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    18 September 2026, Volume 30 Issue 26 Previous Issue    Next Issue
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    Three-dimensional printed isoniazid liposome photothermal composite scaffolds and their performance evaluation
    Yang Guang, Yin Zhitao, Xu Yan
    2026, 30 (26):  6701-6709.  doi: 10.12307/2026.844
    Abstract ( 27 )   PDF (12693KB) ( 16 )   Save
    BACKGROUND: Drug-loaded bone scaffolds for tuberculosis treatment suffer from problems such as drug burst release in the early stages of treatment and insufficient drug release in the later stages, which leads to low drug concentration at the lesion, therefore, it is imperative to build a drug controlled-release system on the tissue-engineered bone scaffolds.
    OBJECTIVE: To prepare photothermal composite scaffolds with different isoniazid liposome doping ratios and characterize their mechanical and biological properties.
    METHODS: Isoniazid liposomes were prepared using the thin-film hydration method. The microstructure, encapsulation efficiency, drug loading capacity, particle size, and Zeta potential of liposomes were characterized. 15 mg of isoniazid was selected as the total drug amount for a single drug-loaded scaffold. Isoniazid drug powder, isoniazid liposome powder at 2%, 5%, and 8% of the total drug amount, respectively, were mixed uniformly with the scaffold base material (hydroxyapatite and β-tricalcium phosphate in a mass ratio of 6:4) and 3% of the photothermal agent polypyrrole nanoparticles (by mass fraction of the scaffold base material) to prepare extrusion printing powders. 13% polyvinyl alcohol gel was added to the extrusion printing powder in a 1:1 mass ratio. Pure isoniazid scaffolds and three kinds of isoniazid liposome photothermal scaffolds were fabricated using extrusion-based 3D bioprinting. The microstructure, porosity, mechanical properties, and drug release performance of the photothermal scaffolds were characterized. Mouse embryonic osteoblasts (MC3T3 cells) were cultured with extracts from the four kinds of scaffolds. The cytotoxicity of the scaffolds was detected using the MTT assay.
    RESULTS AND CONCLUSION: (1) Under transmission electron microscopy, isoniazid liposomes appeared as spherical vesicles with a relatively regular shape. The encapsulation efficiency of isoniazid liposomes was (28.67±0.62)%, the drug loading capacity was (3.54±0.19)%, the average particle size was (363.63±10.42) nm, and the average Zeta potential was (-4.68±0.72) mV. (2) Scanning electron microscopy showed that compared with the pure isoniazid scaffold, the isoniazid liposome photothermal scaffold had more pores internally. With the increase of isoniazid liposome content, the porosity of the photothermal scaffold showed an increasing trend, while the compressive strength and elastic modulus showed a decreasing trend, but still met the minimum compressive strength required for tissue implantation experiments in animals. The incorporation of isoniazid liposomes effectively solved the problem of drug burst release in the early stage of drug release from the scaffold, and the cumulative drug release rate in the early stage was inversely proportional to the amount of isoniazid liposomes incorporated. After irradiation with an 808 nm near-infrared laser, the cumulative drug release rate of the isoniazid liposome photothermal scaffold increased compared with that without near-infrared laser irradiation. With the increase of isoniazid liposome content, the photothermal controlled release performance of the scaffold became more significant in the later stage of drug release. MTT assay showed that the relative proliferation rate of MC3T3 cells cultured with the extracts of the four kinds of scaffolds for 24, 72, and 120 hours was all greater than 70%, indicating no significant cytotoxicity. The results show that the isoniazid liposome photothermal scaffold has good mechanical properties, drug-controlled release performance, and cytocompatibility.

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    In vitro osteogenic and anti-inflammatory properties of icariin sustained-release microsphere three-dimensional scaffolds
    Zhao Zhanghong, Jin Dongsheng, Ruan Shiqiang, Huang Wenliang, Wan Yu, Tian Renyuan, Deng Jiang
    2026, 30 (26):  6710-6718.  doi: 10.12307/2026.804
    Abstract ( 55 )   PDF (3228KB) ( 26 )   Save
    BACKGROUND: Icariin has the dual activity of promoting bone formation and inhibiting bone resorption, but its clinical application is plagued by low bioavailability, difficulty in controlling dosage, and a high risk of adverse reactions.
    OBJECTIVE: To prepare a three-dimensional scaffold containing icariin sustained-release microspheres and characterize their osteogenic activity in vitro.
    METHODS: A silk fibroin/chitosan/nanohydroxyapatite three-dimensional scaffold (SF/CS/nHA scaffold), icariin sustained-release microspheres, and a silk fibroin/chitosan/nanohydroxyapatite three-dimensional scaffold loaded with icariin sustained-release microspheres (SF/CS/nHA-ICA scaffold) were prepared. The drug loading efficiency, encapsulation efficiency, and in vitro drug release of the icariin sustained-release microspheres were characterized. The pore size, porosity, water swelling rate, and hot water solubility of the two scaffolds were also characterized. Rabbit bone marrow mesenchymal stem cells (or human rheumatoid arthritis fibroblast-like synoviocytes) were seeded onto SF/CS/nHA scaffolds and SF/CS/nHA-ICA scaffolds, respectively. Cells cultured alone served as controls. Adhesion of the two cell types was observed under a scanning electron microscope. Cell proliferation and activity were assessed using CCK-8 assay, live/dead staining, and F-actin staining. The mRNA and protein expressions of Runx-2, osteocalcin, and type I collagen in bone marrow mesenchymal stem cells were determined using RT-qPCR and western blot assay.
    RESULTS AND CONCLUSION: (1) The drug loading rate and encapsulation efficiency of icariin sustained-release microspheres were (29.38±0.04)% and (52.01±0.09)%, respectively, and icariin could be released sustainably in vitro for more than 90 days. (2) Scanning electron microscopy revealed that the interior of the two scaffolds showed a honeycomb-like porous structure with interconnected pores. There were no significant differences in pore size, porosity, water absorption expansion rate, and total hot water solubility between the two scaffolds (P > 0.05). (3) Scanning electron microscopy revealed that both cell types were tightly attached to the scaffold surface and pores, with extended pseudopodia on the surface of the SF/CS/nHA-ICA scaffold. CCK-8 assay, live/dead staining, and F-actin staining showed that the SF/CS/nHA-ICA scaffold enhanced the proliferation and viability of rabbit bone marrow mesenchymal stem cells and inhibited the proliferation and viability of human rheumatoid arthritis fibroblast-like synoviocytes compared with the control group and the SF/CS/nHA scaffold. (4) RT-qPCR and western blot assay revealed that the mRNA and protein expressions of Runx-2, osteocalcin, and type I collagen were increased in the SF/CS/nHA-ICA group compared with the control group and the SF/CS/nHA group (P < 0.05). (5) The results indicate that the icariin sustained-release microsphere three-dimensional scaffold has good cytocompatibility, in vitro osteogenesis, and anti-inflammatory effects.

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    Osteogenic and antibacterial properties of polyether ether ketone modified by multifunctional composite coating
    Zhang Huifang, Li Hankai, Huang Haozhe, Liu Min, Wang Pin, Huang Haixia, Sun Libo, Lan Yuyan
    2026, 30 (26):  6719-6728.  doi: 10.12307/2026.361
    Abstract ( 41 )   PDF (4814KB) ( 129 )   Save
    BACKGROUND: Polyether ether ketone (PEEK) has insufficient inherent biological activity. As a bone implant material, there are risks of poor osseointegration and implant-associated infections. The development of PEEK surface modification strategies with both osteogenic and antibacterial functions has important clinical significance for improving the implantable performance of PEEK.
    OBJECTIVE: To analyze the biocompatibility, osteogenic and antibacterial effects of polydopamine-modified strontium-doped hydroxyapatite-silver composite coating PEEK. 
    METHODS: (1) A polydopamine-hydroxyapatite composite coating was prepared on the surface of PEEK, recorded as PEEK@PDA-HA. According to the ratio of Sr2+/(Sr2++Ca2+) of 0%, 5%, 10%, and 20%, respectively, a polydopamine-strontium-doped hydroxyapatite-silver composite coating was prepared on the surface of PEEK, recorded as PEEK@PDA-HA-Ag, PEEK@PDA-5Sr/HA-Ag, PEEK@PDA-10Sr/HA-Ag, and PEEK@PDA-20Sr/HA-Ag, respectively. MC3T3-E1 cells were co-cultured with PEEK, PEEK@PDA-HA-Ag, PEEK@PDA-5Sr/HA-Ag, PEEK@PDA-10Sr/HA-Ag, and PEEK@PDA-20Sr/HA-Ag. The best materials were selected for subsequent experiments through cell proliferation, live-dead staining, and adhesion test results. The surface morphology and water contact angle of PEEK@PDA-10Sr/HA-Ag were characterized. (2) MC3T3-E1 cells were inoculated on the surfaces of PEEK, PEEK@PDA-HA, PEEK@PDA-HA-Ag, and PEEK@PDA-10Sr/HA-Ag. Alkaline phosphatase staining, alizarin red staining, and osteocalcin immunofluorescence staining were performed after osteogenic induction to detect the osteogenic differentiation performance of the materials. (3) Escherichia coli (or Staphylococcus aureus) was co-cultured with PEEK, PEEK@PDA-HA, PEEK@PDA-HA-Ag, and PEEK@PDA-10Sr/HA-Ag. The antibacterial properties of the materials were detected by agar plate counting method and bacterial live and dead staining. 
    RESULTS AND CONCLUSION: (1) The results of cell proliferation, live and dead staining, and adhesion detection showed that PEEK@PDA-10Sr/HA-Ag had the best effect on promoting MC3T3-E1 cell proliferation. At the same time, the MC3T3-E1 cells adhered to the surface of the material had good morphology and extended more filopodia, which could be used for subsequent experiments. Scanning electron microscopy showed that the surface of PEEK@PDA-10Sr/HA-Ag was rough and uneven, with a large number of spherical nanoparticles attached. Compared with PEEK, the water contact angle of the surface of PEEK@PDA-10Sr/HA-Ag was reduced, and the hydrophilicity was enhanced. (2) Alkaline phosphatase staining, alizarin red staining, and osteocalcin immunofluorescence staining showed that PEEK@PDA-10Sr/HA-Ag had the strongest osteogenic effect. (3) Bacterial plate counts and live-dead staining showed that PEEK@PDA-10Sr/HA-Ag could effectively inhibit the growth of Escherichia coli and Staphylococcus aureus compared with the other three groups of materials. (4) The results showed that PEEK loaded with polydopamine modified strontium-doped hydroxyapatite-silver composite coating had good biocompatibility, osteogenic and antibacterial effects.

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    Preparation and characterization of beta-tricalcium phosphate/polyvinyl alcohol and hydroxyapatite/polyvinyl alcohol bone substitute materials
    Hu Zhizhao, Liu Zhaoyong, Guo Jing, Jin Shengnan, Zhou Qiqi, Hu Yang
    2026, 30 (26):  6729-6735.  doi: 10.12307/2026.837
    Abstract ( 27 )   PDF (7910KB) ( 16 )   Save
    BACKGROUND: Currently, many oral periodontal bone substitute materials suffer from drawbacks such as poor biomechanical properties and degradation characteristics. Using composite periodontal bone substitute materials can compensate for the shortcomings of single materials and better facilitate the construction of "periodontal bone tissue engineering constructs."
    OBJECTIVE: To prepare β-tricalcium phosphate/polyvinyl alcohol and hydroxyapatite/polyvinyl alcohol composite materials using freeze-drying method and characterize their properties.
    METHODS: A 15% polyvinyl alcohol hydrogel was prepared. Different amounts of β-tricalcium phosphate were added to the polyvinyl alcohol hydrogel. After freeze-drying, 10%, 20%, and 30% β-tricalcium phosphate/polyvinyl alcohol composite materials were obtained. Similarly, different amounts of hydroxyapatite were added to the polyvinyl alcohol hydrogel, and after freeze-drying, 10%, 20%, and 30% hydroxyapatite/polyvinyl alcohol composite materials were obtained. The properties of each group of composite materials were characterized using scanning electron microscopy, X-ray energy dispersive spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and Raman spectroscopy.
