1.Development of Electrospinning Setup for Vascular Tissue-Engineering Application with Thick-Hierarchical Fiber Alignment
Shen CHEN ; Chao XIE ; Xiaoxi LONG ; Xianwei WANG ; Xudong LI ; Peng LIU ; Jiabin LIU ; Zuyong WANG
Tissue Engineering and Regenerative Medicine 2025;22(2):195-210
BACKGROUND:
Tissue engineering holds promise for vascular repair and regeneration by mimicking the extracellular matrix of blood vessels. However, achieving a functional and thick vascular wall with aligned fiber architecture by electrospinning remains a significant challenge.
METHODS:
A novel electrospinning setup was developed that utilizes an auxiliary electrode and a spring. The impact of process parameters on fiber size and morphology was investigated. The structure and functions of the scaffolds were evaluated through material characterization and assessments of cellular biocompatibility.
RESULTS:
The new setup enabled controlled deposition of fibers in different designed orientations. The fabricated small-diameter vascular scaffolds consisted of an inner layer of longitudinally oriented fibers and an outer layer of circumferentially oriented fibers (L + C vascular scaffold). Key parameters, including rotational speed, the utilization of the auxiliary electrode, and top-to-collector distance (TCD) significantly influenced fiber orientation. Additionally, voltage, TCD, feed rate, needle size, auxiliary electrode and collector-auxiliary electrode distance affected fiber diameter and distribution. Mechanical advantages and improved surface wettability of L + C vascular scaffold were confirmed through tensile testing and water contact angle. Cellular experiments indicated that L + C vascular scaffold facilitated cell adhesion and proliferation, with human umbilical vein endothelial cells and smooth muscle cells attaching and elongating along the fiber direction of the inner and outer layer, respectively.
CONCLUSION
This study demonstrated the feasibility of fabricating fiber-aligned, thick-walled vascular scaffolds using a modified electrospinning setup. The findings provided insights into how the auxiliary electrode, specific collector influenced fiber deposition, potentially advancing biomimetic vascular scaffold engineering.
2.Development of Electrospinning Setup for Vascular Tissue-Engineering Application with Thick-Hierarchical Fiber Alignment
Shen CHEN ; Chao XIE ; Xiaoxi LONG ; Xianwei WANG ; Xudong LI ; Peng LIU ; Jiabin LIU ; Zuyong WANG
Tissue Engineering and Regenerative Medicine 2025;22(2):195-210
BACKGROUND:
Tissue engineering holds promise for vascular repair and regeneration by mimicking the extracellular matrix of blood vessels. However, achieving a functional and thick vascular wall with aligned fiber architecture by electrospinning remains a significant challenge.
METHODS:
A novel electrospinning setup was developed that utilizes an auxiliary electrode and a spring. The impact of process parameters on fiber size and morphology was investigated. The structure and functions of the scaffolds were evaluated through material characterization and assessments of cellular biocompatibility.
RESULTS:
The new setup enabled controlled deposition of fibers in different designed orientations. The fabricated small-diameter vascular scaffolds consisted of an inner layer of longitudinally oriented fibers and an outer layer of circumferentially oriented fibers (L + C vascular scaffold). Key parameters, including rotational speed, the utilization of the auxiliary electrode, and top-to-collector distance (TCD) significantly influenced fiber orientation. Additionally, voltage, TCD, feed rate, needle size, auxiliary electrode and collector-auxiliary electrode distance affected fiber diameter and distribution. Mechanical advantages and improved surface wettability of L + C vascular scaffold were confirmed through tensile testing and water contact angle. Cellular experiments indicated that L + C vascular scaffold facilitated cell adhesion and proliferation, with human umbilical vein endothelial cells and smooth muscle cells attaching and elongating along the fiber direction of the inner and outer layer, respectively.
CONCLUSION
This study demonstrated the feasibility of fabricating fiber-aligned, thick-walled vascular scaffolds using a modified electrospinning setup. The findings provided insights into how the auxiliary electrode, specific collector influenced fiber deposition, potentially advancing biomimetic vascular scaffold engineering.
