CHEMICAL ENGINEERING JOURNAL
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2020
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IF 10.652
Huachu Wu,Liang Shen,Zhu Zhu,Xusong Luo,Yishu Zhai,Xiaobin Hua,Shicheng Zhao,Lian Cen,Zhibing Zhang
This study was to co-encapsulate a chemokine (stromal cell-derived factor-1, SDF-1) and a chondroinductive molecule (kartogenin, KGN) within microspheres via microfluidics, and to incorporate them into a hyaluronic acid (HA) injectable scaffold for articular cartilage defect repair. HA injectable scaffold, as a cartilage-friendly microenvironment, was prepared by crosslinking HA with 1,4-butanediol diglycidyl ether. A microfluidic device was set up to prepare monodisperse PLGA microspheres (49 μm) to load SDF-1 and KGN. An in vivo model of full-thickness articular cartilage defects in rabbits was applied to evaluate the reparative capacity of the current package. The SDF-1 and KGN were co-encapsulated simultaneously within the core and shell area of the microsphere with high loading efficiency and sustained release profiles of more than 2 months. The release profiles of them were highly matched and well fitted to a first-order mathematical model. These microspheres when incorporated into HA injectable scaffold were demonstrated to heal the full-thickness articular cartilage defects in rabbits. The regenerated tissue had the typical cartilage histological characters and integrated well with the surrounding tissue at 12w. This developed cell-free system could serve as an efficient therapy for articular cartilage defects treatment, serving as a supplementary way to cell based therapies.
研究领域:
生物医学工程
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组织工程
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骨科
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DOI
高影响因子
CELLULAR AND MOLECULAR BIOLOGY
·
2024
·Vol. 70
·期 2
·257-263
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IF 1.5
Qingzhi Wan,Lisha Tang,Kaili Jin,Xuanyi Chen,Yinghuan Li,Xiaofeng Xu
Granulosa cells are somatic cells located inside follicles that play a crucial role in the growth and development of follicles. Quercetin and tanshinone are two key monomers in traditional Chinese medicine that have antioxidant and anti-aging properties. The KGN cell apoptosis model caused by triptolide (TP) was employed in this work to investigate granulosa cell death and medication rescue. Quercetin and tanshinone therapy suppressed KGN cell death and oxidation while also regulating the expression of critical apoptosis and oxidation-related markers such as B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax). Further research revealed that the effects of Quercetin and Tanshinone were accomplished via deacetylation of FOXO3A in the cytoplasm and mitochondria via the SIRT1/SIRT3-FOXO3a axis. In summary, Quercetin and tanshinone protect KGN cells from apoptosis by reducing mitochondrial apoptosis and oxidation via the SIRT1/SIRT3-FOXO3a axis.
研究领域:
药理学
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细胞生物学
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中医药
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生殖生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2024
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IF 4.4
Li Tian,Wei Yao,Jiao Beibie,Hao Rui,Zhou Beibei,Bian Xinlan,Wang Peijuan,Zhou Yahong,Sun Xia,Zhang Jian