    RESULTS AND CONCLUSION: (1) Scanning electron microscopy and X-ray energy dispersive spectroscopy analysis showed that β-tricalcium phosphate and hydroxyapatite particles successfully formed stable composite materials with the polyvinyl alcohol hydrogel. With increasing concentrations of β-tricalcium phosphate or hydroxyapatite, the aggregation of β-tricalcium phosphate/polyvinyl alcohol and hydroxyapatite/polyvinyl alcohol composite material particles increased, and the porosity decreased. The main elements in each group of composite materials included Ca, P, C, and O. (2) X-ray photoelectron spectroscopy, X-ray diffraction, and Raman spectroscopy results showed that no new bending vibration peaks, stretching vibration peaks, or characteristic peaks appeared in the β-tricalcium phosphate/polyvinyl alcohol and hydroxyapatite/polyvinyl alcohol composite materials. It is indicated that the β-tricalcium phosphate/polyvinyl alcohol and hydroxyapatite/polyvinyl alcohol composite materials prepared by freeze-drying method exhibited stable properties.

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    3D printed neobavaisoflavone-coated scaffolds promote bone regeneration by regulating osteoblast/osteoclast activities
    Pi Zhilong, Li Jiayuan, Tan Zhichao, Lu Xiaomei, Zhang Zhiqiang, Ye Xiangling
    2026, 30 (26):  6736-6743.  doi: 10.12307/2026.409
    Abstract ( 31 )   PDF (5035KB) ( 59 )   Save
    BACKGROUND: Neobavaisoflavone could promote bone formation and may be a potential small molecule drug for bone regeneration. The use of 3D printed bone tissue engineering scaffolds as drug delivery carriers for neobavaisoflavone is expected to enhance the potential application of bone regeneration.
    OBJECTIVE: To explore the effects of polylactic acid/polydopamine/neobavaisoflavone bone scaffold on osteoclast and osteoblast activity. 
    METHODS: (1) Fused deposition modeling technology was used to manufacture a 3D printed polylactic acid scaffold. These polylactic acid scaffolds were immersed in a dopamine solution containing or without neobavaisoflavone to produce polylactic acid/polydopamine/neobavaisoflavone scaffolds and polylactic acid/polydopamine scaffolds, respectively. The surface morphology, surface hardness, and compressive strength of the three groups of scaffolds were characterized, and the drug release properties of the polylactic acid/polydopamine/neobavaisoflavone scaffolds were investigated. (2) Mouse embryonic osteoblasts MC3T3-E1 were co-cultured with the three groups of scaffolds. The cytocompatibility of the scaffolds was assessed using CCK-8 assay and live-dead cell staining. The effects of the scaffolds on osteoblast migration were evaluated using Transwell assays. The effects of the scaffolds on osteoblast differentiation were assessed using alkaline phosphatase quantification and Alizarin red staining. RAW264.7 cells were co-cultured with the three groups of scaffolds. After osteoclast induction, the effects of the scaffolds on osteoclast differentiation were assessed by tartrate-resistant acid phosphatase staining. 
    RESULTS AND CONCLUSION: (1) Scanning electron microscopy revealed that all three groups of scaffolds exhibited a three-dimensional structure with regularly interconnected porous structures, with an average pore size of 400 µm. The surface hardness and compressive strength of the polylactic acid/polydopamine scaffold and the polylactic acid/polydopamine/neobavaisoflavone scaffold were significantly higher than those of the polylactic acid scaffold (P < 0.05). The polylactic acid/polydopamine/neobavaisoflavone scaffold exhibited excellent drug release, with sustained drug release for over 14 days in vitro. (2) CCK-8 assay and live-dead cell staining demonstrated that all three groups of scaffolds exhibited good cytocompatibility. The polylactic acid/polydopamine scaffold and the polylactic acid/polydopamine/neobavaisoflavone scaffold promoted the proliferation of MC3T3-E1 cells. Transwell assay showed that compared with the polylactic acid scaffold, the polylactic acid/polydopamine scaffold and the polylactic acid/polydopamine/neobavaisoflavone scaffold promoted MC3T3-E1 cell migration. Alkaline phosphatase quantification assay and Alizarin red staining revealed that the polylactic acid/polydopamine scaffold and the polylactic acid/polydopamine/neobavaisoflavone scaffold promoted osteogenic differentiation of MC3T3-E1 cells compared with the other two scaffolds. Tartrate-resistant acid phosphate staining revealed that the polylactic acid/polydopamine/neobavaisoflavone scaffold inhibited osteoclast differentiation of RAW264.7 cells. (3) These results demonstrate that the polylactic acid/polydopamine/neobavaisoflavone scaffold has good biosafety and can promote bone regeneration by regulating osteoclast and osteoblast activity. 
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    Comparison of different 3D-printed allogeneic bone and artificial polymer composite porous scaffold materials for repairing cranial bone defects in rats
    Liu Weiwei, Gou Yuanbin, Cui Xiaoxue, Li Xin, Liu Dawei, Shi Mengrou, Chen Bin, Li Zhifeng
    2026, 30 (26):  6744-6751.  doi: 10.12307/2026.845
    Abstract ( 40 )   PDF (3875KB) ( 12 )   Save
    BACKGROUND: Allogeneic bone repair materials have good effect on bone defect repair, but they have drawbacks such as immune rejection, high cost, and low rigidity.
    OBJECTIVE: To evaluate the bone repair ability, tissue response and degradation performance of three kinds of 3D-printed allogeneic bone and artificial polymer composite porous scaffold materials.
    METHODS: Three kinds of bone repair materials were prepared: (1) Sample A: A bone repair material was prepared by mixing polylactic acid-glycolic acid copolymer with allogeneic bone powder at a mass ratio of 1:4, using low-temperature deposition 3D printing. (2) Sample B: A bone repair material was prepared by mixing polycaprolactone with allogeneic bone powder at a mass ratio of 1:4, using low-temperature deposition 3D printing. (3) Sample C: A bone repair material was prepared by mixing polycaprolactone with allogeneic bone powder at a mass ratio of 3:7, using high-temperature melt 3D printing. A 5 mm diameter circular bone defect was created on each side of the sagittal suture in 35 SD rats. Ten defects received no intervention (blank control group), 15 defects were implanted with allogeneic bone material (positive control group), 15 defects were implanted with sample A (sample A group), 15 defects were implanted with sample B (sample B group), and 15 defects were implanted with sample C (sample C group). Samples were collected at 2, 4, 8, 12, and 26 weeks post-surgery. Hematoxylin-eosin staining was used to observe material degradation, tissue response at the implantation site, and new bone formation. Masson staining was used to observe collagen fiber formation. Immunohistochemical staining was used to observe the expression of RUNT-related transcription factor 2 and type I collagen.
    RESULTS AND CONCLUSION: (1) Hematoxylin-eosin staining: During the experimental period, all implanted materials showed varying degrees of degradation. Samples A and B degraded faster, followed by the positive control, while sample C degraded more slowly. With time, the inflammatory response in all implanted material groups showed a decreasing trend, but fibrous tissue hyperplasia and neovascularization remained relatively significant. At 26 weeks post-surgery, the inflammatory response in sample A group was significantly reduced, followed by sample B group and the positive control group, while the reduction trend in sample C group was not obvious. A small amount of new bone formation was observed in sample B group at 8 weeks post-surgery, and new bone formation was observed in sample A group and the positive control group at 12 weeks post-surgery. A large amount of new bone formation was observed in these three groups at 26 weeks post-surgery. No significant new bone formation was observed in sample C group throughout the study. (2) Masson staining: At 2 weeks post-surgery, a small amount of irregularly arranged collagen deposition was observed in all implanted material groups. At 26 weeks post-surgery, a large amount of regularly arranged collagen deposition was observed in all implanted material groups. (3) Immunohistochemical staining: With time, RUNT-related transcription factor 2 and type I collagen expression increased in all implanted material groups. The expression of RUNT-related transcription factor 2 and type I collagen in the positive control group, sample A group, and sample B group at 12 and 26 weeks post-surgery was higher than that in sample C group. (4) The results showed that samples 3D printed with polylactic acid-glycolic acid copolymer or polycaprolactone and allogeneic bone powder at low temperature degraded faster, showed less inflammatory response, and exhibited more significant osteogenic factor expression and new bone formation compared with samples printed with high-content polycaprolactone and allogeneic bone powder at high temperature.

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    Multi-objective optimization of coronary artery stent design in ensemble surrogate model
    Zhang Ke, Wang Peiyao, Wang Bohan, Zhu Yuting, Wang Chuan
    2026, 30 (26):  6752-6759.  doi: 10.12307/2026.743
    Abstract ( 30 )   PDF (2189KB) ( 38 )   Save
    BACKGROUND: Percutaneous coronary intervention stent implantation is primarily used to treat coronary artery stenosis. However, current multi-objective stent optimization methods are limited by sample size constraints, resulting in insufficient prediction accuracy when balancing key performance indicators such as support and compliance, hindering the effectiveness of stent optimization design.
    OBJECTIVE: To establish an innovative optimization framework for coronary stents based on a ensemble surrogate model.
    METHODS: A three-dimensional parametric model of the vascular stent was constructed, and a mechanical response database was established through finite element simulation. A dynamic weight fusion strategy was adopted to integrate the global optimization characteristics of the Kriging model and the local nonlinear representation advantages of the radial basis function model. A ensemble surrogate model was constructed based on 20 groups of initial samples, and the non-dominated sorting genetic algorithm-II was used to optimize the parameter space.
    RESULTS AND CONCLUSION: Experimental results demonstrated that the ensemble surrogate model exhibited significant advantages in the finite sample setting. The coefficient of determination for the inverse prediction of the radial stiffness of the stent reached 0.974 2, a 4.4% improvement compared to the single model, validating the efficient modeling capability of the ensemble surrogate model in the finite sample setting. The prediction accuracy of the stent's bending stiffness also improved by 4.4% compared to the single radial basis function surrogate model. After optimization, the stent performance achieved dual-objective collaborative optimization. The inverse radial stiffness of the stent in the ensemble surrogate model group was reduced by 13.92% and 9.57% compared to the Kriging model group and the single radial basis function model surrogate group, respectively. The stent's bending stiffness was improved by 0.38% and 2.56% compared to the Kriging model group and the single radial basis function model surrogate group, respectively. The proposed ensemble surrogate model overcomes the performance limitations of traditional single models and provides a low-cost, high-precision solution for the "rigidity-flexibility" collaborative optimization of coronary stents. 

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    Ginsenoside Rg3-loaded liposome hydrogel promotes chondrogenic differentiation of stem cells
    Zhao Qinglan, Zhou Xinting, Wang Huajun, Zhong Jiaxuan, Zheng Liheng, Tan Wencheng, Yang Xinchun, Huang Shusen, Wu Tingting, Zheng Xiaofei, Hong Jinsong
    2026, 30 (26):  6760-6767.  doi: 10.12307/2026.766
    Abstract ( 42 )   PDF (4188KB) ( 21 )   Save
    BACKGROUND: Ginsenoside Rg3 has potential for cartilage protection and repair, but its application suffers from drawbacks such as poor water solubility, short half-life, and low bioavailability. To improve drug pharmacokinetic properties, embedding drug-loaded liposomes into methylated gelatin, polysaccharide, or silk fibroin-based hydrogels has become a hot topic in cartilage tissue engineering research.
    OBJECTIVE: To fabricate liposome-methacryloylated silk fibroin hydrogels loaded with ginsenoside Rg3 and further analyze the effects of these hydrogels on the chondrogenic differentiation of mouse bone marrow mesenchymal stem cells.
    METHODS: (1) Ginsenoside Rg3 liposomes were prepared by a thin film dispersion method. Dil-labeled liposomes were co-cultured with mouse bone marrow mesenchymal stem cells, and cellular uptake of the liposomes was assessed by phalloidin staining. Methacryloylated silk fibroin (SilMA) was prepared. Ginsenoside Rg3 liposomes were mixed with SilMA and photocrosslinked to form a composite hydrogel (SilMA@Lipo-Rg3). The micromorphology, mechanical properties, rheological properties, swelling properties, and drug release performance of the hydrogel were evaluated. (2) Mouse bone marrow mesenchymal stem cells were cultured with different concentrations of SilMA hydrogel extract or SilMA@Lipo-Rg3 hydrogel extract. The cytocompatibility of the materials was evaluated by CCK-8 assay and live-dead cell staining. Mouse bone marrow mesenchymal stem cells were cultured with 1/8 concentration of SilMA hydrogel extract or SilMA@Lipo-Rg3 hydrogel extract, respectively. After chondrogenic induction, the expression of type II collagen, SOX9, and aggrecan mRNA was measured by qPCR. The expression of intracellular proteoglycans and glycosaminoglycans was detected by Alcian blue and safranin O staining.
