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Bioinspired Tactile Sensation Based on Synergistic Microcrack-Bristle Structure Design toward High Mechanical Sensitivity and Direction-Resolving Capability

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Research 2024年第1期2023卷 611-624页

作者： Yiqun Zhang Qi Liu Wenjuan Ren Yangyang Song Hua Luo Yangyang Han Liang He Xiaodong Wu Zhuqing Wang School of Mechanical Engineering Sichuan UniversityChengdu 610065China med+X Center for Manufacturing West China HospitalSichuan UniversityChengdu 610041China State Key Laboratory of Polymer Materials Engineering Polymer Research Institute of Sichuan UniversityChengdu 610065China

Natural tactile sensation is complex,which involves not only contact force intensity detection but also the perception of the force direction,the surface texture,and other mechanical parameters.Nevertheless,the vast majority of the developed tactile sensors can only detect the normal force,but usually cannot resolve shear force or even distinguish the directions of the force.Here,we present a new paradigm of bioinspired tactile sensors for resolving both the intensity and the directions of mechanical stimulations via synergistic microcrack-bristle structure design and cross-shaped configuration engineering.The microcrack sensing structure gives high mechanical sensitivity to the tactile sensors,and the synergistic bristle structure further amplifies the sensitivity of the sensors.The cross-shaped configuration engineering of the synergistic microcrack-bristle structure further endows the tactile sensors with good capability to detect and distinguish the directions of the applied mechanical forces.The as-fabricated tactile sensors exhibit a high sensitivity(25.76 N^(−1)),low detection limit(5.4 mN),desirable stability(over 2,500 cycles),and good capability to resolve both mechanical intensity and directional features.As promising application scenarios,surface texture recognition and biomimetic path explorations are successfully demonstrated with these tactile sensors.This newly proposed tactile sensation strategy and technology have great potential applications in ingenious tactile sensation and construction of various robotic and bionic prostheses with high operational dexterity.

关键词： crack sensation directions

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A pH/ROS dual-responsive system for effective chemoimmunotherapy against melanoma via remodeling tumor immune microenvironment

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2263-2280页

作者： Leilei Wang Shanshan He Rong Liu Yuan Xue Yuan Quan Rongying Shi Xueying Yang Qing Lin Xun Sun Zhirong Zhang Ling Zhang Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry West China School of PharmacySichuan UniversityChengdu 610041China med-X Center for Materials College of Polymer Science and EngineeringSichuan UniversityChengdu 610065China

Chemotherapeutics can induce immunogenic cell death(ICD)in tumor cells,offering new possibilities for cancer therapy.However,the efficiency of the immune response generated is insufficient due to the inhibitory nature of the tumor microenvironment(TME).Here,we developed a pH/reactive oxygen species(ROS)dual-response system to enhance chemoimmunotherapy for melanoma.The system productively accumulated in tumors by specific binding of phenylboronic acid(PBA)to sialic acids(SA).The nanoparticles(NPs)rapidly swelled and released quercetin(QUE)and doxorubicin(DOX)upon the stimulation of tumor microenvironment(TME).The in vitro and in vivo results consistently demonstrated that the NPs improved anti-tumor efficacy and prolonged survival of mice,significantly enhancing the effects of the combination.Our study revealed DOX was an ICD inducer,stimulating immune responses and promoting maturation of dendritic cells(DCs).Additionally,QUE served as a TME regulator by inhibiting the cyclooxygenase-2(COX2)-prostaglandin E2(PGE2)axis,which influenced various immune cells,including increasing cytotoxic T cells(CLTs)infiltration,promoting M1 macrophage polarization,and reducing regulatory T cells(Tregs)infiltration.The combination synergistically facilitated chemoimmunotherapy efficacy by remodeling the immunosuppressive microenvironment.This work presents a promising strategy to increase anti-tumor efficiency of chemotherapeutic agents.