Introduction: Premature ovarian insufficiency (POI) has affected about 3.7% of women of reproductive age and is a major factor contributing to infertility. Bushen Huoxue formula (BHF), a traditional Chinese medicine prescription, is clinically used to treat POI in China. This study aims to investigate the potential mechanisms of BHF in combating POI using corticosterone-induced rats and palmitic acid (PA)-challenged human ovarian granulosa cells (GCs).Methods: Initially, ultra performance liquid chromatography tandem mass spectrometry was employed to analyze the components of BHF. The pharmacodynamic parameters evaluated included body weight, ovaries index, and serum hormone in rats. Follicle numbers were observed using H&E staining. Additionally, PCNA and TUNEL staining were used to assess GCs proliferation and apoptosis, respectively. Lipid accumulation and ROS levels were examined using Oil Red O and ROS staining. Protein expressions were determined by western blot. To probe mechanisms, cell viability and E2 levels in BHF-treated, PA-stimulated GCs were determined using MTT and ELISA, respectively. Cell apoptosis and ROS levels were assessed using TUNEL and ROS staining. Proteins related to lipid metabolism and autophagy in PA-stimulated GCs were studied using agonists.Results: Our results shown that BHF effectively normalized serum hormone levels, including follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), estradiol (E2), and luteinizing hormone (LH). Concurrently, BHF also significantly reduced follicular atresia and promoted cell proliferation while inhibiting apoptosis in POI rats. Furthermore, BHF mitigated ovarian lipid accumulation by modulating lipid metabolism, which included reducing lipid synthesis (expression of peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α), increasing lipid catabolism (expression of adipose triglyceride lipase), and enhancing lipid oxidation (expression of carnitine palmitoyl transferase 1A). Mechanistically, the therapeutic effects of BHF on POI were linked with alleviation of lipid deposition-induced reactive oxygen species (ROS) accumulation and excessive autophagy, corroborating the results in PA-challenged GCs. After treatment with elesclomol (a ROS inducer) and rapamycin (an autophagy inducer) in GCs, the effects of BHF were almost counteracted under model conditions.Conclusion: These findings suggest that BHF alleviates the symptoms of POI by altering lipid metabolism and reducing lipid accumulation-induced ROS and autophagy, offering evidence for BHF’s efficacy in treating POI clinically.
研究领域:
药理学
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内分泌学
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中医
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细胞生物学
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生殖医学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2026
·
IF 6.2
Zhenbiao Wangzi,Chengcheng Yang,Peng Yu,Xiubiao Huang,Nan Hu,Tuo Jiao,Hao Qi
Osteochondral defects require the simultaneous regeneration of cartilage and subchondral bone, posing a major challenge for current biomaterial strategies. Here, we present a radially oriented 3D-printed bilayer hydrogel scaffold composed of a mechanically reinforced GelMA/HAP osteogenic layer and a compliant, KGN@Lip-loaded GelMA chondrogenic layer, to achieve coordinated osteochondral repair. Structural and physicochemical characterization confirmed the formation of a functionally graded architecture with uniform HAP and KGN@Lip distribution, while mechanical, rheological, swelling, and degradation analyses revealed a layer-dependent gradient that resembles certain structural features of the native osteochondral interface. In vitro, the GelMA/HAP layer promoted robust osteogenic differentiation through ion-mediated activation of osteogenic pathways, whereas the GelMA/KGN@Lip layer sustained chondrogenic stimulation and markedly enhanced SOX9, Col2a1, and Acan expression. The radially oriented microchannels provided an interconnected structure that may support nutrient transport and cell infiltration. In vivo implantation demonstrated substantial subchondral bone regeneration and the formation of cartilage-like tissue with improved matrix organization, along with enhanced integration at the osteochondral interface, confirming the scaffold's ability to provide spatially coordinated biochemical and structural cues. Overall, this anisotropic bilayer hydrogel scaffold offers a promising strategy for integrated and functional osteochondral regeneration.