    RESULTS AND CONCLUSION: (1) Phalloidin staining revealed that Dil-labeled liposomes were successfully taken up by mouse bone marrow mesenchymal stem cells. Scanning electron microscopy revealed that the SilMA@Lipo-Rg3 hydrogel exhibited a loose and porous lattice structure. Compression tests and rheological tests revealed that the compressive stiffness of the SilMA@Lipo-Rg3 hydrogel was slightly lower than that of the SilMA hydrogel; there was no significant difference in the swelling properties of the two hydrogels. The SilMA@Lipo-Rg3 hydrogel exhibited excellent sustained-release properties, releasing ginsenoside Rg3 for more than 14 days. (2) CCK-8 assay and live-dead cell staining revealed that the SilMA and SilMA@Lipo-Rg3 hydrogels exhibited good cytocompatibility. qPCR analysis showed that the mRNA expression of type II collagen, SOX9, and aggrecan in the SilMA@Lipo-Rg3 group was higher than that in the SilMA group (P < 0.05). Alcian blue and safranin O staining revealed that the expression of proteoglycans and glycosaminoglycans in the SilMA@Lipo-Rg3 group was higher than that in the SilMA group. These results indicate that the SilMA@Lipo-Rg3 hydrogel promotes the chondrogenic differentiation of mouse bone marrow mesenchymal stem cells.
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    Fabrication and characterization of hydrogels with both antibacterial and osteogenic functions
    Zhou Yunqi, Liu Xu, Xiao Dongqin, Li Xingping, Shi Feng, Zhang Bo, Pu Chao, Luo Xuwei, Zhang Chengdong
    2026, 30 (26):  6768-6778.  doi: 10.12307/2026.374
    Abstract ( 21 )   PDF (13626KB) ( 17 )   Save
    BACKGROUND: Hydrogel materials have garnered significant attention in the field of tissue repair due to their excellent biocompatibility and biodegradability. However, the clinical application of hydrogel materials is hindered by their limited functionality, particularly the absence of antimicrobial and osteogenic properties. 
    OBJECTIVE: To design hydrogels with both antibacterial and osteogenic properties for bone tissue repair.
    METHODS: (1) Hydroxyapatite co-doped with copper and zinc ions was synthesized by chemical precipitation. Double-ion-doped hydroxyapatite, epigallocatechin gallate, and double-ion-doped hydroxyapatite + epigallocatechin gallate were added to a photoinitiator, respectively. Methacrylated gelatin was added to either the photoinitiator alone or the aforementioned photoinitiator, respectively. The hydrogels were cured under 405 nm ultraviolet light for 20 seconds to obtain methacrylated gelatin hydrogels (denoted as G), double-ion-doped hydroxyapatite/methacrylated gelatin hydrogels (denoted as G-Cu/Zn HA), epigallocatechin gallate-modified methacrylated gelatin hydrogels (denoted as G-E), and epigallocatechin gallate-modified double-ion-doped hydroxyapatite/methacrylated gelatin hydrogels (denoted as G-E-Cu/Zn HA). The micromorphology, compressive mechanical properties, swelling properties, degradation properties, and release kinetics of metal ions and epigallocatechin gallate of the four hydrogels were characterized. (2) Staphylococcus aureus (or Escherichia coli) cultures were co-cultured with each of the four hydrogel groups. The antibacterial properties of each hydrogel group were evaluated by agar plate coating, live/dead staining, and scanning electron microscopy. (3) The four hydrogel groups were co-cultured with MC3T3-E1 cells. The cytocompatibility of each hydrogel group was evaluated by live/dead staining and CCK-8 assay. After co-culture with MC3T3-E1 cells, osteogenic activity of each hydrogel group was evaluated by alkaline phosphatase staining, Alizarin Red S staining, and expression of osteogenesis-related genes after osteogenic induction.
    RESULTS AND CONCLUSION: (1) Scanning electron microscopy revealed that the cross-sections of all four hydrogel groups exhibited a loose and porous internal structure. The surfaces of the G and G-E hydrogels were relatively smooth, while the pore walls of the G-Cu/Zn HA and G-E-Cu/Zn HA hydrogels showed increased surface roughness. The compressive stresses of the G, G-E, G-Cu/Zn HA, and G-E-Cu/Zn HA hydrogels were 10.48, 12.91, 23.64, and 41.03 kPa, respectively. Compared with the G hydrogel, the G-E, G-Cu/Zn HA, and G-E-Cu/Zn HA hydrogels exhibited shortened overall swelling times and decreased swelling equilibrium rates. The degradation cycle of the G-E-Cu/Zn HA hydrogel was prolonged compared with the other three hydrogel groups. The G-Cu/Zn HA and G-E-Cu/Zn HA hydrogels continuously released Cu2+, Zn2+, and Ca2+ over 30 days, with the total amount of Cu2+ and Zn2+ released from the G-Cu/Zn HA hydrogel exceeding that from the G-E-Cu/Zn HA hydrogel. Compared with G-E hydrogel, G-E-Cu/Zn HA hydrogel significantly inhibited the burst release of epigallocatechin gallate. (2) Agar plate spread assay, live/dead staining, and scanning electron microscopy revealed that compared with G hydrogel, the other three hydrogel groups all exhibited antibacterial activity, with G-E-Cu/Zn HA hydrogel exhibiting the strongest inhibitory activity. (3) Live/dead staining and CCK-8 assay revealed that all four hydrogel groups exhibited good cytocompatibility. Alkaline phosphatase staining, Alizarin Red S staining, and osteogenesis-related gene expression assay revealed that G hydrogel exhibited the weakest osteogenic activity, while G-E-Cu/Zn HA hydrogel exhibited the strongest osteogenic activity. (4) These results demonstrate that the epigallocatechin gallate-modified dual-ion-doped hydroxyapatite/methacrylated gelatin composite hydrogel exhibits excellent antibacterial and osteogenic properties.
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    Curcumin-loaded chitosan/beta-glycerophosphate sodium thermoresponsive hydrogel promotes tendon healing in rats
    Zhang Yibo, Li Jian, Wang Peng, Jiang Qing
    2026, 30 (26):  6779-6798.  doi: 10.12307/2026.803
    Abstract ( 46 )   PDF (5810KB) ( 17 )   Save
    BACKGROUND: Tendon injury repair is often compromised by inflammatory cascades and disordered collagen metabolism, leading to scar formation and mechanical deterioration. Curcumin exhibits anti-inflammatory, antioxidant, and pro-repair potential, but its rapid metabolism and low bioavailability limit clinical application.
    OBJECTIVE: To construct a thermosensitive injectable curcumin-loaded chitosan/sodium β-glycerophosphate hydrogel and evaluate its efficacy in tendon repair.
    METHODS: (1) Rat tendon stem cells were cultured with different concentrations of curcumin for 24 hours. Cell viability was assessed using the CCK-8 assay, and the 20 µmol/L concentration was selected for subsequent experiments. Rat tendon stem cells were cultured with 0 (control) and 20 µmol/L curcumin, and cell migration was assessed using a wound healing assay. Rat tendon stem cells were cultured in three groups: a control group received no treatment; a model group received tert-butyl hydroperoxide to induce oxidative stress, and a curcumin group received tert-butyl hydroperoxide plus 20 µmol/L curcumin. qRT-PCR was used to analyze the mRNA expression of matrix metalloproteinases 3, 13, type I collagen α1 chain, and type III collagen α1 chain. Western blot assay was used to analyze the protein expression of matrix metalloproteinases 3, 13, Bcl-2, Bax, type I collagen α1 chain, and type III collagen α1 chain. (2) Thermosensitive injectable chitosan/sodium β-glycerophosphate hydrogels and curcumin-loaded chitosan/sodium β-glycerophosphate hydrogels (final concentration 20 µmol/L) were prepared and characterized for their micromorphology and drug release. Rat tendon stem cells were co-cultured with either hydrogel, with cells cultured alone serving as the control group. Live/dead staining and cytoskeleton staining were used to assess the cytocompatibility of the hydrogels. (3) Sixty SD rats were randomly divided into a sham operation group (n=12, Achilles tendon rupture model established after incision and suture), a model group (n=12, Achilles tendon rupture model established), a simple hydrogel group (n=12, Achilles tendon stump injected with chitosan/sodium β-glycerophosphate thermosensitive injectable hydrogel, followed by a second injection 4 days later), a drug group (n=12, Achilles tendon stump injected with 20 μmol/L curcumin solution, followed by a second injection 4 days later), and a drug-loaded hydrogel group (n=12, Achilles tendon stump injected with curcumin-loaded chitosan/sodium β-glycerophosphate thermosensitive injectable hydrogel, followed by a second injection 4 days later). Eight weeks after surgery, tissue samples were collected for peritendinous tissue adhesion assessment, hematoxylin-eosin staining, Masson staining, immunohistochemical staining for cyclooxygenase-2 and type I collagen α1 chain, and biomechanical analysis.
    RESULTS AND CONCLUSION: (1) Wound healing assay showed that curcumin promoted the migration of rat tendon stem cells. Compared with the model group, the curcumin group showed decreased mRNA and protein expressions of matrix metalloproteinase-3, matrix metalloproteinase-13, type III collagen α1 chain, and Bax protein (P < 0.05), while increased mRNA and protein expressions of type I collagen α1 chain and Bcl-2 protein (P < 0.05). This suggests that curcumin regulates tendon stem cell function through multiple targets. (2) Scanning electron microscopy revealed that the chitosan/sodium β-glycerophosphate thermosensitive injectable hydrogel exhibited a typical three-dimensional porous network morphology with uniform pore size distribution and interconnected pores. The curcumin-loaded chitosan/sodium β-glycerophosphate thermosensitive injectable hydrogel exhibited excellent drug sustained-release capacity. Live-dead and skeleton staining revealed that both hydrogels had good cytocompatibility. (3) The degree of peritendinous adhesion in the drug-loaded hydrogel group was lower than that in the model group, the simple hydrogel group, and the drug group. Hematoxylin-eosin and Masson staining revealed reduced inflammatory cell infiltration and orderly collagen deposition in the Achilles tendon tissue of the drug-loaded hydrogel group, indicating improved tissue repair quality. Immunohistochemical staining revealed lower cyclooxygenase-2 protein expression in the drug-loaded hydrogel group compared with the model group, the simple hydrogel group, and the drug group (P < 0.05), while higher expression of type I collagen α1 chain protein was observed in the drug-loaded hydrogel group compared with the model group, the simple hydrogel group, and the drug group (P < 0.05). The maximum tensile stress and elastic modulus in the drug-loaded hydrogel group were higher than those in the model group, the simple hydrogel group, and the drug group (P < 0.05). These results indicate that the curcumin-loaded chitosan/sodium β-glycerophosphate thermosensitive hydrogel synergistically reduces inflammation and promotes orderly collagen deposition, significantly improving the quality of tendon repair.
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    Construction and performance evaluation of pre-vascularized three-dimensional porous bioprinted hydrogel
    Chen Qiyu, Yang Yang, Yuan Changyong, Wang Wen
    2026, 30 (26):  6790-6797.  doi: 10.12307/2026.841
    Abstract ( 50 )   PDF (18276KB) ( 47 )   Save
    BACKGROUND: Three-dimensional bioprinted hydrogels have become an important research direction for the repair of oral tissue defects. Pre-vascularization of hydrogels can be achieved by loading endothelial cells and stromal cells. However, the dense hydrogel fibers often limit cell viability and extension. Whether increasing the internal porosity of the hydrogel can improve pre-vascularization remains unclear.
    OBJECTIVE: To construct porous three-dimensional bioprinted hydrogels loaded with human umbilical vein endothelial cells and human dental pulp stem cells, and to explore the relationship between hydrogel pore size and pre-vascularization.
    METHODS: (1) Methacrylate gelatin solution and poly (ethylene oxide) solution were mixed at volume ratios of 2:1, 1:1, 1:1.5, 1:2, and 1:3, with pure methacrylate gelatin solution as a control. Three-dimensional bioprinting was performed, and after curing and crosslinking, poly (ethylene oxide) was leached out to form pores. Based on porosity measurements, the mixed solutions with methacrylate gelatin solution and poly (ethylene oxide) solution volume ratios of 1:1, 1:2, and 1:3, along with the pure methacrylate gelatin solution, were selected for subsequent experiments. (2) The four types of solutions mentioned above were used as bioinks, separately encapsulating human umbilical vein endothelial cells or human dental pulp stem cells for three-dimensional bioprinting. After curing and crosslinking, poly (ethylene oxide) was leached out to form pores. Live/dead staining was used to detect cell viability. Simultaneously, both cell types were encapsulated and three-dimensional bioprinting was performed. After curing and crosslinking, poly (ethylene oxide) was leached out to form pores, and a tube formation assay was used to detect vascular network formation. (3) The four groups of three-dimensional bioprinted hydrogels, with or without the two cell types, were implanted subcutaneously into CB17-SCID mice. After 14 days, samples were collected, and hematoxylin-eosin staining and CD31 immunohistochemical staining were performed to observe vascular formation within the hydrogels.