关键词： Quercetin Nanoparticle Responsiveness Chemoimmunotherapy Tumor immune microenvironment

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Anti-osteosarcoma trimodal synergistic therapy using NiFe-LDH and MXene nanocomposite for enhanced biocompatibility and efficacy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1329-1344页

作者： Yani Xu Lan Yang Min Li Haozhou Shu Na Jia Yunzhen Gao Rongying Shi Xiaojia Yang Zhirong Zhang Ling Zhang Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry West China School of PharmacySichuan UniversityChengdu 610041China med-X Center for Materials College of Polymer Science and EngineeringSichuan UniversityChengdu 610065China

Osteosarcoma is usually resistant to immunotherapy and,thus primarily relies on surgical resection and high-dosage chemotherapy.Unfortunately,less invasive or toxic therapies such as photothermal therapy(PTT)and chemodynamic therapy(CDT)generally failed to show satisfactory outcomes.Adequate multimodal therapies with proper safety profiles may provide better solutions for osteosarcoma.Herein,a simple nanocomposite that synergistically combines CDT,PTT,and chemotherapy for osteosarcoma treatment was fabricated.In this composite,small 2D Ni Fe-LDH flakes were processed into 3D hollow nanospheres via template methods to encapsulate 5-Fluorouracil(5-FU)with high loading capacity.The nanospheres were then adsorbed onto larger 2D Ti3C2MXene monolayers and finally shielded by bovine serum albumin(BSA)to form 5-FU@Ni Fe-LDH/Ti3C2/BSA nanoplatforms(5NiTiB).Both in vitro and in vivo data demonstrated that the 5-FU induced chemotherapy,Ni Fe-LDH driven chemodynamic effects,and MXene-based photothermal killing collectively exhibited a synergistic“all-in-one”anti-tumor effect.5NiTiB improved tumor suppression rate from<5%by 5-FU alone to~80.1%.This nanotherapeutic platform achieved higher therapeutic efficacy with a lower agent dose,thereby minimizing side effects.Moreover,the composite is simple to produce,enabling the fine-tuning of dosages to suit different requirements.Thus,the platform is versatile and efficient,with potential for further development.

关键词： Osteosarcoma NiFe-LDH MXene Chemodynamic therapy Photothermal therapy Chemotherapy 5-Fluorouracil Nanocomposite

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Minimalistic approach to left atrial appendage occlusion guided by cardiac computed tomography angiography

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Journal of Geriatric Cardiology 2024年第4期21卷 431-442页

作者： Xian-Sai MENG Qing-Song WANG Xin-Yan WANG Xu LU Yang MU Jing WANG Ting-Ting SONG Yun-Dai CHEN Tao CHEN Jun GUO Graduate School of Chinese PLA medical College BeijingChina Senior Department of Cardiology the Sixth Med-ical CenterChinese PLA General HospitalBeijingChina

OBJECTIVE To assess the feasibility and safety of the minimalistic approach to left atrial appendage occlusion(LAAO) guided by cardiac computed tomography angiography(CCTA).METHODS Ninety consecutive patients who underwent LAAO, with or without CCTA-guided, were matched(1:2). Each step of the LAAO procedure in the computed tomography(CT) guidance group(CT group) was directed by preprocedural CT planning. In the control group, LAAO was performed using the standard method. All patients were followed up for 12 months, and device surveillance was conducted using CCTA.RESULTS A total of 90 patients were included in the analysis, with 30 patients in the CT group and 60 matched patients in the control group. All patients were successfully implanted with Watchman devices. The mean ages for the CT group and the control group were 70.0 ± 9.4 years and 68.4 ± 11.9 years(P = 0.52), respectively. The procedure duration(45.6 ± 10.7 min vs. 58.8 ± 13.0 min,P < 0.001) and hospital stay(7.5 ± 2.4 day vs. 9.6 ± 2.8 day, P = 0.001) in the CT group was significantly shorter compared to the control group. However, the total radiation dose was higher in the CT group compared to the control group(904.9 ± 348.0 m Gy vs.711.9 ± 211.2 m Gy, P = 0.002). There were no significant differences in periprocedural pericardial effusion(3.3% vs. 6.3%, P = 0.8) between the two groups. The rate of postprocedural adverse events(13.3% vs. 18.3%, P = 0.55) were comparable between both groups at 12 months follow-up.CONCLUSIONS CCTA is capable of detailed LAAO procedure planning. Minimalistic LAAO with preprocedural CCTA planning was feasible and safe, with shortened procedure time and acceptable increased radiation and contras consumption. For patients with contraindications to general anesthesia and/or transesophageal echocardiography, this promising method may be an alternative to conventional LAAO.