3.Development of Electrospinning Setup for Vascular Tissue-Engineering Application with Thick-Hierarchical Fiber Alignment
Shen CHEN ; Chao XIE ; Xiaoxi LONG ; Xianwei WANG ; Xudong LI ; Peng LIU ; Jiabin LIU ; Zuyong WANG
Tissue Engineering and Regenerative Medicine 2025;22(2):195-210
BACKGROUND:
Tissue engineering holds promise for vascular repair and regeneration by mimicking the extracellular matrix of blood vessels. However, achieving a functional and thick vascular wall with aligned fiber architecture by electrospinning remains a significant challenge.
METHODS:
A novel electrospinning setup was developed that utilizes an auxiliary electrode and a spring. The impact of process parameters on fiber size and morphology was investigated. The structure and functions of the scaffolds were evaluated through material characterization and assessments of cellular biocompatibility.
RESULTS:
The new setup enabled controlled deposition of fibers in different designed orientations. The fabricated small-diameter vascular scaffolds consisted of an inner layer of longitudinally oriented fibers and an outer layer of circumferentially oriented fibers (L + C vascular scaffold). Key parameters, including rotational speed, the utilization of the auxiliary electrode, and top-to-collector distance (TCD) significantly influenced fiber orientation. Additionally, voltage, TCD, feed rate, needle size, auxiliary electrode and collector-auxiliary electrode distance affected fiber diameter and distribution. Mechanical advantages and improved surface wettability of L + C vascular scaffold were confirmed through tensile testing and water contact angle. Cellular experiments indicated that L + C vascular scaffold facilitated cell adhesion and proliferation, with human umbilical vein endothelial cells and smooth muscle cells attaching and elongating along the fiber direction of the inner and outer layer, respectively.
CONCLUSION
This study demonstrated the feasibility of fabricating fiber-aligned, thick-walled vascular scaffolds using a modified electrospinning setup. The findings provided insights into how the auxiliary electrode, specific collector influenced fiber deposition, potentially advancing biomimetic vascular scaffold engineering.
4.Vascularization characteristics of tissue-engineered oral mucosa equivalents
Lijuan SHI ; Jian WEI ; Xuan ZHANG ; Lingxiao HE ; Xiaoxi JIANG ; Minhai NIE ; Jiana CHEN ; Xuqian LIU
Chinese Journal of Tissue Engineering Research 2025;29(22):4748-4760
BACKGROUND:In previous studies,the equivalent structure of three-dimensional cell reconstruction of tissue engineering oral mucosa is similar to normal oral mucosa,including epithelial-like structure,lamina propria-like structure,and vascular lumen-like structure,and has initially achieved the establishment of vascular equivalent,but its vascularization characteristics are not very clear.OBJECTIVE:Vascular-like structures of vascularized oral mucosa equivalent were obtained by targeting vascular endothelial cells specific marker expression profiles correlated with laser capture microdissection system,and their vascularization ability was evaluated to reveal their vascularization characteristics.METHODS:Human gingival epithelial cells were cultured from human gingival epithelium and human gingival fibroblasts,human gingival mesenchymal stem cells were cultured from human gingival lamina propria.Human gingival mesenchymal stem cells were induced to differentiate into vascular endothelial-like cells after monoclonal expansion culture.Human gingival epithelial cells,human gingival fibroblasts,and vascular endothelial-like cells were loaded with acellular vascular matrix-0.25%human-like collagen type Ⅰ scaffold to construct the vascularized oral mucosa equivalent.The layered structure of oral mucosa equivalent(experimental group)and the acellular vascular matrix-0.25%human-like collagen type Ⅰ scaffold(control group)were implanted subcutaneously into the back of nude mice,respectively.14 days later,the incision surface of the two groups was coated with biogel.The biogel surface of the experimental group was inoculated with human gingival epithelial cells,while the control group was not inoculated with cells.The samples were collected after 14 days of feeding.The layered structure of oral mucosa equivalent was observed by morphology.The neovascular-like structures in oral mucosa equivalents were labeled by immunohistochemistry and immunofluorescence with a more comprehensive expression profile of vascular endothelial cells,and the vascularization characteristics were analyzed.A laser capture microdissection system was used to capture the neovascularization structures in the oral mucosa equivalents specifically labeled by immunohistochemistry and analyze their vascularization characteristics.RESULTS AND CONCLUSION:(1)The morphology showed that the cell level of oral mucosa equivalent was clear,and the structure was similar to that of normal oral mucosa,that is,there were epithelioid structures,lamina-like structures,and vascular cavelike structures,and there were scattered erythrocytes in the vascular cavelike structures.