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DOI
PubMed
高影响因子
Theranostics
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2020
·
IF 8.579
Yuping Hong,Yaguang Han,Jun Wu,Xinxin Zhao,Jin Cheng,Guo Gao,Qirong Qian,Xiuying Wang,Weidong Cai,Hala Zreiqat,Dagan Feng,Jianrong Xu,Daxiang Cui
Chondral and osteochondral defects caused by trauma or pathological changes, commonly progress into total joint degradation, even resulting in disability. The cartilage restoration is a great challenge because of its avascularity and limited proliferative ability. Additionally, precise diagnosis using non-invasive detection techniques is challenging, which increases problems associated with chondral disease treatment. Methods: To achieve a theranostic goal, we used an integrated strategy that relies on exploiting a multifunctional nanoprobe based on chitosan-modified Fe3O4 nanoparticles, which spontaneously self-assemble with the oppositely charged small molecule growth factor, kartogenin (KGN). This nanoprobe was used to obtain distinctively brighter T 2 -weighted magnetic resonance (MR) imaging, allowing its use as a positive contrast agent, and could be applied to obtain accurate diagnosis and osteochondral regeneration therapy. Results: This nanoprobe was first investigated using adipose tissue-derived stem cells (ADSCs), and was found to be a novel positive contrast agent that also plays a significant role in stimulating ADSCs differentiation into chondrocytes. This self-assembled probe was not only biocompatible both in vitro and in vivo , contributing to cellular internalization, but was also used to successfully make distinction of normal/damaged tissue in T 2 -weighted MR imaging. This novel combination was systematically shown to be biosafe via the decrement of apparent MR signals and elimination of ferroferric oxide over a 12-week regeneration period. Conclusion: Here, we established a novel method for osteochondral disease diagnosis and reconstruction. Using the Fe 3 O 4 -CS/KGN nanoprobe, it is easy to distinguish the defect position, and it could act as a tool for dynamic observation as well as a stem cell-based therapy for directionally chondral differentiation.
研究领域:
生物医学工程
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材料科学
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再生医学
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医学影像
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Xinding Yu,Jian Wang,Shenglai Zhou,Peng Pan,Tiantian Chen,Xi Wang,Wentao Liu
Due to the extreme difficulty of cartilage, we endeavored to fabricate a novel biodegradable scaffold using natural polysaccharide cellulose and poly(lactic- co -glycolic acid) (PLGA) microspheres incorporating controllably released the cartilage inducer kartogenin (KGN) for enhancing regenerative healing in cartilage tissue. Initially, to facilitate the loading of KGN, PLGA/KGN microspheres were fabricated using the solvent volatilization method. These microspheres exhibited high sphericity, with particle sizes diminishing from 12.11 to 3.27 μm as the emulsification rate increased. Demonstrating adequate encapsulation efficiency, the microspheres enabled controlled drug release, positively influencing cell migration and recruitment. Subsequently, a biodegradable cellulose composite scaffold loaded with PLGA/KGN microspheres was prepared using the freeze-drying method. Compared with pure MCC scaffolds, composite scaffolds had a lower degradation rate, and the incorporation of microspheres promoted cell proliferation and significantly elevated expression of cartilage-related specific genes. In a rat cartilage defect model, it was further demonstrated that the composite scaffold combined with stem cell implantation achieved an optimal repair effect, characterized by vigorous extracellular matrix secretion and increased maturity of the regenerated cartilage tissues, suggesting potential clinical application value as a novel articular cartilage repair product in the future.
研究领域:
组织工程学
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再生医学
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材料科学
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产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
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2026
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IF 8.7
Huang Jian,Tang Chen,Wu Ye,Xiang Tao,Chen Keyi,Bao Xiaogang,Wang Bo,Ren Jie,Yin Jingbo,Yan Shifeng,Xu Guohua
Articular cartilage has limited self-repair ability, and effective therapies for defects remain challenging. Injectable hydrogels are attractive for cartilage tissue engineering as they can fill irregular defects and mimic the native extracellular matrix (ECM). However, current hydrogels often suffer from dense microstructures, poor mechanical stability, and inadequate biological signaling, restricting tissue regeneration. In this study, a multifunctional injectable hydrogel system based on oxidized dextran and carboxymethyl chitosan (ODex/CMCS) was developed by integrating degradable gelatin microspheres (GMs) and kartogenin-loaded crosslinked gelatin fibers (KGN@GFs). The GMs served as thermosensitive, dissolvable porogens that generated an interconnected porous structure within the hydrogels to enhance nutrient diffusion, cell infiltration, and tissue ingrowth, while the KGN@GFs provided sustained KGN release and additional mechanical reinforcement. The resulting composite hydrogels exhibited favorable injectability, self-healing capability, and a porous architecture conducive to cell survival and spatial organization. In vitro experiments demonstrated good cytocompatibility and significantly enhanced chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Furthermore, implantation in rabbit cartilage defect models revealed that the ODex/CMCS/KGN@GFs/GMs hydrogel effectively promoted hyaline-like cartilage regeneration and integration with surrounding tissue. Collectively, this work presents a structurally and functionally optimized injectable hydrogel system that synergistically combines biochemical and structural cues to promote cartilage repair.