    RESULTS AND CONCLUSION: (1) The hydrogel in the pure methacrylate gelatin group had the smallest pores. As the proportion of poly (ethylene oxide) solution in the bioink increased, the pore size of the hydrogel increased. The group with a 2:1 volume ratio of methacrylate gelatin solution to poly (ethylene oxide) solution had excessively small pores, while the 1:2 and 1:1.5 groups had similar pore sizes. Therefore, the 2:1 and 1:1.5 groups were excluded from subsequent experiments. (2) Live/dead staining showed that human umbilical vein endothelial cells in all four hydrogel groups did not show significant spreading. Human dental pulp stem cells showed significant spreading in the hydrogels with a 1:2 and 1:3 volume ratio of methacrylate gelatin solution to poly (ethylene oxide) solution. There was no significant difference in the survival rate of human umbilical vein endothelial cells or human dental pulp stem cells cultured in the hydrogels for 3 days. The pure methacrylate gelatin group hydrogel showed the least vascular formation, and as the proportion of poly (ethylene oxide) solution in the bioink increased, vascular formation in the three-dimensional bioprinted hydrogel increased, resulting in a denser network structure. (3) Hematoxylin-eosin staining and CD31 immunohistochemical staining showed no vascular formation in the cell-free hydrogels. No vascular formation was observed in the pure methacrylate gelatin group and the 1:1 volume ratio methacrylate gelatin solution to poly (ethylene oxide) solution group containing embedded cells. Significant vascular formation was observed in the other two hydrogel groups. (4) The results indicate that the internal pores of the three-dimensional bioprinted methacrylate gelatin hydrogel can promote the formation of in vitro vascular-like structures by human umbilical vein endothelial cells and human dental pulp stem cells, and promote in vivo vascularization of the hydrogel.
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    Hydrogel loaded with fibroblast exosomes promotes endothelial cell function recovery and diabetic wound healing#br#
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    Zhang Jing, He Liping, Wen Yu, Fu Hang
    2026, 30 (26):  6798-6806.  doi: 10.12307/2026.412
    Abstract ( 48 )   PDF (6794KB) ( 35 )   Save
    BACKGROUND: Exosomes, as an important mediator of intercellular communication, have been widely used in tissue repair and regeneration. Exosome-loaded hydrogels can significantly improve the stability and bioavailability of exosomes, thereby enhancing therapeutic efficacy.
    OBJECTIVE: To investigate the effects of fibroblast-exosome-loaded hydrogels on endothelial cell function recovery and wound repair in diabetic rats.
    METHODS: Exosomes isolated from human skin fibroblasts were added to PF-127 hydrogels to prepare fibroblast-exosome-loaded PF-127 hydrogels. (1) Cellular experiment: A suspension of third-generation human umbilical vein endothelial cells was cultured in four groups: a control group incubated with 5 mmol/L glucose; a high glucose group incubated with 50 mmol/L glucose; a high glucose + hydrogel group incubated with 50 mmol/L glucose and PF-127 hydrogel, and a high glucose + exosome-loaded hydrogel group incubated with 50 mmol/L glucose and exosome-loaded PF-127 hydrogel. Cell proliferation was assessed by EdU staining. Cell migration was assessed by wound healing assay and Transwell assay. Cell angiogenesis was assessed by tube formation assay. Intracellular ferroptosis was assessed by western blot assay and transmission electron microscopy. (2) Animal experiment: Twenty-four SD rats were randomly divided into four intervention groups. The control group (n=6) underwent a 1-cm diameter full-thickness skin defect on the back without any treatment. The diabetes group (n=6) underwent a 1-cm diameter full-thickness skin defect after the establishment of a type 1 diabetes model without any treatment. Type 1 diabetes models were established in the diabetes + hydrogel group (n=6) and the diabetes + exosome-loaded hydrogel group (n=6). A 1-cm diameter full-thickness skin defect was made on the back. PF-127 hydrogel and PF-127 hydrogel loaded with fibroblast exosomes were injected for treatment, respectively. The drugs were administered twice a week for a total of 3 weeks. Wound healing was observed during the treatment period. After the administration, samples were collected and analyzed by hematoxylin-eosin staining and CD31 immunohistochemical staining.
    RESULTS AND CONCLUSION: (1) Cell experiment: High glucose treatment inhibited the proliferation, migration, and tube formation of human umbilical vein endothelial cells, inducing ferroptosis. PF-127 hydrogel loaded with fibroblast exosomes significantly enhanced the proliferation, migration, and tube formation of human umbilical vein endothelial cells treated with high glucose, inhibiting ferroptosis. (2) Animal experiment: The wound closure rate in the diabetes + exosome-loaded hydrogel group was faster than that in the diabetes and diabetes + hydrogel groups. Hematoxylin-eosin staining showed that the wound healing quality in the diabetes group and the diabetes + hydrogel group was poor, while the wound healing quality in the diabetes + exosome-loaded hydrogel group was good, but not as good as that in the control group. CD31 immunohistochemical staining showed that angiogenesis in the wounds in the diabetes group and the diabetes + hydrogel group was less than that in the control group and the diabetes + exosome-loaded hydrogel group. (3) These results indicate that PF-127 hydrogel loaded with fibroblast exosomes accelerates wound repair in diabetic rats by inhibiting ferroptosis and promoting endothelial cell function recovery.
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    Mechanism of ferrostatin-1 hydrogel in treatment of lumbar disc herniation
    Chen Gang, Ge Caijun, Chen Jianpeng, Wang Yuanbin, Wang Qianliang
    2026, 30 (26):  6807-6813.  doi: 10.12307/2026.802
    Abstract ( 40 )   PDF (1570KB) ( 15 )   Save
    BACKGROUND: Targeting the molecular mechanisms of ferrostatin, intervening in iron metabolism or inhibiting lipid peroxidation is expected to be a new strategy for the treatment of lumbar disc herniation, providing a new research direction for disease prevention and treatment.
    OBJECTIVE: To investigate the mechanism of action of the ferroptosis inhibitor ferrostatin-1 on lumbar disc herniation through in vitro cell experiments and in vivo animal studies using poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid) hydrogel as a carrier.
    METHODS: (1) Third-generation mouse nucleus pulposus cells were divided into three treatment groups: the control group received no treatment; the model group received 10 ng/mL interleukin-1β, and the ferrostatin-1 group received 10 ng/mL interleukin-1β plus 25 μmol/L ferrostatin-1. Intracellular malondialdehyde levels, glutathione levels, iron ion content, and the mRNA expression of extracellular matrix-related genes type II collagen, aggrecan, and matrix metalloproteinase-3 were measured. (2) A poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid) hydrogel loaded with ferrostatin 1 (drug-loaded hydrogel) was prepared and characterized for its micromorphology and in vitro drug release. Eighty C57BL/6 mice were randomly divided into a normal group, a model group, a free drug group, and a drug-loaded hydrogel group, with 20 mice in each group. A L5/6 lumbar disc herniation model was established in the remaining three groups, except the normal group. PBS, ferrostatin 1 solution, and drug-loaded hydrogel were injected into the paravertebral tissue of the model group, free drug group, and drug-loaded hydrogel group, respectively. Mechanical and thermal pain thresholds of the mice in each group were dynamically monitored. On the seventh day of drug administration, nucleus pulposus tissue was extracted and levels of inflammatory factors (tumor necrosis factor α and interleukin 1β), malondialdehyde, and glutathione were measured, as well as the mRNA expression of ferroptosis pathway-related genes, glutathione peroxidase 4 and solute carrier family 7 member 11.
    RESULTS AND CONCLUSION: (1) Compared with the control group, the model group showed increased intracellular malondialdehyde levels, intracellular iron accumulation, and matrix metalloproteinase-3 mRNA expression (P < 0.05), while decreased glutathione levels and mRNA expression of type II collagen and aggrecan (P < 0.05). Compared with the model group, the ferrostatin 1 group showed decreased intracellular malondialdehyde levels, intracellular iron accumulation, and mRNA expression of matrix metalloproteinase-3 (P < 0.05), while increased glutathione levels and mRNA expression of type II collagen and aggrecan (P < 0.05). (2) Scanning electron microscopy revealed a loose, porous structure containing vacuoles of varying sizes, indicating that the hydrogel exhibited good sustained-release drug properties. Compared with the model group, both the free drug group and the drug-loaded hydrogel group showed pain relief, decreased levels of inflammatory factors and malondialdehyde (P < 0.05), and increased glutathione levels and mRNA expressions of glutathione peroxidase 4 and solute carrier family 7 member 11 (P < 0.05). The drug-loaded hydrogel exhibited a stronger effect than the free drug. (3) The results suggest that ferrostatin 1 protects nucleus pulposus cells by regulating the expression of genes related to oxidative stress and ferroptosis, treating lumbar disc herniation in mice.
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    Sr/birabresib-loaded bioactive glass modulating bone microenvironment for osteoporosis therapy
    Zhao Wenbo, Miao Xin, Wang Yang, Liu Hao, Li Shengfa, Tao Qifeng
    2026, 30 (26):  6814-6825.  doi: 10.12307/2026.760
    Abstract ( 31 )   PDF (6734KB) ( 97 )   Save
    BACKGROUND: Existing treatments can effectively reduce fracture risk in patients with osteoporosis, but their effectiveness is limited in patients with concurrent inflammatory diseases (such as rheumatoid arthritis) or severe postmenopausal osteoporosis. Therefore, the development of novel therapeutic strategies with both anti-inflammatory and anti-osteoclast properties is of great clinical significance.  
    OBJECTIVE: To develop an innovative Sr²⁺ and bromodomain inhibitor Birabresib-loaded nanocomposite material (Bir@Sr-MBG) and characterize their cytocompatibility and in vitro immunomodulatory, anti-osteoclast differentiation, and osteoclast differentiation-promoting effects. 
    METHODS: (1) Strontium-bioactive glass (Sr-MBG) was synthesized using a modified microemulsion-assisted sol-gel method. Birabresib was loaded into the mesoporous structure of Sr-MBG using an optimized solution adsorption method. The resulting material, designated Bir@Sr-MBG, was characterized for drug encapsulation efficiency, drug loading rate, and in vitro drug release. (2) Primary mouse bone marrow macrophages were cultured with different concentrations of birabresib or Bir@Sr-MBG, and cytocompatibility was assessed using the CCK-8 assay. (3) Primary mouse bone marrow macrophages were divided into five intervention groups: the control group received no intervention; the lipopolysaccharide group received lipopolysaccharide (to induce an inflammatory model); the Sr-MBG group received lipopolysaccharide + 10 mg/mL Sr-MBG; the birabresib group received lipopolysaccharide + 10 mg/mL birabresib, and the Bir@Sr-MBG group received lipopolysaccharide + 10 mg/mL Bir@Sr-MBG. After 24 hours of incubation, the expression levels of inducible nitric oxide synthase (a marker of M1 macrophages) and CD206 (a marker of M2 macrophages) were detected by immunofluorescence staining. The mRNA expression levels of interleukin-1β, interleukin-6, tumor necrosis factor-α, and interleukin-4 were detected by qPCR. The levels of interleukin-1β, interleukin-6, tumor necrosis factor-α, and interleukin-4 in the cell supernatant were detected by ELISA. (4) After osteoclastogenesis induction, primary mouse bone marrow macrophages were divided into four intervention groups: the control group received no intervention; the Sr-MBG group received 5 mg/mL Sr-MBG; the birabresib group received 0.5 mg/mL birabresib, and the Bir@Sr-MBG group received 5 mg/mL Bir@Sr-MBG. After 5 days of intervention, tartrate-resistant acid phosphatase staining and cytoskeleton staining were performed, followed by scanning electron microscopy observation. qPCR was used to measure the mRNA expression of osteoclastogenesis-related genes (cathepsin K, proto-oncogene Fos, tartrate-resistant acid phosphatase, and activated T-cell nuclear factor 1). (5) Adherent rat bone marrow mesenchymal stem cells were cultured in osteogenic induction medium and divided into five intervention groups: the control group received no intervention; the lipopolysaccharide group received lipopolysaccharide; the Sr-MBG group received lipopolysaccharide plus 10 mg/mL Sr-MBG; the birabresib group received lipopolysaccharide plus 0.5 mg/mL birabresib, and the Bir@Sr-MBG group received lipopolysaccharide plus 10 mg/mL Bir@Sr-MBG. On day 7 of culture, cells were stained with alkaline phosphatase and Alizarin red. qPCR was used to analyze the mRNA expression of osteogenic-related genes (alkaline phosphatase, RUNT-related transcription factor 2, osteocalcin, and osteopontin). 