关键词： anesthesia matched approach

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Endorepellin downregulation promotes angiogenesis after experimental traumatic brain injury

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Neural Regeneration Research 2024年第5期19卷 1092-1097页

作者： Qian Zhang Yao Jing Qiuyuan Gong Lin Cai Ren Wang Dianxu Yang Liping Wang Meijie Qu Hao Chen Yaohui Tang Hengli Tian Jun Ding Zhiming Xu Department of Gerontology Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Neurosurgery Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Neurology Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina School of Biomedical Engineering and med-X Research Institute Shanghai Jiao Tong UniversityShanghaiChina Department of Neurology Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina

Endorepellin plays a key role in the regulation of angiogenesis,but its effects on angiogenesis after traumatic brain injury are unclear.This study explored the effects of endorepellin on angiogenesis and neurobehavioral outcomes after traumatic brain injury in mice.Mice were randomly divided into four groups:sham,controlled cortical impact only,adeno-associated virus(AAV)-green fluorescent protein,and AAV-shEndorepellin-green fluorescent protein groups.In the controlled cortical impact model,the transduction of AAV-shEndorepellin-green fluorescent protein downregulated endorepellin while increasing the number of CD31+/Ki-67+proliferating endothelial cells and the functional microvessel density in mouse brain.These changes resulted in improved neurological function compared with controlled cortical impact mice.Western blotting revealed increased expression of vascular endothelial growth factor and angiopoietin-1 in mice treated with AAV-shEndorepellin-green fluorescent protein.Synchrotron radiation angiography showed that endorepellin downregulation promoted angiogenesis and increased cortical neovascularization,which may further improve neurobehavioral outcomes.Furthermore,an in vitro study showed that downregulation of endorepellin increased tube formation by human umbilical vein endothelial cells compared with a control.Mechanistic analysis found that endorepellin downregulation may mediate angiogenesis by activating vascular endothelial growth factor-and angiopoietin-1-related signaling pathways.

关键词： angiogenesis controlled cortical impact endorepellin neurological function traumatic brain injury

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Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity

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Acta Pharmaceutica Sinica B 2024年第1期14卷 350-364页

作者： Yongshun Zhang Lan Yang Yangsen Ou Rui Hu Guangsheng Du Shuang Luo Fuhua Wu Hairui Wang Zhiqiang Xie Yu Zhang Chunting He Cheng Ma Tao Gong Ling Zhang Zhirong Zhang Xun Sun Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China med-X Center for Materials College of Polymer Science and EngineeringSichuan UniversityChengdu 610065China

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10(PTEN)gene in cancer cells may be associated with immunosuppressive tumor microenvironment(TME)and poor response to immune checkpoint blockade(ICB)therapy.Therefore,efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy.Here,we screened an adeno-associated virus(AAV)capsid for efficient PTEN gene delivery into B16F10 tumor cells.We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death(ICD)and increasing immune cell infiltration.Moreover,we developed an anti-PD-1 loaded phospholipid-based phase separation gel(PPSG),which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo.In order to effectively inhibit the recurrence of melanoma,we further applied a triple therapy based on AAV6-PTEN,PPSG^(@anti-PD-1)and CpG,and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory,which completely rejected tumor recurrence.We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

关键词： Triple therapy Adeno-associated virus PTEN PPSG@anti-PD-1 CpG Immunogenic cell death Antitumor immune response Immune memory

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Pien Tze Huang Inhibits Migration and Invasion of Hepatocellular Carcinoma Cells by Repressing PDGFRB/YAP/CCN2 Axis Activity

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Chinese Journal of Integrative medicine 2024年第2期30卷 115-124页

作者： LUO Zhi-yi TIAN Qi CHENG Niang-mei LIU Wen-han YANG Ye CHEN Wei ZHANG Xiang-zhi ZHENG Xiao-yuan CHEN Ming-sheng ZHUANG Qiu-yu ZHAO Bi-xing LIU Cong-sheng LIU Xiao-long LI Qin WANG Ying-chao The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou(350025)China Fujian Pien Tze Huang Enterprise Key Laboratory of Natural medicine Research and Development Zhangzhou Pien Tze Huang Pharmaceutical Co.Ltd.ZhangzhouFujian Province(363099)China College of Biological Science and Engineering and Mengchao med-X Center Fuzhou UniversityFuzhou(350116)China Department of Internal medicine Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou(350025)China

