve as cell-laden carriers to the injury site, providing a delivery and application platform for stem cell therapies in bone repair and nerve regeneration. DNA hydrogels can also achieve integrated diagnosis and treatment, intelligently responding to the needs of different diseases. However, the clinical translation of DNA hydrogels still faces many challenges: immunoreactivity remains controversial; current laboratory synthesis of DNA hydrogels is small-scale and costly; and to further improve the application effects of DNA hydrogels, it is necessary to explore the integration of bioactive molecules into the hydrogels to enhance therapeutic efficacy.
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    Hydrogel-based drug delivery systems for rheumatoid arthritis treatment
    Li Minghui, Qie Haoyu, Pan Min, Bi Ruijie, Lyu Xiaomeng, Zhang Haoya, Han Yifei
    2026, 30 (32):  8496-8501.  doi: 10.12307/2026.873
    Abstract ( 11 )   PDF (8100KB) ( 18 )   Save
    BACKGROUND: In recent years, hydrogels have become an important research direction in the treatment of rheumatoid arthritis due to their excellent biocompatibility, controllable drug release performance, and advantages in multiple drug delivery routes.
    OBJECTIVE: To systematically review the application of hydrogel-based materials as drug delivery carriers in the treatment of rheumatoid arthritis, and explore the impact of different administration routes on the therapeutic effect. 
    METHODS: Using “hydrogel, rheumatoid arthritis, smart hydrogel system, injectable hydrogel, intra-articular injection, transdermal drug delivery” as Chinese and English search terms, we searched PubMed, Web of Science, CNKI, WanFang Data, and VIP. Based on the inclusion criteria, 62 articles were finally included for review.
    RESULTS AND CONCLUSION: Hydrogels, leveraging their three-dimensional network structures and tunable physicochemical properties, not only allows drugs to accurately reach the lesion area but also significantly prolongs the retention time of drugs in the joint cavity, making them an ideal carrier in the field of drug delivery. The drug release mechanisms of hydrogels mainly include diffusion, chemical regulation, and swelling-mediated release; in addition, stimulus-responsive hydrogels can dynamically regulate drug release behavior based on environmental conditions (such as pH, temperature, enzyme concentration, etc.). In the treatment of rheumatoid arthritis, common administration routes for hydrogel drug delivery systems include parenteral administration, oral administration, transdermal administration, and intra-articular injection, which significantly reduce systemic adverse reactions, improve drug absorption efficiency, and enhance patient compliance. Although hydrogel systems as drug delivery carriers have shown significant application potential in the treatment of rheumatoid arthritis, long-term safety, biodegradability, and large-scale production still need to be addressed to promote the clinical translation of hydrogel drug delivery carriers.

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    Application of self-healing hydrogels for sports injury prevention and rehabilitation#br#
    Meng Yihao, Zhang Shuai
    2026, 30 (32):  8502-8511.  doi: 10.12307/2026.461
    Abstract ( 12 )   PDF (1465KB) ( 3 )   Save
    BACKGROUND: A novel smart material, namely self-healing hydrogel, has caught much attention in sports medicine and rehabilitation engineering. This is on account of its high water content, favorable biocompatibility, tailorable mechanical traits, and the intrinsic ability to self-heal after sustaining. 
    OBJECTIVE: To systematically survey the progress of self-healing hydrogels in the prevention, treatment, and rehabilitation of sports injuries.
    METHODS: A search was conducted on authoritative domestic and international databases including CNKI, X-mol, and PubMed. Research literature involving self-healing hydrogels and sports medicine was selected. English and Chinese search terms included "self-healing hydrogel, sports injury repair, activity monitoring, smart rehabilitation, wearable sensors." Based on the inclusion criteria, 136 articles were finally included in this review.
    RESULTS AND CONCLUSION: Self-healing hydrogels are really good at repairing ligaments, tendons, cartilage and bone tissue. They provide essential mechanical support and help cells to stick together, grow and develop. By releasing drugs or growth factors at a controlled rate, they can reduce inflammation, provide pain relief and speed up recovery. In the fields of motion monitoring and rehabilitation, these self-healing materials are used as core layers in flexible sensors. These sensors monitor movement, posture and joint stress in real time. They use virtual reality, augmented reality, and telemedicine to make rehabilitation training more intelligent and precise. Self-healing hydrogels are progressively evolving toward integrated platforms that combine monitoring, therapy, and rehabilitation. Although substantial progress has been achieved in recent years, challenges remain in terms of mechanical durability, rapid healing efficiency, large-scale manufacturing, and clinical translation. Future research should focus on the design and optimization of high-strength, multi-stimuli-responsive hydrogels, while integrating sports biomechanics with artificial intelligence to establish data-driven and personalized rehabilitation models. Moreover, advancing interdisciplinary collaboration and developing standardized evaluation systems will be essential to provide more scientific and standardized strategies for the prevention, intervention, and rehabilitation of sports injuries.