    RESULTS AND CONCLUSION: (1) The drug encapsulation efficiency and drug loading efficiency of Bir@Sr-MBG were 44.82% and 7.47%, respectively. Bir@Sr-MBG sustainedly released birabresib for over 168 hours. (2) CCK-8 assays showed that both 0.1–1 μg/mL birabresib and 20–200 μg/mL Bir@Sr-MBG exhibited good cytocompatibility. (3) Immunofluorescence staining revealed that Bir@Sr-MBG improved the inflammatory microenvironment by regulating macrophage polarization, and the material exhibited stronger anti-inflammatory properties than Sr-MBG and birabresib. qPCR and ELISA revealed that Bir@Sr-MBG downregulated the expression of proinflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-α) and upregulated the expression of anti-inflammatory cytokines (interleukin-4) more than Sr-MBG and birabresib. (4) Tartrate-resistant acid phosphatase staining, cytoskeleton staining, scanning electron microscopy, and qPCR revealed that Bir@Sr-MBG exhibited a stronger ability to inhibit osteoclast differentiation than Sr-MBG and birabresib. (5) Alkaline phosphatase staining, Alizarin red staining, and qPCR revealed that under inflammatory conditions, Bir@Sr-MBG promoted osteogenic differentiation of rat bone marrow mesenchymal stem cells more effectively than Sr-MBG and birabresib. (6) These results suggest that Bir@Sr-MBG effectively regulates bone metabolism and improves the bone microenvironment through a dual mechanism of action, demonstrating significant therapeutic potential for osteoporosis. 
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    Quantitative analysis of bone cement dispersion height and efficacy comparison in percutaneous vertebroplasty and percutaneous kyphoplasty
    Ma Zaichao, Maimaitiyibubaji·Abudukadier, Yang Zengqiang, Li Biao, Zhang Zheng, Cui Yong
    2026, 30 (26):  6826-6832.  doi: 10.12307/2026.762
    Abstract ( 20 )   PDF (2339KB) ( 8 )   Save
    BACKGROUND: Studies have shown that patients with osteoporotic vertebral compression fractures exhibit significant individual differences in prognostic outcomes. The underlying mechanisms are closely associated with the choice of surgical technique, the distribution characteristics of bone cement within the vertebral body, and the degree of height restoration of the injured vertebra.
    OBJECTIVE: To explore the difference in bone cement dispersion height between percutaneous vertebroplasty and percutaneous kyphoplasty in the treatment of osteoporotic vertebral compression fractures.
    METHODS: A total of 112 patients with single-segment osteoporotic vertebral compression fractures admitted to the Fifth Affiliated Hospital of Xinjiang Medical University from May 2019 to February 2025 were included. They were divided into a percutaneous vertebroplasty group (n=57) and a percutaneous kyphoplasty group (n=55) based on the surgical procedure. The visual analog scale score, Oswestry Disability Index, local kyphotic angle of the injured vertebra, and complication rates were compared between the two groups at 6 months postoperatively. The bone cement dispersion heights in the anterior and middle columns of the vertebral body, as well as the maximum dispersion height, were also compared between the two groups. Pearson correlation analysis was used to evaluate the relationship between bone cement dispersion height and the Oswestry Disability Index at 6 months after surgery.
    RESULTS AND CONCLUSION: (1) At 6 months postoperatively, the visual analog scale score, Oswestry Disability Index, and local kyphotic angle were significantly lower than preoperative values in both groups (P < 0.05). At 6 months after surgery, the percutaneous kyphoplasty group showed significantly lower visual analog scale scores, Oswestry Disability Index, and local kyphotic angle compared with the percutaneous vertebroplasty group (P < 0.05). There was no significant difference in the rates of bone cement leakage or adjacent vertebral fracture between the two groups (P > 0.05). (2) The bone cement dispersion heights in the anterior and middle columns, as well as the maximum dispersion height, were significantly greater in the percutaneous kyphoplasty group than in the percutaneous vertebroplasty group (P < 0.05). (3) Pearson correlation analysis revealed a significant negative correlation between the anterior column bone cement dispersion height (and maximum dispersion height) and the Oswestry Disability Index at 6 months postoperatively (r=-0.730, P < 0.001; r=-0.700, P < 0.001; r=-0.581, P < 0.001; r=-0.468, P < 0.001). No significant correlation was found between the middle column bone cement dispersion height and the Oswestry Disability Index at 6 months postoperatively (r=-0.089, P < 0.520; r=-0.024, P < 0.859). (4) The results indicate that the three-dimensional dispersion height of bone cement within the vertebral body can serve as a potential imaging predictor for evaluating the efficacy of percutaneous vertebroplasty and percutaneous kyphoplasty. 
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    Physicochemical properties and angiogenesis-promoting effects of copper-containing calcium sulfate bone cement
    Huang Lei, Lan Tian, ​​Zeng Hui
    2026, 30 (26):  6833-6839.  doi: 10.12307/2026.232
    Abstract ( 29 )   PDF (4902KB) ( 10 )   Save
    BACKGROUND: Calcium sulfate has been widely used as a bone graft for the treatment of alveolar bone loss, endodontic lesions, and periodontal disease. Copper plays an important role in various biological processes, including angiogenesis and cell migration.
    OBJECTIVE: To prepare copper-containing calcium sulfate bone cement and characterize its physicochemical properties and angiogenesis.
    METHODS: (1) Calcium sulfate hemihydrate was used as the solid phase and copper sulfate pentahydrate solutions of varying concentrations were used as the liquid phase. The solid and liquid phases were mixed at a ratio of 1.7 g/1 mL. The mass ratios of copper sulfate pentahydrate to calcium sulfate hemihydrate were 0.1%, 0.5%, 1%, and 2.5%, respectively. The prepared copper-containing calcium sulfate bone cements were designated 0.1%Cu-CS, 0.5%Cu-CS, 1%Cu-CS, and 2.5%Cu-CS, respectively. Pure calcium sulfate bone cement was also prepared. The micromorphology, compressive strength, and copper and calcium ion release in the in vitro degradation solution of the five cements were characterized. (2) Thirty SD rats selected and a single cortical bone defect model with a diameter of 3 mm and a length of 5 mm was established on the left tibia. These models were randomly divided into three groups: a blank group (n=10) received no intervention; a control group (n=10) received calcium sulfate bone cement implantation; and an experimental group (n=10) received 0.5% Cu-CS bone cement implantation. Six weeks after surgery, angiogenesis at the tibial defect site was observed using micro-CT scans and CD31 immunohistochemical staining after vascular microfil perfusion.
    RESULTS AND CONCLUSION: (1) Scanning electron microscopy revealed rod-shaped calcium sulfate crystals on the surface of calcium sulfate cement and plate-like gypsum crystals on the surface of copper-containing calcium sulfate cement. The number of plate-like gypsum crystals increased with increasing copper sulfate pentahydrate mass. The compressive strengths of 0.5% Cu-CS and 1% Cu-CS bone cements were higher than those of calcium sulfate and 0.1% Cu-CS bone cements (P < 0.05), and the compressive strength of 2.5% Cu-CS bone cement was higher than that of 0.5% Cu-CS and 1% Cu-CS bone cements (P < 0.05). After immersion in simulated body fluid for 6 weeks, calcium sulfate bone cement released the highest calcium ion concentration, while 2.5% Cu-CS bone cement released the lowest. Calcium sulfate bone cements did not release copper ions. Among copper-containing calcium sulfate bone cements, 2.5% Cu-CS bone cement released the highest copper ion concentration, while 0.1% Cu-CS bone cement released the lowest. (2) Micro-CT scanning showed that the blank group had the least neovascularization within the bone defect, while the experimental group had the most neovascularization within the bone defect. CD31 immunohistochemical staining revealed that only punctate or linear neovascular structures were observed in the bone defect of the blank and control groups, while the experimental group had abundant and dense blood vessel formation. (3) The results confirm that copper-containing calcium sulfate bone cement has excellent mechanical properties and sustained copper ion release, promoting angiogenesis.
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    Preparation and biocompatibility of odanacatib microspheres-gel composite sustained-release carrier 
    Lyu Tianyang, Li Ning, Huang Shuo, Liu Changkui, Guo Yayuan, Hu Kaijin
    2026, 30 (26):  6840-6848.  doi: 10.12307/2026.761
    Abstract ( 26 )   PDF (9264KB) ( 16 )   Save
    BACKGROUND: Odanacatib effectively exerts anti-inflammatory effects and promotes alveolar bone repair in periodontitis-affected areas. However, multiple injections are required to ensure efficacy, which is cumbersome. 
    OBJECTIVE: To prepare an odanacatib-loaded microsphere-gel composite sustained-release carrier and characterize its biocompatibility.  
    METHODS: (1) Poly(lactic-co-glycolic acid) microspheres (ODN-MS) loaded with varying amounts of odanacatib were prepared by an emulsification-solvent evaporation method. Microspheres prepared with 5 mg of odanacatib and 40 mg of poly(lactic-co-glycolic acid) were selected for subsequent experiments based on drug loading and encapsulation efficiency. A gel composite sustained-release carrier (ODN-MS-Gel) was prepared by mixing varying amounts of ODN-MS with a gelatin methacryloyl solution. The ODN-MS mass concentrations were 250 and 500 μg/mL, respectively. The micromorphology and in vitro drug release properties of the ODN-MS and 250 μg/mL ODN-MS-Gel were characterized. (2) Rabbit bone marrow mesenchymal stem cells were cultured using extracts of gelatin methacryloyl gel, extracts of a composite sustained-release carrier loaded with poly(lactic-co-glycolic acid) microspheres, and extracts of 250 and 500 μg/mL ODN-MS-Gel, respectively. Cell proliferation was assessed by CCK-8 assay. Rabbit bone marrow mesenchymal stem cells were cultured using extracts of gelatin methacryloyl gel, extracts of a composite sustained-release carrier loaded with poly(lactic-co-glycolic acid) microspheres, and extracts of 250 μg/mL ODN-MS-Gel, respectively. Cell viability was assessed by live/dead staining. Rabbit bone marrow mesenchymal stem cells were seeded onto gelatin methacryloyl gel, a composite sustained-release carrier loaded with poly(lactic-co-glycolic acid) microspheres, and 250 μg/mL ODN-MS-Gel, respectively. Cell adhesion was observed by phalloidin staining and scanning electron microscopy.
    RESULTS AND CONCLUSION: (1) Optical microscopy revealed that the ODN-MS was spherical, uniformly distributed, and free of agglomerates. Scanning electron microscopy revealed a fine porous structure on the surface of ODN-MS. The 250 μg/mL ODN-MS-Gel hydrogel exhibited a porous structure, with ODN-MS distributed throughout the hydrogel's porous structure. Both ODN-MS and 250 μg/mL ODN-MS-Gel achieved sustained drug release, with the 250 μg/mL ODN-MS-Gel system exhibiting a more gradual release, demonstrating a dual sustained-release effect. (2) CCK-8 assay revealed that the 250 and 500 μg/mL ODN-MS-Gel extracts promoted the proliferation of rabbit bone marrow mesenchymal stem cells. Live/dead staining revealed that the 250 μg/mL ODN-MS-Gel extract did not affect the viability of rabbit bone marrow mesenchymal stem cells. Phalloidin staining and scanning electron microscopy revealed that the 250 μg/mL ODN-MS-Gel promoted the adhesion of rabbit bone marrow mesenchymal stem cells compared with the other two materials. The results verify that ODN-MS-Gel can achieve sustained release of odanacatib and has good biocompatibility.
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    Preparation of recombinant humanized type III collagen and its structural characterization and safety evaluation
    Qi Lei, Wu Feitao, Yu Yuexin, Dai Chaomei, Song Fu, Bian Yinbo, Xu Lanju
    2026, 30 (26):  6849-6858.  doi: 10.12307/2026.843
    Abstract ( 85 )   PDF (5183KB) ( 33 )   Save
    BACKGROUND: Recombinant collagen can avoid the risk of viral transmission associated with animal-derived collagen and has good water solubility and excellent biological properties. It holds broad application prospects in medical, cosmetic, and food fields. However, there is a lack of systematic reports on strain construction, production process, structural characterization, quality research, and safety evaluation.