Objective:To investigate the effects of Pien Tze Huang(PZH) on the migration and invasion of HCC cells and underlying molecular mechanism.Methods:Cell counting kit-8(CCK-8) was applied to evaluate the cell viabilities of SMMC-7721,SK-Hep-1,C3A and HL-7702(6 × 10^(3)cells/well) co-incubated with different concentrations of PZH(0,0.2,0.4,0.6,0.8 mg/mL) for 24 h.Transwell,wound healing assay,CCK-8and Annexin V-FITC/PI staining were conducted to investigate the effects of PZH on the migration,invasion,proliferation and apoptosis of SK-Hep-1 and SMMC-7721 cells(650 μg/mL for SK-Hep-1 cells and 330 μg/mL for SMMC-7721 cells),respectively.In vivo,lung metastasis mouse model constructed by tail vein injection of HCC cells was used for evaluating the anti-metastasis function of PZH.SK-Hep-1 cells(10^(6)cells/200 μL per mice) were injected into B-NDG mice via tail vein.Totally 8 mice were randomly divided into PZH and control groups,4 mice in each group.After 2-d inoculation,mice in the PZH group were administered with PZH(250 mg/kg,daily) and mice in the control group received only vehicle(PBS) from the 2nd day after xenograft to day 17.Transcriptome analysis based on RNA-seq was subsequently used for deciphering anti-tumor mechanism of PZH.Quantitative real-time polymerase chain reaction(qRT-PCR) and Western blot were applied to verify RNA-seq results.Luciferase reporter assay was performed to examine the transcriptional activity of yes-associated protein(YAP).Results:PZH treatment significantly inhibited the migration,invasion,proliferation and promoted the apoptosis of HCC cells in vitro and in vivo(P<0.01).Transcriptome analysis indicated that Hippo signaling pathway was associated with anti-metastasis function of PZH.Mechanical study showed PZH significantly inhibited the expressions of platelet derived growth factor receptor beta(PDGFRB),YAP,connective tissue growth factor(CCN2),N-cadherin,vimentin and matrix metallopeptidase 2(MMP2,P<0.01).Meanwhile,the phosphorylation of YAP was also enhanced by PZH treatment in v

关键词： PienTzeHuang hepatocellular carcinoma RNA-seq Hippo yes-associated protein

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Factors and Their Impact on Treatment Effect of Acupuncture in Different Outcomes:A Meta-Regression of Acupuncture Randomized Controlled Trials

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Chinese Journal of Integrative medicine 2024年第3期30卷 260-266页

作者： XIU Wen-cui GANG Wei-juan ZHOU Qi SHI Lan-jun HU Xiang-yu MING Tian-yu LUO Zhen ZHANG Yu-qing JING Xiang-hong Institute of Acupuncture and Moxibustion China Academy of Chinese Medical SciencesBeijing100700China china Center for Evidence-Based Traditional Chinese medicine China Academy of Chinese Medical SciencesBeijing100700China Department of Health Research Methods Evidenceand ImpactMcMaster UniversityHamiltonOntarioL8S 4L8Canada Center for Evidence-Based Integrative medicine-Clarity Collaboration Guang’anmen HospitalChina Academy of Chinese Medical SciencesBeijing100053China

Background:The effects of acupuncture have varied in different randomized controlled trials(RCTs),and there are many factors that influence treatment effect of acupuncture in different outcomes,with conflicting results.Objective:To identify factors and their impact on the treatment effect of acupuncture in different outcomes.Methods:Acupuncture RCTs were searched from 7 databases including medline(Pub med),Embase,Cochrane Central Register of Controlled Trials,china National Knowledge Infrastructure,Wanfang Database,VIP Database,and china Biology medicine disc between January 1st,2015 and December 31st,2019.Eligible studies must compare acupuncture to no acupuncture,sham acupuncture,or waiting lists,and report at least 1patient-important outcome.A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables,even those excluded from the multivariable model due to collinearities.We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences(SMDs),categorising them as small(0.4) effects.Results:The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables.High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude,the difference of adjusted SMDs 0.46,95% confidence interval(CI) 0.07 to 0.84;P=0.02].The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables.Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture(0.30,95% CI 0.06 to 0.53;P=0.01).The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables.Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects,compared to non-penetrating acupuncture and fixed regimen,respectively(0.40,95% CI 0 to 0.80;P=0.05;0.29,95% CI 0.06 to 0.53;P=0.01).