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    Applications and advances of hydrogels in bone tissue engineering repair related to sports injuries
    Jin Yuan, Zhou Jiabing
    2026, 30 (32):  8512-8520.  doi: 10.12307/2026.286
    Abstract ( 14 )   PDF (1334KB) ( 5 )   Save
    BACKGROUND: Hydrogel, as a highly biomimetic and modifiable biomaterial, shows a broad application prospect in the field of bone tissue engineering.
    OBJECTIVE: To review the current research status and development trend of hydrogel in bone tissue engineering.
    METHODS: The PubMed and CNKI databases were searched for articles on the application of hydrogels in bone tissue engineering. Chinese and English search terms were “hydrogel, bone tissue engineering, nanomaterials, bone regeneration mechanism, bone defect repair.” Based on the inclusion and exclusion criteria, 113 articles were included for review.
    RESULTS AND CONCLUSION: To improve how hydrogels work for bone tissue engineering, researchers have used different strategies to add new functions. These include changing their physical and chemical properties, adding biological components, and strengthening them with other materials. The goal is to make hydrogels more compatible with the body, stronger, able to break down at a controlled rate, and better at delivering drugs. Functionalized hydrogels help bones regenerate through several ways: by influencing how cells interact, regulating growth factors and signaling pathways, controlling mechanical signals and the surrounding environment, and acting as drug and nano-delivery systems. Future research on hydrogels will concentrate on building systems that combine multiple functions. For instance, by adding features that respond to temperature, pH, enzymes, or magnetic fields, the release of biological factors or drugs can be controlled in specific locations and at specific times, improving their ability to dynamically affect bone regeneration. Developing polymeric materials that are biodegradable, mechanically adjustable, and adaptable to the microenvironment will improve their stability and integration within complex physiological conditions. Precise 3D printing technology will be used to create scaffolds with controlled structures, distinct functional zones, and designs tailored to match the unique structural characteristics of bone defect of each patient.