    OBJECTIVE: To construct a high-yield strain of recombinant humanized type III collagen, establish fermentation and purification processes, and characterize and evaluate the safety of the purified product.
    METHODS: A recombinant humanized type III collagen-expressing Escherichia coli strain was constructed. High-density fermentation was used to achieve high expression of the target protein. The target protein — recombinant humanized type III collagen — was extracted using immobilized metal affinity chromatography and ion exchange chromatography. The impurity residue and structure of the recombinant humanized type III collagen were analyzed by quantitative PCR, ELISA, ultra high performance liquid chromatography-mass spectrometry, and differential scanning calorimetry. The safety of the recombinant humanized type III collagen was evaluated through intradermal reaction tests, skin sensitization tests, acute systemic toxicity tests, and cell proliferation and migration experiments.
    RESULTS AND CONCLUSION: The recombinant humanized type III collagen high-yield strain constructed in this study achieved a yield of 10 g/L in a 5-L fermenter. The peptide coverage and molecular weight analysis of the purified recombinant humanized type III collagen showed that the expressed product was completely consistent with the designed sequence. The melting temperature value of the purified product was 79.72°C, which was significantly higher than body temperature. The residual exogenous DNA, Escherichia coli protein, and endotoxin in the purified product all met the standard requirements. Intradermal reactivity tests, skin sensitization tests, acute systemic toxicity tests, and cell proliferation and migration experiments have exhibited that the recombinant humanized type III collagen product has good safety.

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    Biocompatibility and preclinical experiments of a Chinese-made 3D-printed minimally invasive tungsten alloy needle electrodes
    Li Yujin, Ni Guansen, Mao Weiqing, Tang Jiayu, Li Xueqing
    2026, 30 (26):  6859-6867.  doi: 10.12307/2026.382
    Abstract ( 55 )   PDF (2119KB) ( 13 )   Save
    BACKGROUND: The increasing prevalence of minimally invasive surgery has placed higher demands on high-frequency electrosurgical equipment. Imported minimally invasive tungsten alloy electrodes offer high cutting precision, low tissue adhesion, and good biocompatibility, but their high cost limits their widespread application. Therefore, conducting biocompatibility and preclinical animal studies on Chinese-made 3D-printed minimally invasive tungsten alloy needle electrodes can provide a scientific basis for the research and development of Chinese-made minimally invasive electrodes. 
    OBJECTIVE: To evaluate the biocompatibility and preclinical safety of Chinese-made 3D-printed tungsten alloy needle-shaped electrodes. 
    METHODS: (1) Biocompatibility: L-929 cells were co-cultured with extracts from Chinese-made 3D-printed minimally invasive tungsten alloy needle electrodes at different concentrations (100%, 50%, 25%, and 12.5%), and the cytotoxicity of the materials was assessed using the MTT assay. Intradermal stimulation experiments were performed on New Zealand white rabbits to evaluate the skin irritation of the Chinese-made 3D-printed minimally invasive tungsten alloy needle electrodes. Sensitization experiments were performed on albino guinea pigs to evaluate the skin allergic reaction of the Chinese-made 3D-printed minimally invasive tungsten alloy needle electrodes. (2) Preclinical animal experiments: Thirty-six SD rats were randomly divided into a 304 stainless steel electrode group (n=12), an imported minimally invasive tungsten alloy needle electrode group (n=12), and a Chinese-made 3D-printed minimally invasive tungsten alloy needle electrode group (n=12). The corresponding electrodes were used to incise the abdominal subcutaneous tissue and abdominal wall muscle layer. The incisions were sutured, and the amount of adhesion on the electrode surface, intraoperative blood loss, and smoke formation were recorded. Fourteen days after surgery, wound healing, fat liquefaction, and incision histological morphology were observed. 
    RESULTS AND CONCLUSION: (1) MTT assays showed that the cell survival rate in the extracts from the Chinese-made 3D-printed minimally invasive tungsten alloy needle electrode groups was above 80%, with no significant cytotoxicity. Intradermal stimulation and sensitization experiments showed that the Chinese-made 3D-printed minimally invasive tungsten alloy needle electrodes did not cause significant skin irritation or allergic reactions. (2) Compared with the 304 stainless steel electrode group, the Chinese-made 3D-printed minimally invasive tungsten alloy needle electrode group showed reduced surface adhesion mass and increased intraoperative bleeding and smoke formation (P < 0.05). There were no significant differences in surface adhesion mass, intraoperative bleeding, or smoke formation between the Chinese-made and imported 3D-printed minimally invasive tungsten alloy needle electrode groups (P > 0.05). There were no significant differences in wound healing, fat liquefaction, or adverse wound reactions among the three groups (P > 0.05). Hematoxylin-eosin staining revealed mild inflammatory cell infiltration in the incision tissues of all three groups, consistent with the normal pathological process of wound repair. No abnormal immune response or delayed healing was observed. (3) These results demonstrate that the Chinese-made 3D-printed minimally invasive tungsten alloy needle electrodes exhibit excellent biocompatibility and safety, and their overall performance is comparable to that of imported tungsten needle electrodes.
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    Apical sealing and resistance strength of C-Root BP material in in vitro environment
    Zhou Lijing, Wang Shuang, Xiang Jinjiao, Wang Huichao, Chai Xuejiao
    2026, 30 (26):  6868-6872.  doi: 10.12307/2026.209
    Abstract ( 47 )   PDF (1297KB) ( 21 )   Save
    BACKGROUND: In recent years, bioceramic materials have become the preferred materials for retrograde apical filling due to their excellent biocompatibility and sealing properties. The bioceramic materials C-Root BP and iRoot BP Plus both exhibit excellent biocompatibility and sealing properties.
    OBJECTIVE: To compare the apical sealing performance and resistance strength of C-Root BP and iRoot BP Plus materials in vitro. 
    METHODS: From June 2022 to June 2024, 56 freshly extracted single detached teeth at the Department of Stomatology, Shijiazhuang Second Hospital due to orthodontics or periodontal disease were collected and randomly divided into four groups. The iRoot BP Plus group (n=16) and C-Root BP group (n=16) were respectively treated with iRoot BP Plus and C-Root BP materials for root tip filling. The positive control group (n=16) was treated with distilled water for root tip filling, while the negative control group (n=8) was not treated with root tip filling and only underwent routine root canal preparation and disinfection. Dye penetration method was used to detect the apical sealing. A root canal bacterial leakage model was made in vitro, and bacterial microleakage was evaluated. The adhesion strength between the filling material and dentin was measured by wafer extrusion test, and the fracture form was observed under a microscope. 
    RESULTS AND CONCLUSION: (1) After 7 days of dye staining, the dye penetration length of the positive control group was greater than that of the iRoot BP Plus group and C-Root BP group (P < 0.05). There was no significant difference in dye penetration length between the iRoot BP Plus group and the C-Root BP group (P > 0.05). (2) After 90 days of cultivation, the incidence of bacterial microleakage in the positive control group was higher than that in the iRoot BP Plus group and C-Root BP group (P < 0.05), while there was no significant difference in the incidence of bacterial microleakage between the iRoot BP Plus group and C-Root BP group (P > 0.05). (3) The adhesion strength between the filling material and dentin in the C-Root BP group was greater than that in the iRoot BP Plus group (P < 0.05), and there was no significant difference in the fracture surface pattern between the two groups (P > 0.05). (4) These findings indicate that the use of C-Root BP and iRoot BP Plus materials for root tip filling can produce similar root tip sealing effects, and the fracture mode is also basically the same. However, C-Root BP material has good adhesion strength.

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    Ready-to-use sodium alginate@paper material for three-dimensional cell culture
    Yu Jinye, Jiang Nan, Zhao Yixun, Huang Mengjing, Yang Jie, Sun Rui, Feng Suolan, Jiang Hui, Yang Jun
    2026, 30 (26):  6873-6879.  doi: 10.12307/2026.113
    Abstract ( 33 )   PDF (3393KB) ( 26 )   Save
    BACKGROUND: Cells-in-gels-in-paper (CiGiP) is a three-dimensional cell culture technique that uses hydrogels to encapsulate cells within paper fibers. It offers a promising approach for the development of three-dimensional cell culture. However, the hydrogels must be prepared in advance and then added to the paper material, which lacks certain convenience and hinders the widespread application of CiGiP.
    OBJECTIVE: To prepare a ready-to-use sodium alginate@paper material and to analyze its application in three-dimensional cell culture.
    METHODS: (1) 2% sodium alginate was incorporated into paper materials, allowing it to evenly penetrate the paper material to obtain a ready-to-use sodium alginate@paper material. A mixture of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide was then dripped onto the ready-to-use sodium alginate@paper material. Polyethylene glycol-diamine at different concentrations (5%, 10%, 15%, and 20%) was then added dropwise. The prepared sodium alginate@paper material was freeze-dried to obtain the ready-to-use sodium alginate@paper material. 15% polyethylene glycol-diamine was selected based on swelling ratio for subsequent preparation of ready-to-use sodium alginate@paper materials. (2) Human embryonic kidney (HEK) 293 cells were co-cultured with the ready-to-use sodium alginate@paper materials. Cells cultured alone were used as controls. The cytotoxicity of the ready-to-use sodium alginate@paper materials was assessed by lactate dehydrogenase release assay. HEK 293 cells labeled with SYTOTM 9 green fluorescent nucleic acid dye were plated onto the ready-to-use sodium alginate@paper materials and freshly prepared alginate@paper materials, and cell adhesion was observed under laser confocal microscopy and scanning electron microscopy. (3) The ready-to-use sodium alginate@paper materials were stored in clean culture dishes at room temperature for 0, 40, 80, and 120 days, and the micromorphology and porosity of the materials were examined. HEK 293 cells were seeded to ready-to-use sodium alginate@paper materials after storage for 0, 40, 80, and 120 days and the cytotoxicity of the ready-to-use sodium alginate@paper materials was assessed by lactate dehydrogenase release assay. HEK 293 cells labeled with SYTOTM 9 green fluorescent nucleic acid dye were seeded onto ready-to-use sodium alginate@paper materials after storage for 0, 40, 80, and 120 days, and cell adhesion was observed under laser confocal microscopy.
    RESULTS AND CONCLUSION: (1) Lactate dehydrogenase release assays demonstrated that the ready-to-use sodium alginate@paper materials were non-cytotoxic. Laser confocal microscopy revealed that HEK 293 cells adhered uniformly to both materials, with no significant difference in adhesion between the two groups. Scanning electron microscopy revealed that HEK 293 cells maintained cell-cell interactions in both materials, with no significant difference between the two groups. (2) After 120 days of storage, the sodium alginate hydrogel in the ready-to-use sodium alginate@paper materials did not detach from the paper fibers, and the porosity did not change significantly. Lactate dehydrogenase release assays demonstrated that the ready-to-use sodium alginate@paper materials were non-cytotoxic after storage for 40, 80, and 120 days. Laser confocal microscopy revealed that HEK 293 cells adhered uniformly to the ready-to-use sodium alginate@paper material after storage for 40, 80, and 120 days, with no significant difference in adhesion compared with unstored ready-to-use sodium alginate@paper. These results demonstrate the excellent stability of the ready-to-use sodium alginate@paper material.
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    Biocompatibility evaluation of polylactic acid/collagen electrospinning bilayer guided tissue regeneration membrane
    Song Muze, Liu Chuyi, , Tang Qingjuan, Dai Yuankun, , Song Wenshan, Li Bafang, Wang Yuanyuan
    2026, 30 (26):  6880-6891.  doi: 10.12307/2026.401
    Abstract ( 47 )   PDF (3032KB) ( 47 )   Save
    BACKGROUND: Marine collagen can promote the proliferation and differentiation of periodontal ligament fibroblasts and the proliferation of vascular endothelial cells. However, simple collagen membranes have low mechanical strength and rapid degradation, necessitating composite materials. Polylactic acid, a biodegradable medical material approved by the US Food and Drug Administration for implantation, can be composited with collagen to improve the mechanical strength of simple collagen.
    OBJECTIVE: To prepare a polylactic acid/collagen electrospinning bilayer guided tissue regeneration membrane and investigate its biocompatibility. 