关键词： acupuncture randomized controlled trial patient-important outcome meta-regression

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Direct detection of C9orf72 hexanucleotide repeat expansions by nanopore biosensor

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Chinese Chemical Letters 2024年第5期35卷 351-354页

作者： Xinqiong Li Guocheng Rao Xi Peng Chan Yang Yanjing Zhang Yan Tian Xianghui Fu Jia Geng State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengdu 610041China Division of Endocrinology and Metabolism West China School of Medicine/West China HospitalSichuan UniversityChengdu 610041China Department of Endocrinology and Metabolism Affiliated Hospital of North Sichuan Medical CollegeNorth Sichuan Medical CollegeNanchong 637000China Division of Endocrinology and Metabolism National Clinical Research Center for GeriatricsState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengdu 610041China Department of Laboratory medicine State Key Laboratory of BiotherapyMed-X Center for ManufacturingWest China HospitalSichuan University and Collaborative Innovation CenterChengdu 610041China Tianfu Jincheng Laboratory City of Future MedicineChengdu 641400China

Diagnostic C9orf72 hexanucleotide repeat expansions(C9-HRE)is essential for the early and accurate diagnosis of amyotrophic lateral sclerosis(ALS)and will provide support for the prognosis and gene therapy of ALS.In the present study,by combining catalytic hairpin assembly(CHA)with Mycobacterium smegmatis porin A(MspA)nanopore,a new nanopore-based strategy for the detection of C9-HRE was reported.Less than 30 repeats of C9-HRE could be detected via this method,and the results have the potential to help distinguish between patients and healthy individuals.Moreover,the method demonstrated its great specificity for C9-HRE by identifying other repeat expansions.Given the high selectivity,this approach had been successfully used to detect C9-HRE in cell and blood samples with high accuracy.This detection strategy is user-friendly and has a strong anti-interference ability,thus providing a powerful tool for clinical diagnosis.

关键词： MspA nanopore C9orf72 HRE Detection Biosensor Catalytic hairpin assembly

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Immediate implantation of ultrafine fiber slow-release system based on cell electrospinning to induce osteogenesis of mesenchymal stem cells

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Regenerative Biomaterials 2024年第2期3卷 76-87页

作者： Tao Lu Long Yang Zhuoyang Li Yin Liu Shun'en Xu Chuan Ye Department of Orthopaedics The Affliated Hospital of Guizhou Medical UniversityGuiyang 550004China Department of Orthopaedics The First People's Hospital of GuiyangGuiyang 550004China Center for Tissue Engineering and Stem Cell Research Guizhou Medical UniversityGuiyang 550004China Department of Otolaryngology Head and Neck Surgery Xinqiao HospitalArmy Medical University(Third Military Medical University)Chongqing 400037China Department of Dental implant Stomatological Hospital of GuiyangGuiyang 550000China

This study presents the development and evaluation of a poly(3-hydroxybutyrate-co-4-hydroxybutyrate)(P34HB)ultrafine fiber slow-release system for in vivo osteogenic induction of human umbilical cord mesenchymal stem cells(HUCMSCs).Utilizing dual-nozzle and cell electrospinning techniques,the system encapsulates L-ascorbic acid-2-phosphate magnesium(AsP),βB-glycerophosphate sodium and dexamethasone(DEX)within the'fbers,ensuring sustained osteogenic differentiation.The scaffold's morphology,characterization,hydrophilicity,mechanical properties and cellular behavior were examined.Immediate subcutaneous implantation in rabbits was con-ducted to observe its ectopic osteogenic induction effect.Successfully fabricated P34HB ultrafine fiber slow-release sys-tem.Charact ization med.theuniform distribution of HUCMSCs and inducing components within the scaffold,with no chemical reactions affecting the active components.In vitro tests showcased a prolonged release of DEX and ASP,while biocompatibility assays highlighted the scaffold's suitability for cellular growth.Alizarin Red,type I collagen,and osteopontin(OPN)staining verifed the scaffold's potent osteogenic induction effect on HUCMsCs.Notably,immediate implantation into New Zealand White rabbits led to significant new bone formation within 8 weeks.These findings underscore the system's potential for immediate in vivo implantation without prior in vitro induction,marking a promising advancement in bone tissue engineering.

关键词： bone tissue engineering cell electrospinning in vivo induction immediate implantation biomaterials

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