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DOI
高影响因子
Bioengineering & Translational Medicine
·
2022
·Vol. 8
·期 1
·e10364
·
IF 10.684
Chuyao Chen,Shaoshan Huang,Zelong Chen,Qin Liu,Yu Cai,Yingjie Mei,Yikai Xu,Rui Guo,Chenggong Yan
Cartilage regeneration after injury is still a great challenge in clinics, which suffers from its avascularity and poor proliferative ability. Herein we designed a novel biocompatible cellulose nanocrystal/GelMA (gelatin-methacrylate anhydride)/HAMA (hyaluronic acid-methacrylate anhydride)-blended hydrogel scaffold system, loaded with synthetic melanin nanoparticles (SMNP) and a bioactive drug kartogenin (KGN) for theranostic purpose. We found that the SMNP-KGN/Gel showed favorable mechanical property, thermal stability, and distinct magnetic resonance imaging (MRI) contrast enhancement. Meanwhile, the sustained release of KGN could recruit bone-derived mesenchymal stem cells to proliferate and differentiate into chondrocytes, which promoted cartilage regeneration in vitro and in vivo. The hydrogel degradation and cartilage restoration were simultaneously monitored by multiparametric MRI for 12 weeks, and further confirmed by histological analysis. Together, these results validated the multifunctional hydrogel as a promising tissue engineering platform for noninvasive imaging-guided precision therapy in cartilage regenerative medicine.
研究领域:
生物材料学
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再生医学
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医学影像学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2020
·Vol. 24
·期 18
·11001-11011
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IF 4.486
Jun Liu,Jinli Ding,Bing Qu,Jiuying Liu,Xiaojie Song,Qingli Suo,Aifen Zhou,Jing Yang
Polycystic ovary syndrome (PCOS), the most common female endocrine disease that causes anovulatory infertility, still lacks promising strategy for the accurate diagnosis and effective therapeutics of PCOS attributed to its unclear aetiology. In this study, we determined the abnormal reduction in circPSMC3 expression by comparing the ovarian tissue samples of PCOS patients and normal individuals. The symptom relief caused by up-regulation of circPSMC3 in PCOS model mice suggested the potential for further study. In vitro functional experiments confirmed that circPSMC3 can inhibit cell proliferation and promote apoptosis by blocking the cell cycle in human-like granular tumour cell lines. Mechanism study revealed that circPSMC3 may play its role through sponging miR-296-3p to regulate PTEN expression. Collectively, we preliminarily characterized the role and possible insights of circPSMC3/miR-296-3p/PTEN axis in the proliferation and apoptosis of KGN cells. We hope that this work provides some original and valuable information for the research of circRNAs in PCOS, not only to better understand the pathogenesis but also to help provide new clues for seeking for the future therapeutic target of PCOS.
研究领域:
妇科学
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分子生物学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
LANGMUIR
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2020
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IF 3.557
Yiqun Wang,Yuan Yao
In natural tissue, nanofibrils in extracellular matrix (ECM), such as collagen fibrils, direct cell migration through contacting guidance. The contacting nanofibers on cell-ECM interface are reorganized from curl fibers to straightened fibers. However, how these nanofibers regulate single cell migration remains obscure. To investigate this issue, we fabricated collagen/polymer based biomimetic nanofiber sheets of varying topography. And we selected tumorigenic cell KGN and nontumorigenic cell 293T for comparison. We found KGN showed higher sensitivity to the nanofiber alignment rather than the nontumorigenic cell 293T, in morphological change, trajectory adaptation, and velocity variation. We also found aligned nanofibers shaped both KGN and 293T into elongated spindle morphology. Comparatively, KGN had greater perimeter and lower roundness than 293T. To study the dynamics of single cell migration of KGN and 293T, we conducted trajectory tracking and siRNA validation on regulatory proteins. We found nanofibers of varying topography regulated the patterns of single cell migration differently. For KGN cell, β-catenin, Rac1, and Cdc42 participated in its directional migration, but it was impervious to vimentin. Comparatively, epithelial cell 293T involved vimentin in its directional migration.