    METHODS: A 7% polylactic acid solution was used as the spinning dope for the dense layer and a 14% polylactic acid-collagen solution was used as the spinning dope for the loose layer. The polylactic acid/collagen double-layer guided tissue regeneration membrane was prepared by electrospinning technology. The membranes were characterized for micromorphology, pore size, and porosity. The membranes were cross-linked using three methods: glutaraldehyde vapor, glutaraldehyde solution, and carbodiimide/hydroxysuccinimide. Tensile tests were performed to identify the membranes with the best mechanical properties for subsequent experiments. The hydrophilic and hydrophobic properties of the polylactic acid/collagen bilayer guided tissue regeneration membrane were evaluated by characterizing water contact angles. The biocompatibility of the polylactic acid/collagen bilayer guided tissue regeneration membrane was evaluated by cytotoxicity, pyrogen, hemolysis, acute systemic toxicity, subchronic systemic toxicity, sensitization, and intradermal stimulation tests.
    RESULTS AND CONCLUSION: The fiber diameter of the dense layer of the collagen/polylactic acid electrospinning bilayer guided tissue regeneration membrane was (0.45±0.11) μm, and the fiber diameter of the loose layer was (0.85±0.19) μm. The pore size of the dense layer was (2.43±1.31) μm, with a porosity of (29.86±2.89)%, while the pore size of the loose layer was (11.71±4.41) μm, with a porosity of (48.54±1.33)%. Based on the tensile strength, elastic modulus, and elongation at break results from the tensile test, glutaraldehyde vapor crosslinking was ultimately selected for crosslinking, achieving a crosslinking degree of (17.42±1.67)%. The loose layer of the polylactic acid/collagen bilayer guided tissue regeneration membrane exhibited hydrophilicity, while the dense layer was hydrophobic. The polylactic acid/collagen electrospinning bilayer guided tissue regeneration membrane was non-cytotoxic, non-hemolytic, non-pyrogenic, non-potentially toxic, non-irritating, and non-sensitizing, demonstrating excellent biocompatibility.
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    Degradation characteristics and biotoxicity of new domestic polyglycolic acid neural catheter
    Xu Shenglai, Guan Xingqi, Sun Haiwei, Bai Zeming, Guo Bingyu, Tao Kai
    2026, 30 (26):  6892-6898.  doi: 10.12307/2026.253
    Abstract ( 31 )   PDF (3933KB) ( 18 )   Save
    BACKGROUND: Neural catheterization repair of peripheral nerve defects is a research hotspot in the field of biomedical engineering, but the autologous nerve graft repair method as the gold standard has limitations, so there is an urgent need for a method that can replace autologous nerve grafting to repair peripheral nerve defects.
    OBJECTIVE: To observe the degradation characteristics and biological toxicity of the new domestic polyglycolic acid neural catheters.
    METHODS: (1) Degradation performance: PBS was added to the test tubes of the blank control group. PBS and new domestic polyglycolic acid neural catheter were added to the test tubes of the fluid exchange group, with PBS changed every 3 days. PBS and the new domestic polyglycolic acid neural catheter were added to the test tubes of the non-fluid exchange group, without changing the fluid. All three groups of test tubes were placed in a 37℃ incubator, and the pH value of the fluid in the test tubes was checked weekly. (2) Cell experiments: Human fibroblasts were cultured in two groups: the control group received simple culture medium, and the experimental group received culture medium containing an extract of the new domestic polyglycolic acid neural catheter. Cell compatibility of the nerve conduit was assessed by cell morphology, CCK-8 assay, scratch assay, and Transwell assay. (3) In vivo histocompatibility: The new domestic polyglycolic acid neural catheter and the imported neural catheter were implanted between the biceps femoris and gluteus maximus muscles of SD rats, respectively, to evaluate the degradation characteristics and biotoxicity of the neural catheters. 
    RESULTS AND CONCLUSION: (1) In vitro degradation experiments showed that, with fluid exchange, the degradation of the new domestic polyglycolic acid neural catheter had little effect on the pH of the surrounding fluid. Without fluid exchange, the degradation of the new domestic polyglycolic acid neural catheter lowered the pH of the surrounding fluid. (2) Cells in both groups showed good growth, with normal cell morphology and volume. CCK-8 assay showed that the new domestic polyglycolic acid neural catheter did not affect the proliferation of human fibroblasts. Scratch and Transwell assays showed that the new domestic polyglycolic acid neural catheter did not affect the migration of human fibroblasts. (3) The degradation of the new domestic polyglycolic acid neural catheter was similar to that of the imported neural catheter. Hematoxylin-eosin staining showed that the new domestic polyglycolic acid neural catheter had no significant effect on the major organs of rats. Masson staining showed that the tissues surrounding the neural catheter in both groups of rats were normal, with no inflammatory cell infiltration observed. (4) The results indicate that the new domestic polyglycolic acid neural catheter has good degradability and no biotoxicity. 
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    Properties of boron nitride nanosheet-reinforced resin-matrix ceramics
    Zhang Mindi, Ma Teng, Su Qilong, Diao Kaixuan, Ren Guanghui,
    2026, 30 (26):  6899-6906.  doi: 10.12307/2026.362
    Abstract ( 55 )   PDF (2908KB) ( 18 )   Save
    BACKGROUND: Boron nitride nanosheets have demonstrated remarkable advantages in enhancing the properties of dental materials. However, the current research on boron nitride nanosheets-reinforced resin-matrix ceramic materials is still in the preliminary exploration stage.
    OBJECTIVE: To investigate the effect of boron nitride nanosheet addition on the properties of resin-matrix ceramics.
    METHODS: 60% bisphenol A glycidyl methacrylate and 40% triethylene glycol dimethacrylate were used as the resin matrix, and barium glass powder was used as the inorganic filler. Resin-matrix ceramics were prepared by mixing 83% (mass fraction) of the resin matrix with 17% (mass fraction) of the barium glass powder. Meanwhile, boron nitride nanosheets were added to replace the barium glass powder at mass fractions of 0.3%, 0.5%, 0.7%, and 0.9% to prepare 0.3%, 0.5%, 0.7%, and 0.9% (mass fractions) of boron nitride nanosheet/resin-matrix ceramics, respectively. Resin-matrix ceramics were co-cultured with extracts of 0.3%, 0.5%, 0.7%, and 0.9% boron nitride nanosheets/resin-matrix ceramics, respectively, and mouse fibroblast L929 cells (or human umbilical vein endothelial cells). The CCK-8 assay was used to assess cell viability, and L929 cell viability was assessed using live/dead staining. The wettability, mechanical properties, and wear resistance of the resin-matrix ceramics and extracts of 0.3%, 0.5%, 0.7%, and 0.9% boron nitride nanosheets/resin-matrix ceramics were evaluated.
    RESULTS AND CONCLUSION: (1) After co-culture with the resin-matrix ceramics and extracts of 0.3%, 0.5%, 0.7%, and 0.9% boron nitride nanosheets/resin-matrix ceramics, the survival rates of both L929 and human umbilical vein endothelial cells exceeded 85%, with no significant cytotoxicity. Live/dead staining revealed that the resin-matrix ceramics and extracts of 0.3%, 0.5%, 0.7%, and 0.9% boron nitride nanosheets/resin-matrix ceramics did not affect L929 cell viability. (2) With increasing boron nitride nanosheet mass fraction, the water contact angle of the resin-matrix ceramic increased, while the flexural strength and microhardness first increased and then decreased. The 0.5% boron nitride nanosheet/resin-matrix ceramic exhibited the highest flexural strength and microhardness. After 60 000 cycles, the wear depth and wear volume of the resin-matrix ceramic gradually increased with increasing boron nitride nanosheet mass fraction. After 120 000 cycles, the wear depth and wear volume of the resin-matrix ceramic first decreased and then increased with increasing boron nitride nanosheet mass fraction. These results indicate that the appropriate addition of boron nitride nanosheets can significantly improve the overall properties of resin-matrix ceramics.

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    Frontiers and hot topics of nanobiomedicine in delaying the progression of osteoarthritis
    Wu Ningyuan, Wei Zhiyi, Feng Hao, Gao Ming
    2026, 30 (26):  6907-6915.  doi: 10.12307/2026.389
    Abstract ( 105 )   PDF (1560KB) ( 20 )   Save
    BACKGROUND: The application of nanobiomedicine can effectively alleviate oxidative stress in osteoarthritis, reduce inflammatory responses of osteoarthritis, and promote joint surface repair, thus delaying the occurrence and development of osteoarthritis. 
    OBJECTIVE: To review the research status, future development, and challenges of nanobiomedicine in delaying the progression of osteoarthritis. 
    METHODS: The first author searched for articles indexed in the CNKI, PubMed, Scopus, and Web of Science databases. The literature search time limit was from the establishment of each database to April 2025. The Chinese and the English search terms were "nanobiomedicine, nanocomposited hydrogel, engineered organisms, osteoarthritis." Finally, 90 articles that met the criteria were selected for review.
    RESULTS AND CONCLUSION: Nanobiomedical research is constantly evolving, with nanobiomaterials becoming a mainstream research direction in the treatment of osteoarthritis. Nanobiomedical materials possess anti-inflammatory and antioxidant properties, cartilage repair, precise drug delivery, cell differentiation promotion, and targeted therapy, offering a new avenue for the treatment of osteoarthritis that transcends the limitations of traditional therapies (such as short-term drug effects, significant adverse reactions, and surgical trauma). Nanobiomedical design concepts, based on multi-responsive mechanisms such as pH, enzymes, and temperature, integrate intelligent responses with enhanced functionality, enabling precise and controlled drug release from nano-drug delivery systems.

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    Selenium effect on human bone health and its application in bone materials
    Ye Gaoqi, Gong Yukang, Chen Dejin, Gao Wenshan
    2026, 30 (26):  6916-6922.  doi: 10.12307/2026.827
    Abstract ( 33 )   PDF (1570KB) ( 15 )   Save
    BACKGROUND: In recent years, selenium modified bone repair materials have shown great potential in the treatment of bone diseases and regenerative repair.
    OBJECTIVE: To summarize the construction strategies of different types of selenium modified bone repair materials, as well as the effects, mechanisms, and repair promoting effects of regulating the immune microenvironment of bone regeneration.
    METHODS: CNKI, WanFang, PubMed, and ScienceDirect databases were searched for literature published from database inception to 2025, using the Chinese search terms “selenium, bone defect, osteoporosis, Kashin Beck disease, osteosarcoma” and English search terms “selenium, bone defect, osteoporosis, osteoarthritis, Kashin Beck disease, osteosarcoma.” By reading literature for initial screening, duplicate and irrelevant articles were excluded, and ultimately 64 articles were included for review.
    RESULTS AND CONCLUSION: Selenium has anti-inflammatory, antioxidant, and bone promoting properties, which can effectively improve the immune microenvironment for bone regeneration. Selenium has high toxicity, but introducing selenium into bone materials can effectively diminish the toxicity of selenium. Selenium is often incorporated into bone repair materials using methods like mesoporous particles, nanoparticles, hydrogen bonds, and covalent bonds (diselenoses). In composite materials, selenium uses its antioxidant and anti-inflammatory properties to regulate the immune environment and encourage osteogenic gene expression. This creates a favorable environment for bone defect repair and regeneration. Selenium also shows promise for treating Kashin-Beck disease by preventing cell death, promoting chondrocyte renewal, and regulating the cellular environment. Furthermore, by preventing cell death, acting as an antioxidant, slowing aging, and boosting cartilage synthesis, it can improve the environment around chondrocytes, offering a new approach to treating osteoarthritis. However, much of the research is currently still in early stages, and significant challenges must be addressed before it can be used clinically.

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    Three-dimensional bioprinting and tendon repair: application advances and future directions 
    Liu Xuemiao, Zhang Yuchang, Zhang Weiguo, Tian Kang, Wang Xing
    2026, 30 (26):  6923-6929.  doi: 10.12307/2026.828
    Abstract ( 55 )   PDF (1373KB) ( 27 )   Save
    BACKGROUND: Currently, three-dimensional (3D) bioprinting technology, with its controllable multi-scale structure and functional integration design capabilities, has become a cutting-edge solution for tendon tissue engineering. 
    OBJECTIVE: To systematically summarize the latest research progress of 3D bioprinting technology in tendon repair. 
    METHODS: Using the keywords “3D printing, bioink, myotendinous junction, tendon repair, tendon-bone junction, bionic scaffold,” literature searches were conducted in the PubMed and Web of Science databases, as well as in the China National Knowledge Infrastructure (CNKI) with the same keywords. Articles with weak relevance to the topic were excluded, and 109 articles were ultimately included for review.