(2)The results of EdU Apollo tracer seed cells in the oral mucosa equivalent group showed that human gingival epithelial cells labeled with EdU Apollo 488 showed green fluorescence expression.DAPI labeled human gingival fibroblasts showed blue fluorescence expression and formed lamina-like structures in vivo.EdU Apollo 567 labeled vascular endothelial-like cells showed red fluorescence expression and formed a vascular-like structure in vivo.(3)Vascular endothelial cell specific marker expression profile immunofluorescence labeling of vascular structure showed that compared with normal oral mucosa,the expressions of CD31,CD51,CD54,CD105,Tie-2,VWF,vascular endothelial growth factor receptor 1,and vascular endothelial growth factor receptor 2 in oral mucosa equivalents were increased(P<0.000 1).There were no significant changes in CD34 expression(P>0.05).(4)Compared with the specifically labeled oral mucosal vascular structures,the expression levels of CD51,CD54,CD105,Tie-2,VWF,vascular endothelial growth factor receptor 1,and vascular endothelial growth factor receptor 2 of the oral mucosa equivalents targeted by the laser capture microdissection system were increased(P<0.000 1).There were no significant changes in expression of CD31 and CD34(P>0.05).(5)The results showed that the oral mucosa equivalent reconstructed by three-dimensional cell stratification could achieve good vascularization,and its vascularization characteristics were consistent with the immunological function and characteristics of neovascularization.Vascularization helps three-dimensional cell layer reconstruction of oral mucosa equivalent regeneration.
5.Relationship between triglyceride-glucose index and acute ischemic stroke with anterior circulation large vessel occlusion
Ruyue LIN ; Jianqiang FAN ; Lijun WANG ; Xiaoxi ZHANG ; Hongjian SHEN ; Pengfei XING ; Lei ZHANG ; Zifu LI ; Yongwei ZHANG ; Pengfei YANG ; Jianmin LIU ; Rui ZHAO
Academic Journal of Naval Medical University 2025;46(4):435-441
Objective To explore the relationship between triglyceride-glucose index(TyG)and acute ischemic stroke with large vessel occlusion(AIS-LVO)of anterior circulation.Methods A retrospective study was conducted on patients with anterior circulation AIS-LVO who underwent emergency endovascular thrombectomy at Neurovascular Center of The First Affiliated Hospital of Naval Medical University from Jan.2018 to Dec.2019.According to modified Rankin scale(mRS)score 90 d after operation,the patients were assigned to favorable outcome group(mRS score 0-2)or unfavorable outcome group(mRS score 3-6),and the TyG was compared.According to the median of TyG,the patients were assigned to low-TyG group(TyG<8.57)or high-TyG group(TyG ≥8.57),and the clinical data,laboratory indexes,and imaging characteristics were compared.Receiver operating characteristic curve was used to evaluate the predictive value of TyG for poor prognosis.Results A total of 135 patients were enrolled,with 72 in the favorable outcome group and 63 in the unfavorable outcome group.The TyG of the unfavorable outcome group was significantly higher than that of the favorable outcome group(8.82+0.63 vs 8.43+0.60,P<0.001).There were 67 patients in the low-TyG group and 68 in the high-TyG group.Compared with the low-TyG group,the proportion of patients with hyperlipidemia history(P=0.003),systolic blood pressure at admission(P=0.018),fasting blood glucose level(P<0.001),and triglyceride level(P<0.001)were significantly higher in the high-TyG group,the infarct core volume was significantly larger(P=0.025),the high density lipoprotein-cholesterol level was significantly lower(P=0.013),and the mRS score 90 d after operation was significantly higher(3[1,5]vs 1[0,5],P=0.049).The TyG had certain predictive value for poor prognosis in anterior circulation AIS-LVO patients(area under curve value=0.662,95%confidence interval 0.571-0.753).Conclusion TyG is elevated in anterior circulation AIS-LVO patients with poor prognosis,and may be a potential prognostic indicator for anterior circulation AIS-LVO patients.