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    Hydrogel scaffolds in tissue engineering for urethral repair and reconstruction
    Qiu Jiajing, Huang Liqu
    2026, 30 (32):  8521-8528.  doi: 10.12307/2026.453
    Abstract ( 11 )   PDF (1265KB) ( 7 )   Save
    BACKGROUND: In recent years, hydrogel scaffolds, as important carriers in the field of tissue engineering, have made significant progress in their application in urethral repair and reconstruction.
    OBJECTIVE: To systematically review the design strategies of urethral tissue engineering scaffolds, the functional modification of hydrogel scaffolds, and their application progress in urethral repair, and to explore the future development directions and clinical transformation challenges of hydrogel scaffolds.
    METHODS: The CNKI and PubMed databases were searched using Chinese and English keywords "hydrogel, tissue engineering scaffold, urethral tissue engineering, urethral repair, urethral reconstruction." Based on the inclusion criteria, 69 articles were finally selected for inductive analysis.
    RESULTS AND CONCLUSION: In urethral tissue engineering, urethral scaffolds should not only possess basic characteristics such as biocompatibility but also exhibit unique properties that adapt to the structure of the urethra and the urethral environment. Hydrogel scaffolds can be divided into natural hydrogel scaffolds (commonly including protein hydrogel scaffolds, polysaccharide hydrogel scaffolds, DNA hydrogel scaffolds, and extracellular matrix hydrogel scaffolds) and synthetic polymer hydrogel scaffolds (commonly including polyvinyl alcohol, polyacrylic acid, and acrylate-based hydrogel scaffolds). Cross-linking methods mainly include physical cross-linking and chemical cross-linking, and preparation methods mainly include in-situ gelation, freeze-drying, electrospinning, and 3D bioprinting. To avoid the shortcomings of single materials, composite materials are currently widely used to prepare hydrogel scaffolds for urethral tissue engineering, such as composite hydrogel scaffolds suitable for the urethral microenvironment, composite hydrogel scaffolds utilizing decellularized extracellular matrix, multilayer composite hydrogel scaffolds loaded with stem cells, and hydrogel scaffolds based on non-stem cells. With the development of tissue engineering and regenerative medicine, future hydrogel scaffolds should be designed towards intelligent, engineered, and cell-free directions, while also considering current clinical translation obstacles and proposing comprehensive solutions.
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    Properties of machinable resin-ceramic composites and their application in onlay restorations
    Huang Rongjie, Bao Xuemei
    2026, 30 (32):  8529-8535.  doi: 10.12307/2026.878
    Abstract ( 17 )   PDF (1465KB) ( 3 )   Save
    BACKGROUND: Resin-ceramic composites have gradually become an important choice for onlay restoration materials due to their advantages such as good aesthetics, elastic modulus close to that of dental tissues, excellent repair performance, and high efficiency in manufacturing processes.
    OBJECTIVE: To review the performance of computer-aided design and computer-aided manufacturing (CAD/CAM) milled resin-ceramic composite materials and their current application in minimally invasive onlay restorations.
    METHODS: Using "machinable resin ceramic material, nano resin ceramic, resin-infiltrated ceramic, onlay" as Chinese keywords and "CAD/CAM resin ceramic, resin nano ceramic, polymer-infiltrated ceramic network, onlay" as English keywords, a systematic search was conducted in the CNKI and PubMed databases. The search covered relevant literature published from January 2020 to August 2025, with a small number of earlier publications also included. The titles and abstracts of the retrieved literature were initially screened, and the full texts of the selected literature were thoroughly reviewed. Studies with low relevance to the content of this review, incomplete data, or duplicate research were excluded, resulting in the final selection of 76 articles for this review.
    RESULTS AND CONCLUSION: Machinable resin-ceramic composites are a type of chairside restorative material composed of resin and inorganic ceramics, mainly classified into two categories: nano resin-ceramics and resin-infiltrated ceramics. Existing research data and clinical applications show that their mechanical properties are close to those of traditional glass ceramics, their elastic modulus is compatible with dentin, and they possess excellent fatigue resistance and wear resistance. After targeted surface treatment, their bonding strength with dentin can be significantly improved, and they maintain stable performance in the complex oral environment. When applied to onlay restoration, machinable resin-ceramic composites can achieve high repair success rates, retention rates, and patient satisfaction by strictly selecting indications, avoiding high-risk factors, and following the principle of minimally invasive preparation. At present, various complications such as fracture and debonding still exist in their actual clinical application, so more relevant research is needed to further improve material performance and optimize clinical application effect. 


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    Material selection and manufacture method of non-porous adherent cell microcarriers
    Sun Jingshan, Deng Jingqian, Qi Liya, Zhao Xiaohuan, Hou Dandan
    2026, 30 (32):  8536-8543.  doi: 10.12307/2026.470
    Abstract ( 12 )   PDF (1955KB) ( 3 )   Save
    BACKGROUND: The key consumable item in stirred-tank bioreactors is non-porous microcarriers, which are suitable for adherent cell culture and play a significant role in the fabrication of viruses, recombinant proteins, and stem cells.
    OBJECTIVE: To summarize the material selection and manufacturing methods of non-porous microcarriers based on the favorable conditions for cell-microcarrier adhesion. 
    METHODS: A computerized search of CNKI, PubMed, and Web of Science databases was performed with the search terms “cell cultivation, adherent cells, microcarrier, fibronectin, bioreactor, microsphere preparation” in Chinese and “cell adhesion, microcarrier, bioreactor, dextran, cell-matrix interaction, suspension culture” in English. The search time limit was from 1967 to 2025. After screening according to the inclusion and exclusion criteria, 52 articles were finally included for summary analysis.
    RESULTS AND CONCLUSION: Non-porous microcarriers are suitable for adherent cell culture at a density of 109-1010 cells/L. Due to the requirements for cell adhesion, non-porous microcarriers need to provide appropriate surface positive charge or integrin binding sites. Non-porous microcarriers made of dextran, polystyrene, and collagen have been commercialized and can widely support large-scale culture of various cell types. While reports exist of large-scale cell culture using non-porous microcarriers made of chitosan and cellulose, these new materials have not yet been commercialized. Dextran and polystyrene microcarriers have been commercialized for a long time, with mature preparation methods including cross-linking and polymerization, respectively. Collagen and cellulose microcarriers are mostly prepared using cross-linking methods, while chitosan microcarriers can be prepared using both cross-linking and phase inversion methods.