    RESULTS AND CONCLUSION: 3D bioprinting technology, through multi-material integration and controllable biomimetic structure design, effectively reproduces the multi-level structure of tendons. Mainstream technologies (such as melt electrospinning and extrusion printing) play differentiated advantages in fiber arrangement, interface simulation, and dynamic regulation, constructing mechanical transition layers at the muscle-tendon interface and four-zone gradient structures at the tendon-bone interface. Functional innovations in bioinks (such as immunomodulatory materials and cross-species oxygen supply scaffolds) and multi-technology synergy (directional fiber deposition + photo-curing enhancement) enhance the biological activity and mechanical-biological coupling ability of the scaffolds. Throughout the entire healing cycle (support in the inflammatory phase, guidance in the proliferative phase, and regulation in the remodeling phase), it achieves precise intervention from the molecular to the macroscopic level, optimizing collagen arrangement and repair mechanical properties. Differentiated repair strategies for the muscle-tendon interface, tendon body, and tendon-bone interface (such as multi-material gradients, directional fibers, and gradient scaffolds) have made progress. Despite challenges such as the resolution-efficiency contradiction and insufficient material matching, 3D printing technology still provides new strategies from structural biomimicry to functional regeneration for tendon repair. The integration of smart materials (such as photothermal/piezoelectric) and multi-modal technologies (such as 4D printing and organoids) in the future is expected to promote dynamic functional regeneration and provide technical references for interface repair.
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    Development and application of natural oral hydrogels in drug delivery systems
    Yang Qi, Xiang Xi, Wang Han, Zou Zhen, Zhang Lunci, Mireadeli·Abulimiti, Liao Yue, Li Xinzhi
    2026, 30 (26):  6930-6936.  doi: 10.12307/2026.737
    Abstract ( 49 )   PDF (1352KB) ( 14 )   Save
    BACKGROUND: Oral drug delivery has consistently been the most preferred route of administration due to its high patient compliance, significantly enhancing the overall treatment experience compared to injectables. However, the gastrointestinal environment severely limits drug bioavailability. As the demand for biocompatibility and biodegradability in the medical field continues to grow, natural hydrogels have emerged as ideal drug delivery carriers, attracting widespread attention.
    OBJECTIVE: To explore the development and application of oral hydrogels made from various natural materials, from material selection to synthesis methods.
    METHODS: A comprehensive literature search was conducted in the PubMed and Web of Science databases using the English search terms “oral hydrogels, physical crosslinking, chemical crosslinking, natural material, therapy, drug delivery, application of disease research” to identify the most recent relevant articles published from 2009 to 2024. A total of 83 articles were selected for review.
    RESULTS AND CONCLUSION: Hydrogels, as a promising new drug delivery system, exhibit significant advantages in achieving precise drug delivery and controlled release. Oral natural hydrogels stand out in the field of drug delivery due to their excellent biocompatibility, good biodegradability, and extremely low potential toxicity. They not only enable precise drug delivery but also effectively avoid irritation caused by direct contact between the drug and the gastrointestinal tract, providing a safer and more effective route for drug delivery. With the tireless exploration of researchers, new intelligent hydrogel delivery systems based on natural materials are constantly emerging, such as pectin-based pH-responsive hydrogels and hyaluronic acid-based reactive oxygen species-responsive hydrogels. These new materials have opened up new avenues for intelligent and precise drug delivery. However, the application of natural hydrogels has also exposed some unresolved issues. On the one hand, natural materials generally suffer from insufficient mechanical properties and tensile strength, making them difficult to meet complex drug delivery requirements. On the other hand, despite their natural origin, natural materials can still trigger immune responses in the human body.
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    Main preparation methods of new fluorescent nanomaterial carbon quantum dots and their applications in tumor diagnosis and treatment
    Guo Zhiyou, Hu Rui, Zhu Jinling
    2026, 30 (26):  6937-6945.  doi: 10.12307/2026.759
    Abstract ( 76 )   PDF (2677KB) ( 176 )   Save
    BACKGROUND: Carbon quantum dots are a novel fluorescent nanomaterial that, thanks to their excellent optical properties, good biocompatibility, and low toxicity, show significant potential in the field of tumor diagnosis and treatment.
    OBJECTIVE: To systematically review the methods used to prepare carbon quantum dots and their applications in tumor diagnosis and treatment.
    METHODS: Relevant literature was retrieved from the China National Knowledge Infrastructure (CNKI) and PubMed databases using computer searches. Chinese search terms were “tumor therapy, carbon quantum dots, arc discharge, electrochemical discharge, drug delivery, fluorescence imaging.” English search terms were “CQD tumor therapy, carbon quantum dot preparation, carbon quantum dots, tumor diagnosis and treatment.” According to the inclusion and exclusion criteria, 102 articles were finally included in the review.
    RESULTS AND CONCLUSION: Common preparation methods for carbon quantum dots are top-down method and bottom-up method. In terms of preparation, the top-down method (arc discharge, electrochemical, laser ablation) uses graphite and other carbon materials as precursors, which is simple to operate but produces many by-products and has low quantum yield; after purification, the yield can be improved. The bottom-up method (hydrothermal, microwave, and template) utilizes biomass or small-molecule carbon sources, offering environmental friendliness and excellent water solubility of the products. In tumor diagnosis and therapy, carbon quantum dots exert their effects through multiple synergistic mechanisms. Fluorescence imaging enables early tumor diagnosis and real-time monitoring using carbon quantum dots as fluorescent probes for labeling tumor cells. In photothermal therapy, the photothermal conversion efficiency of carbon quantum dots is used to convert light energy into heat energy to kill tumor cells. In photodynamic therapy, carbon quantum dots produce reactive oxygen species to destroy tumor cell biomacromolecules. As drug carriers, carbon quantum dots can deliver anti-tumor drugs to the tumor site in a targeted manner, reducing adverse reactions. In immunotherapy, “cold tumors” are converted into “hot tumors” by triggering immunogenic death, reversing the immunosuppressive microenvironment, and activating the interferon-stimulating factor pathway. In multimodal treatment, carbon quantum dots achieve a high tumor inhibition rate by integrating chemotherapy, phototherapy, and immunotherapy.
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    A network meta-analysis of therapeutic effects of different bone repair materials on apical bone defects
    Zhang Kaijing, Li Chunnian, Li Yizhuo, Xu Shifang, Liu Xinyue
    2026, 30 (26):  6946-6951.  doi: 10.12307/2026.826
    Abstract ( 36 )   PDF (2169KB) ( 14 )   Save
    OBJECTIVE: To promote the regeneration of apical bone defects, autologous bone, xenograft bone, synthetic bone, and bioactive materials are commonly used clinically. However, a systematic comparison of the efficacy of each repair material is lacking. Therefore, this study used a network meta-analysis to comprehensively compare and evaluate the differences in efficacy of different bone repair materials in treating apical bone defects.
    METHODS: Randomized controlled trials on the treatment of apical bone defects caused by chronic periapical periodontitis or apical cysts using bone repair materials were searched in databases including CNKI, WanFang Data, VIP, SinoMed, PubMed, Embase, Web of Science, and Cochrane Library. The search period was from database inception to July 20, 2025. According to the Cochrane Handbook of Evaluation, RevMan 5.4 software was used to assess the risk of bias in the included literature. Stata 17MP was used for statistical analysis.
    RESULTS: A total of 21 studies involving 1 286 patients were included, evaluating 10 interventions: hydroxyapatite, deproteinized bovine bone mineralz, collagen membrane, hydroxyapatite + collagen membrane, deproteinized bovine bone mineralz + collagen membrane, concentrated growth factor, platelet-rich fibrin, gelatin sponge, blank control (natural healing of blood clot), and platelet-rich plasma. The network meta-analysis revealed the following rankings: (1) Treatment efficacy (from best to worst): The top three interventions were hydroxyapatite + collagen membrane > deproteinized bovine bone mineralz + collagen membrane > concentrated growth factor. (2) Incidence of adverse reactions (from highest to lowest): Gelatin sponge > blank control > hydroxyapatite > hydroxyapatite + collagen membrane. 
    CONCLUSION: For the treatment of apical bone defects, the combination of hydroxyapatite and a collagen membrane demonstrated the most significant therapeutic efficacy and the lowest incidence of postoperative adverse reactions. Due to limitations in the number and quality of the included studies, further more clinical trials are needed to validate these findings.

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    Research status and trends of nanotechnology in improving photodynamic therapy for hypoxic tumors
    Dilida·Bahetikelede, Zhou Xin, Wang Xinyi, Zeng Zhihan, Wang Liqiong, Hu Danrong
    2026, 30 (26):  6952-6960.  doi: 10.12307/2026.384
    Abstract ( 40 )   PDF (2836KB) ( 6 )   Save
    BACKGROUND: Photodynamic therapy, a novel tumor treatment, is limited by the hypoxic tumor microenvironment. Nanotechnology-based oxygen regulation strategies offer a novel approach to overcoming this bottleneck.
    OBJECTIVE: To systematically analyze the current status of nanotechnology research in improving photodynamic therapy for hypoxic solid tumors using bibliometric methods, identify hot topics in the field, and predict future development directions.
    METHODS: Using the Web of Science Core Collection database as the data source, we retrieved relevant papers and reviews on the use of nanotechnology in regulating tumor hypoxia and enhancing the efficacy of photodynamic therapy from 2016 to 2025. Visualizations of the Web of Science Core Collection database categories, publication trends, countries, institutions, authors, co-citations, and keywords were analyzed using Excel, CiteSpace, VOSviewer, and Bibliometrix.
    RESULTS AND CONCLUSION: A total of 1 879 articles were included, with “nanoscience & nanotechnology” being the core category. The number of articles published in the field of nanotechnology-based photodynamic therapy for hypoxic tumors continued to grow from 2016 to 2022, with a brief decline in 2023 before recovering. China is the leading country in the field of nanotechnology-based photodynamic therapy for hypoxic tumors. The Chinese Academy of Sciences has the highest number of publications, while Liu Zhuang from Soochow University has the highest number of publications. The 2016 publication by ZHOU ZJ et al. in Chemical Society Reviews has the highest total citation count. This research area focuses on cancer treatment and microenvironment-responsive phototherapy strategies using nanomaterials. The keywords “photodynamic therapy” and “nanoparticles” appear most frequently. Bibliometric analysis indicates that nanotechnology has advantages in improving the efficacy of photodynamic therapy for hypoxic tumors. Related research demonstrates good efficacy and safety, and future research is likely to focus on combination strategies with immunotherapy.
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    Hand tendon suturing: optimization of traditional suture techniques and application of novel repair materials
    Zhou Ningyu, Zheng Yuxiang, Zhang Xiaoyang, Weng Yuxun, Yang Yinrui, Zhou Qijian, Zheng Jinchen, Liu Hongying, Sun Chenchen, Liu Zheng
    2026, 30 (26):  6961-6968.  doi: 10.12307/2026.399
    Abstract ( 32 )   PDF (40872KB) ( 12 )   Save
    BACKGROUND: The tendon suturing technique for the hand has been continuously innovated with the development of biomechanics, minimally invasive techniques, and regenerative medicine. Over the past two decades, research has focused on optimizing traditional suturing techniques and the application of new repair materials, improving the effectiveness of tendon repair and the level of functional recovery in the hand.
    OBJECTIVE: To assess the global research status and development trends of hand tendon repair techniques over the past two decades through bibliometric analysis, identify research hotspots and their evolution. 
    METHODS: Relevant literature was selected from the Web of Science database from 2005 to 2024, and bibliometric methods were employed for analysis. Data were organized using Microsoft Excel and analyzed for publication trends using the R language Bibliometrix package. VOSviewer was used to visualize keyword co-occurrence and collaboration networks, while CiteSpace was utilized to identify research hotspots and their temporal evolution. 
    RESULTS AND CONCLUSION: Over the past two decades, research in the field of tendon suturing has shown a fluctuating growth trend. The United States, China, and Europe are the main contributors to the research, with the United States occupying a central position in the global research network. Research on flexor tendon repair mainly focuses on biomechanics and the development of new suturing materials, while extensor tendon research emphasizes postoperative functional recovery and complex injury repair. In recent years, biomaterials and regenerative medicine have gradually become research hotspots, driving the application of precision medicine in tendon repair. In the future, interdisciplinary collaboration and the integration of advanced materials will further optimize hand tendon repair techniques.

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