Materials Today Bio
·
2025
·
IF 10.2
Yuan Wang,Zhen Pan,Qianliang Wang,Yuexia Shu,Zhenyu Tan,Yujie Chen,Jieming He,Jia Wang,Jielin Wang,Jun Yan
Osteoporotic fractures typically exhibit delayed healing due to impaired cell recruitment, chronic inflammation, and disrupted neurovascular signaling. Sensory nerve signaling plays a crucial role in fracture repair, and its deficiency is a significant factor leading to delayed healing. Addressing these deficiencies is crucial to overcoming the challenges associated with delayed bone repair in osteoporosis. In this study, a smart composite hydrogel (denoted as OCS-MPC) was synthesized by embedding CGRP-functionalized polydopamine-coated MXene nanosheets (MXene/PDA/CGRP) into boronic acid-modified oxidized hyaluronic acid-crosslinked carboxymethyl chitosan (OHA-PBA/CMCS) hydrogel loaded with SDF-1. OCS-MPC hydrogel enables the controlled release of SDF-1 and CGRP, aiming to promote early callus formation and late-stage callus remodeling in osteoporotic fractures. Due to dynamic crosslinking via imine and borate ester bonds, OCS-MPC exhibits rapid gelation, injectability, and self-healing properties. In vitro experiments demonstrated excellent osteogenic, angiogenic, and neurogenic properties of OCS-MPC hydrogel. In vivo studies using an osteoporotic femoral fracture model showed that OCS-MPC hydrogel enhanced MSCs recruitment via the SDF-1/CXCR4 signaling axis, significantly improving callus formation in the early stages of fracture repair. Additionally, OCS-MPC hydrogel significantly promoted callus mineralization and remodeling in the later stages of osteoporotic fracture healing through enhancing CGRP signaling. Immunofluorescence analysis further confirmed increased expression of TUBB3, CGRP, and CD31, indicating successful regeneration of the neurovascular network. These findings highlight the potential of OCS-MPC hydrogel in addressing both early and late-stage challenges of osteoporotic fracture healing, providing a promising therapeutic strategy for enhancing bone regeneration in osteoporotic patients.
研究领域:
生物医学工程
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骨科
·
再生医学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2020
·
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
·
骨科
✓ 已验证
DOI
高影响因子
BIOMATERIALS
·
2016
·
IF 8.387
Xiaofeng Shen,Yanxia Zhang,Yong Gu,Yun Xu,Yong Liu,Bin Li,Liang Chen
In this study, a cell-free bone tissue engineering system based on a silk fibroin (SF)/nano-hydroxyapatite (nHAp) scaffold was developed, in which two bioactive molecules , stromal cell derived factor-1 (SDF-1) and bone morphogenetic protein-2 (BMP-2), were embedded and released in a sequential and controlled manner to facilitate cell recruitment and bone formation, respectively. BMP-2 was initially loaded into SF microspheres , and these BMP-2 containing microspheres were subsequently encapsulated into the SF/nHAp scaffolds, which were successively functionalized with SDF-1 via physical adsorption. The results indicated rapid initial release of SDF-1 during the first few days, followed by slow and sustained release of BMP-2 for as long as three weeks. The composite scaffold significantly promoted the recruitment of bone marrow mesenchymal stem cells (BMSCs) and osteogenic differentiation of them in vitro . Further, the in vivo studies using D-Luciferin-labeled BMSCs indicated that implantation of this composite scaffold markedly promoted the recruitment of BMSCs to the implanted sites. Enhanced bone regeneration was identified at 12 weeks' post-implantation. Taken together, our findings suggested that the sequential and sustained release of SDF-1 and BMP-2 from the SF/nHAp scaffolds resulted in a synergistic effect on bone regeneration. Such a composite system , therefore, shows promising potential for cell-free bone tissue engineering applications .