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    Mechanism of action of extracellular vesicles loaded with biomaterials in repairing spinal cord injury
    Zheng Ying, Li Mengyao, Zheng Fanfan, He Zhao, Zhang Ning, Zou Jialun, Li Youlei, Gao Feng
    2026, 30 (32):  8544-8554.  doi: 10.12307/2026.428
    Abstract ( 12 )   PDF (13973KB) ( 16 )   Save
    BACKGROUND: Combining exosomes with biomaterials such as hydrogels and biological scaffolds enables targeted delivery, providing effective support for damaged tissue and significantly enhancing the therapeutic efficiency of exosomes, thus positively impacting spinal cord injury repair.
    OBJECTIVE: To review the action mechanisms and research progress of exosomes combined with biomaterials in spinal cord injury.
    METHODS: Databases including CNKI, PubMed, and Web of Science were searched using the Chinese and English search terms “spinal cord injury, exosomes, hydrogel, biological scaffold, neuroinflammation, oxidative stress, axonal regeneration, angiogenesis.” Based on the inclusion criteria, 106 articles were finally included in this review.
    RESULTS AND CONCLUSION: Current research focuses on the repair of secondary injury after spinal cord injury, and how to better alleviate the damage caused by secondary injury is a key research question. Exosomes combined with biomaterials treat spinal cord injury mainly through regulating neuroinflammation, promoting axonal regeneration, and alleviating oxidative stress. This approach avoids immune rejection, addresses the problem of low exosome bioavailability, and provides effective tissue support to the injured site, effectively alleviating secondary symptoms after spinal cord injury. Most studies on exosome-loaded biomaterials for treating spinal cord injury are limited to cell and animal experiments, lacking clinical trial data. More mechanistic studies, safety evaluations, and relevant clinical trials are needed in the future.

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    4D bioprinting for regenerative medicine: a new strategy for intelligent material regulation and tissue regeneration
    Liao Meixi, Wang Zhenxing, Lu Lili
    2026, 30 (32):  8555-8562.  doi: 10.12307/2026.452
    Abstract ( 17 )   PDF (1995KB) ( 1 )   Save
    BACKGROUND: 4D printing enables dynamic control of structure and function, allowing constructs to more closely mimic complex physiological environments and driving the development of tissue engineering and regenerative medicine towards intelligence and personalization.
    OBJECTIVE: To review the role and application advances of 4D printing in tissue engineering and regenerative medicine.
    METHODS: Relevant literature published between 1994 and 2025 was retrieved from CNKI, WanFang, PubMed, and Web of Science. Chinese and English terms were “4D printing, regenerative medicine, tissue engineering, wound healing, biological ink, intelligent materials.” A total of 115 articles were systematically reviewed and analyzed. 
    RESULTS AND CONCLUSION: 4D bioprinting represents a key advance in tissue engineering and regenerative medicine, integrating diverse fabrication methods and biomaterials to create structures that dynamically respond to environmental cues. 4D bioprinting enhances the biomimicry of natural tissues, enables customized responsiveness, and improves integration with biological systems. 4D bioprinting facilitates the development of tissues and organs, as well as intelligent implants and advanced drug delivery systems, thereby supporting tissue repair. By adapting seamlessly to physiological complexity, 4D bioprinting contributes to personalized medicine and significantly improves therapeutic outcomes under dynamic conditions.