研究领域:
生物材料
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细胞生物学
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组织工程
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产品关联
DOI
PubMed
高影响因子
Human Cell
·
2024
·
IF 3.4
Guo Xiaoli,Cao Yijuan,He Qing,Chen Linna,Wang Qing,Zhang Jingbo,Lv Wenqiang,Zhang Bei,Zhou Xueyan
Polycystic ovary syndrome (PCOS) is a complex gynaecological endocrine disease that occurs in women of childbearing age. The pathogenesis of PCOS is still unclear and further exploration is needed. Here, proteomic analysis indicated that the expression of farnesyl diphosphate synthase (FDPS) protein in ovarian tissue of PCOS mice was significantly decreased. The purpose of this study is to investigate the relationship between potential biomarkers of PCOS and granulosa cells (GCs) function. The mechanisms by which FDPS affected the proliferation of granulosa cells were also explored both in vitro and in vivo. We found that knockdown of FDPS inhibited the proliferation of KGN (human ovarian granulosa cell line), while overexpression of FDPS had the opposite effect. FDPS activated Rac1 (Rac Family Small GTPase 1) activity and regulated MAPK/ERK signalling pathway, which affecting the proliferation of KGN cells significantly. In addition, treatment with the adeno-associated virus (AAV)-FDPS reverses the dehydroepiandrosterone (DHEA)-induced PCOS-phenotype in mice. Our data indicated that FDPS could regulate the proliferation of ovarian GCs by modulating MAPK/ERK (mitogen-activated protein kinase/extracellular regulated protein kinases) pathway via activating Rac1 activity. These findings suggest that FDPS could be of great value for the regulation of ovarian granulosa cell function and the treatment of PCOS.
研究领域:
妇科学
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内分泌学
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分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2022
·
IF 3.322
Jing Cong,Yuehui Zhang,Xinming Yang,Yu Wang,Hui He,Mengying Wang
Polycystic ovary syndrome (PCOS) is a complicated endocrinopathy affecting women at reproductive age. Increasing evidence has shown the anti-PCOS effect of electroacupuncture (EA), a modified approach of traditional Chinese medical therapy “acupuncture”. However, the underlying mechanism of EA-alleviated PCOS waits further explored. In this study, experimental PCOS were induced in rats by dehydroepiandrosterone (DHEA) injection. Testosterone (T)-induced human ovarian granulosa cell (GC) line KGN was used to mimic PCOS in vitro . EA significantly alleviated histological changes and hormone disruption in PCOS rats. Besides, EA inhibited cell apoptosis, autophagy and the activation of endoplasmic reticulum (ER) stress-related PERK/eIF2α/ATF4/CHOP signaling in ovaries of PCOS rats. More interestingly, intermedin (IMD), a member of calcitonin gene-related peptide (CGRP), was evidently up-regulated in ovarian GCs after EA treatment, and its main bioactive form IMD 1-53 suppressed cell apoptosis, autophagy and PERK/eIF2α/ATF4/CHOP signaling in T-induced KGN cells. Consistent with IMD 1-53 , ER stress inhibitor 4-PBA exerted an inhibitory effect on T-induced cell apoptosis and autophagy in KGN cells. Collectively, this study validates the protective effect of EA on DHEA-induced PCOS, and proposes that IMD relieved apoptosis and autophagy in T-induced granulosa cells via inhibiting ER stress.
研究领域:
生殖医学
·
内分泌学
·
分子生物学
·
中医学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）