6.Clinical characteristics of congenital atresia of the oval window
Jiayu PAN ; Meixin CHEN ; Yang WANG ; Xingyu HUANG ; Xiaoxi CHEN ; Zhaohui LIU ; Chunlin ZHANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(10):1252-1258
Objective:To investigate the clinical features of patients with congenital atresia of the oval window (CAOW).Methods:A retrospective analysis was conducted on 7 cases (8 ears) of surgically confirmed CAOW treated at our department from July 2018 to July 2024. Among the cases, 1 patient had bilateral CAOW, and 4 patients had unilateral CAOW combined with other types of ossicular chain malformations in the contralateral ear. We collected and analyzed the clinical data, audiological features, and temporal bone HRCT results of all patients.Results:The 7 patients were diagnosed at ages ranging from 8 to 19 years, with a mean age of (13.2±6.9) years. None of the patients exhibited significant auricular deformities. All presented with conductive hearing loss or mixed hearing loss predominantly of the conductive type, with an intact tympanic membrane. The diagnosis of CAOW was confirmed via endoscopic tympanotomy, revealing a concave oval window area on the medial wall of the tympanic cavity, sealed by a bony plate. All 8 ears exhibited additional ossicular chain deformities. Stapes absence was present in all 8 ears. Partial absence of the incus long process was observed in 3 ears, while, abnormal bony connections between the incus long process and the promontory were seen in 4 ears, 1 ear had a short malleolar handle, 1 ear had a smaller than normal malleus volume. In addition, facial nerve deformities were found in 6 ears, with 4 ears showing bifurcation of the facial nerve and 2 ears showing facial nerve obscuration of the oval window. Pure-tone audiometry revealed that 62.5% (5/8 ears) of patients had air conduction (AC) thresholds≥60 dB preoperatively, with a mean pure-tone average (PTA) of (69.0±11.8) dB HL and a mean air-bone gap (ABG) of (52.0±7.0) dB. The mean AC threshold and ABG were higher in the low-frequency (125-1 000 Hz) range compared to the high-frequency (2 000-8 000 Hz) range (both P<0.05). Preoperative HRCT showed abnormalities in all patients, with 7 ears being diagnosable as CAOW. Although the remaining 1 ear could not be diagnosed as CAOW, stapes and incus long process absence were detected. Conclusion:CAOW is rare in clinical, as the patients with non-progressive conductive hearing loss (AC≥60 dB, ABG≥50 dB) since childhood, intact tympanic membrane without malformations of auricle and external auditory canal, and thick bony plate covered the oval window of the HRCT imaging, CAOW should be highly suspected, which could be confirmed by the exploratory tympanotomy.