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    Application of novel materials in tissue repair of diabetic foot wounds
    Xia Jinyan, Su Meifang, Yang Wenyu, Hu Qilan, Gong Li
    2026, 30 (32):  8563-8568.  doi: 10.12307/2026.886
    Abstract ( 10 )   PDF (2130KB) ( 2 )   Save
    BACKGROUND: In recent years, the convergence of materials science and biomedical engineering has opened new avenues for diabetic foot wound treatment. Novel biomaterials such as multifunctional hydrogels, tissue engineering scaffolds, and nanoparticle systems have become a research hotspot.
    OBJECTIVE: To analyze, through bibliometric analysis, the design principles and biological functions of novel materials used in diabetic foot wound treatment, their potential in addressing the complex pathological challenges of diabetic foot, and to forecast future directions and challenges in this field.
    METHODS: We searched the Web of Science database for literature on novel materials for diabetic foot wound treatment from its inception until June 2025. CiteSpace software was used for bibliometric and visual analysis.
    RESULTS AND CONCLUSION: From 1979 to 2025, the publication output in the field of novel materials for treating diabetic foot ulcers showed an overall fluctuating upward trend, with an explosive growth period observed between 2022 and 2025. The United States had the highest number of publications (602), followed by China (284) and India (166). Among institutions, Sichuan University had the highest publication volume, followed by Tehran University of Medical Sciences. Ranked by the total influence of publications, Sichuan University ranked first, followed by Nankai University. Among hospitals, West China Hospital had the highest publication count, followed by Beth Israel Deaconess Medical Center and Thomas Jefferson University Hospital. Ranked by the influence of publications, West China Hospital remained first, followed by Shanghai Ninth People’s Hospital and Thomas Jefferson University Hospital. Among enterprises/groups, Success Bio-Tech Co. Ltd., Engineering Software Research and Development Inc., and Foot and Ankle Associates of Central Illinois LLC were tied for first place in publication count (each with 2 publications). Ranked by influence, Organogenesis Inc. had the highest influence, followed by Food Industry Research Co. Among journals, Wounds had the highest number of publications (96), followed by Foot Ankle Int (40) and Cureus (38). Among authors, Bus, Sicco A. had the most publications (12), followed by Lázaro-Martínez, José Luis (8). Ranked by publication influence, the GBD 2021 collaborative research groups (including the US Burden of Disease and Forecasting Collaborators, Diabetes Collaborators, Obesity Collaborators, Adult and Adolescent BMI Collaborators, Causes of Death Collaborators, etc.) had the highest influence.

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    Application and development of polyetheretherketone material in skull defect repair
    Zhang Zhanyue, Zhao Lijun, Zhang Chunyang, Zhang Zhongqi, Fu Kang, Zhang Zhihong
    2026, 30 (32):  8569-8576.  doi: 10.12307/2026.874
    Abstract ( 12 )   PDF (25543KB) ( 16 )   Save
    BACKGROUND: Polyetheretherketone, a high-performance synthetic material prized for its low density, high strength, excellent toughness, favorable processing characteristics, and biocompatibility, is still becoming a primary choice for repairing skull defects. However, systematic bibliometric studies specifically analyzing its application in cranial repair are scarce. 
    OBJECTIVE: To summarize the overall research trend, development trajectory, research focus, and hotspots of polyetheretherketone materials in the field of skull defect repair internationally using bibliometric methods.
    METHODS: The Web of Science Core Collection database system was searched for the literature on the application of polyetheretherketone materials in skull defect repair from 1995 to 2024. Subsequently, quantitative statistical and visual analyses were performed using bibliometric techniques, focusing on temporal trends in publication volume, contributions by country/region, collaborative networks of core research institutions, highly cited papers, prolific journals, and keyword co-occurrence.
    RESULTS AND CONCLUSION: In this work, we analyzed 105 articles on polyetheretherketone for skull defect repair covering 2009 to 2024. We found that the field was divided into three phases. From 2009 to 2014, the focus was on traditional materials; from 2015 to 2019, on clinical research of polyetheretherketone; and from 2020 to 2024, on 3D printing and finite element analysis, with the 2020-2024 phase accounting for 42% of the total. Meanwhile, the combinations of “3D printing and finite element analysis” and “polyetheretherketone and titanium alloy” are high-frequency technology pairs. China (21 articles), USA (17 articles), and Germany (12 articles) are the main research countries. Polyetheretherketone has been clinically used in more than 200,000 cases worldwide, with an infection rate of 3.7%, which is lower than the infection rate of 9.2% reported for polymethylmethacrylate. Research on polyetheretherketone has shifted from “passive repair” to “active bioactivity promotion.” Europe and USA are leading the clinical translation of 3D printing (82% device availability versus 39% in China), but there is a lag time of about 2 years between published literature and clinical application for 3D-printed polyetheretherketone. Conductive polyetheretherketone is predicted to accelerate translation from 2026 to 2027. These findings suggest that polyetheretherketone has achieved the transformation from “passive repair” to “active biological activity promotion,” with 3D printing, surface modification, and intelligent integration as the core directions. The global development of polyetheretherketone is uneven, with high demand but less research in underdeveloped regions (12%). China focuses on clinical research domestically (68%) but shows insufficient basic innovation (15%). It is necessary to promote low-cost 3D printing technology, establish transformation hubs, support interdisciplinary teams, and build a 10-year multi-center follow-up system.  

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