7.Effects of 1,8-cineole on inflammatory response in a rat model of experimental periodontitis
Li HE ; Lu REN ; Xiaoxi JIANG ; Xuqian LIU ; Chunhui LI
Chinese Journal of Tissue Engineering Research 2025;29(17):3605-3613
BACKGROUND:Previous studies have shown that 1,8-cineole has anti-inflammatory,antioxidation,antibacterial and anti-tumor effects.It has good anti-inflammatory effects in many diseases.OBJECTIVE:To investigate the effect of 1,8-cineole on inflammatory response in a rat model of experimental periodontitis.METHODS:Thirty Sprague-Dawley rats were assigned into normal control group,periodontitis control group and 1,8-cineole group with ten rats in each group according to the completely randomized digital table method.Except for the normal control group,rats in the other groups were induced into experimental periodontitis.The periodontitis model was constructed by the orthodontic ligature wire method.Eight weeks after modeling,in the 1,8-cineole group,1,8-cineole was placed into periodontal pockets,twice per day for 4 weeks.In the normal control group and the periodontitis control group,the same amount of normal saline was placed into periodontal pockets,twice per day for 4 weeks.After administration,general observation and periodontal clinical indicators were performed.Hematoxylin-eosin staining was used for periodontal histological evaluation.The expressions of inflammatory factors in the serum and gingiva at mRNA and protein levels were detected.RESULTS AND CONCLUSION:(1)Compared with the normal control group,rats in the periodontitis control group showed increased gingival bleeding index and periodontal probing depth(P<0.05),increased serum levels of interleukin 1β,tumor necrosis factor α,and interleukin 6(P<0.05),decreased serum level of interleukin 10(P<0.05),increased mRNA and protein levels of interleukin 1β,tumor necrosis factor α,and interleukin 6 in gingival tissue(P<0.05),and decreased mRNA and protein level of interleukin 10 in gingival tissue(P<0.05).Hematoxylin-eosin staining of periodontal tissues showed that compared with the normal control group,periodontal inflammation was obvious in the periodontitis control group.(2)Compared with the periodontitis control group,rats in the 1,8-cineole group showed decreased gingival bleeding index and periodontal probing depth(P<0.05),decreased serum levels of interleukin 1β,tumor necrosis factor α,and interleukin 6(P<0.05),increased serum level of interleukin 10(P<0.05),decreased mRNA and protein levels of interleukin 1β,tumor necrosis factor α,and interleukin 6 in gingival tissue(P<0.05),and increased mRNA and protein level of interleukin 10 in gingival tissue(P<0.05).Hematoxylin-eosin staining of periodontal tissues showed that compared with the periodontitis control group,periodontal inflammation was remarkably alleviated in the 1,8-cineole group.To conclude,1,8-cineole can attenuate the inflammatory response in the rat model of experimental periodontitis.
8.Study on the mechanistic role of the Fuzheng Huayu formula against cholestatic liver fibrosis in mice
Zheng ZHANG ; Yue LIANG ; Enqi TANG ; Xiaoxi ZHOU ; Yonghong HU ; Gaofeng CHEN ; Wei LIU ; Yongping MU ; Ping LIU ; Jiamei CHEN
Chinese Journal of Hepatology 2025;33(9):889-897
Objective:To investigate the interventional effects of the Fuzheng Huayu (FZHY) formula and its partial mechanistic role on cholestatic liver fibrosis in mice.Methods:Mdr2 gene knockout (Mdr2-/ -) mice were randomly divided into a model group, FZHY group, and Obeticholic acid group. Wild-type C57BL/6J mice of the same age served as the control group. Mdr2-/ -mice were given the corresponding drugs starting from the first day of 9 weeks of age by oral gavage in each group. The control and model groups were administered 0.3% sodium carboxymethylcellulose by oral gavage and were sacrificed at 12 weeks of age for specimen collection. High-speed biochemistry analyzer was used to detect serum alkaline phosphatase and alanine aminotransferase activity in mice. Hematoxylin-eosin staining and Sirius red staining were used to observe pathological changes in liver tissues. Hydroxyproline content was measured to assess collagen in liver tissues. Immunohistochemical staining, Western blotting, and real-time fluorescence quantitative PCR were used to detect the expression of fibrosis markers Col-I and alpha-smooth muscle actin in liver tissues. The expressional condition of cholangiocyte response markers Epcam, CK7, CK19, as well as Pcna, Mki67, and Ccnd1, inflammatory related factors Ccl2, Ccl5, Tnf-α, Il10, and Cxcl4, phosphorylated peroxisome proliferator-activated receptor alpha (PPARα) and nuclear factor kappa-B (NF-κB) were determined. Comparative analysis among multiple groups was performed using one-way ANOVA. The LSD method was used for comparisons between groups. Two-tailed statistical tests were used.Results:Compared with wild-type mice, Mdr2 -/ - mice had a significant increase in serum alanine aminotransferase and alkaline phosphatase activity ( P<0.001). The percentage of Sirius red-positive staining areas and hydroxyproline content in liver tissues was significantly increased ( P<0.01). The expression of Col-I, α-smooth muscle actin, Epcam, CK7, CK19, Pcna, Mki67, and Ccnd1, and the expression of Ccl2, Ccl5, Tnf-α, Il10, and Cxcl4 were significantly increased ( P<0.01); however, both FZHY and Obeticholic acid significantly reversed the increases in these indicators ( P<0.05; P<0.01). Further results showed that compared to wild-type mice, the expression of PPARα was significantly reduced in liver tissues of Mdr2 -/ - mice, while NF-κB was significantly enhanced ( P<0.01). In contrast, compared to Mdr2-/- mice, the expression of PPARα in the liver tissues of FZHY group mice was significantly increased ( P<0.05), while NF-κB was significantly inhibited ( P<0.05). Conclusion:FZHY can significantly improve liver fibrosis, cholangiocyte response, and inflammation in Mdr2 -/ - mice with spontaneously occurring cholestatic liver fibrosis, and its mechanistic role is related to the regulation of the PPARα/NF-κB pathway.
9.Treatment of Parkinson's Disease with Traditional Chinese Medicine by Regulating BDNF/TrkB Signaling Pathway: A Review
Lulu JIA ; Ying LI ; Jiale YIN ; Nan JIA ; Xiaoxi LIU ; Li LING
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):315-322
Parkinson's disease(PD) is the second most common neurodegenerative disease in the world, which seriously affects the lives of patients. With the acceleration of aging process, the number of patients continues to rise. Its main pathological features are aggregation of α-synuclein and degenerative death of dopaminergic neurons in the substantia nigra. However, the pathogenesis of PD is still unclear. According to reports, the brain-derived neurotrophic factor(BDNF)/tyrosine kinase receptor B(TrkB) signaling pathway is highly expressed and activated in dopaminergic neurons in the substantia nigra, which is closely related to neurophysiological processes such as neurogenesis, synaptic plasticity, neuroinflammation, and oxidative stress. It plays an important role in the occurrence and development of PD. At present, the treatment methods of Western medicine for PD are mainly based on drugs such as levodopa and dopamine agonists to alleviate motor symptoms, but with the increase of dose, the adverse reactions are significantly enhanced. Traditional Chinese medicine(TCM) has attracted people to explore its therapeutic effects on PD due to its characteristics of homology of medicine and food, economy, minor adverse reactions and multi-target action. Therefore, this paper systematically reviews the role of BNDF/TrkB pathway in the pathogenesis of PD and the mechanism of TCM formulas, extracts and monomers in the treatment of PD by regulating the BNDF/TrkB pathway according to retrieving the latest research reports at home and abroad, so as to provide a reference for the clinical application of related TCM and the development of new drugs for PD.
10.Regulation of autophagy on diabetic cataract under the interaction of glycation and oxidative stress
Rong WANG ; Pengfei LI ; Jiawei LIU ; Yuxin DAI ; Mengying ZHOU ; Xiaoxi QIAN ; Wei CHEN ; Min JI
International Eye Science 2025;25(12):1932-1937
Diabetic cataract, a prevalent ocular complication of diabetes mellitus, arises from a complex interplay of pathological mechanisms, with oxidative stress and glycation stress playing central roles. Autophagy, a critical cellular self-protection mechanism, sustains intracellular homeostasis by selectively degrading damaged organelles and misfolded proteins, thereby counteracting the detrimental effects of oxidative and glycation stress under hyperglycemic conditions. Emerging evidence indicates a synergistic interaction between glycation stress and oxidative stress, which may exacerbate autophagic dysfunction and accelerate the onset and progression of diabetic cataract. However, the precise molecular mechanisms underlying this relationship remain incompletely understood. This review systematically examines the regulatory role of autophagy inthe pathogenesis of diabetic cataract, with a particular focus on how autophagic impairment influences disease progression under the combined effects of glycation and oxidative stress. By elucidating these mechanisms, the paper aims to provide novel insights into molecular diagnostic approaches and targeted therapeutic strategies for diabetic cataract.

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