研究领域:
生物医学工程
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组织工程
·
再生医学
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DOI
PubMed
高影响因子
ANNALS OF BIOMEDICAL ENGINEERING
·
2020
·Vol. 48
·期 5
·1511-1523
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IF 3.324
Ding Yilei,Zhao An-sha,Liu Tianmei,Wang Ya-nan,Gao Yuan,Li Jing-an,Yang Ping
In this contribution, an injectable hydrogel was developed with chitosan, gelatin, β-glycerphosphate and Arg-Gly-Asp (RGD) peptide: this hydrogel is liquid in room temperature and rapidly gels at 37 °C; RGD peptide promises better growth microenvironment for various cells, especially endothelial cells (EC), smooth muscle cells (SMC) and mesenchymal stem cells (MSC). Both stromal cell-derived factor-1 (SDF-1) nanoparticle and vascular endothelial growth factor (VEGF) nanoparticles were loaded in the injectable hydrogel to simulate the natural nanoparticles in the extracellular matrix (ECM) to promote angiogenesis. In vitro EC/SMC and MSC/SMC co-culture experiment indicated that the nanocomposite hydrogel accelerated constructing embryonic form of blood vessels, and chick embryo chorioallantoic membrane model demonstrated its ability of improving cells migration and blood vessel regeneration. We injected this nanocomposite hydrogel into rat myocardial infarction (MI) model and the results indicated that the rats heart function recovered better compared control group. We hope this injectable nanocomposite hydrogel may possess wider application in tissue engineering.
研究领域:
生物材料学
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再生医学
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心血管研究
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组织工程
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2022
·Vol. 11
·期 21
·2201457
·
IF 11.092
Yingji Mao,Yu Chen,Weifeng Li,Ying Wang,Jingjing Qiu,Yingxiao Fu,Jianzhong Guan,Pinghui Zhou
Bone regeneration involves a cascade of sophisticated, multiple-staged cellular and molecular events, where early-phase stem cell recruitment mediated by chemokines and late-phase osteo-differentiation induced by pro-osteogenic factors play the crucial roles. Herein, enlightened by a bone physiological and regenerative mechanism, the multilayer nanofibrous membranes (PLLA@SDF-1 α @MT01) consisting of PLLA/MT01 micro-sol electrospun nanofibers as intima and PLLA/PEG/SDF-1 α electrospun nanofibers as adventitia are fabricated through micro-sol electrospinning and manual multi-layer stacking technologies. In vitro releasing profiles show that PLLA@SDF-1 α @MT01 represents the rapid release of stromal cell-derived SDF-1 α (SDF-1 α ) in the outer layers, while with long-term sustained release of MT01 in the inner layer. Owing to interconnected porosity like the natural bone extracellular matrix and improved hydrophilia, PLLA@SDF-1 α @MT01 manifests good biocompatibility both in vitro and in vivo. Furthermore, PLLA@SDF-1 α @MT01 can promote bone marrow mesenchymal stem cells (BMSCs) migration by amplifying the SDF-1 α /CXCR4 axis and stimulating BMSCs osteo-differentiation via activating the MAPK pathway in vitro. PLLA@SDF-1 α @MT01, with a programmed dual-delivery system, exhibits the synergetic promotion of bone regeneration and vascularization by emulating key characteristics of the staged bone repair in vivo. Overall, PLLA@SDF-1 α @MT01 that mimics the endogenous cascades of bone regeneration can enrich the physiology-mimetic staged regenerative strategy and represent a promising tissue-engineered scaffold for the bone defect.
研究领域:
组织工程
·
再生医学
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生物材料
·
干细胞生物学
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骨科
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biochemistry Research International
·
2020
·
IF 0
Yaoyv Xiang,Yanlin Li,Lingjian Yang,Yinghong He,Di Jia,Xidan Hu
Osteoarthritis (OA) is a chronic joint function disorder with characteristics of chondrocytes reduction and extracellular matrix (ECM) components destruction. MicroRNAs (miRNAs) and the SDF-1/CXCR4 axis are essential factors of chondrocyte apoptosis and ECM degeneration. However, very few studies have investigated the correlation between miRNAs and the SDF-1/CXCR4 axis in osteoarthritis so far. Here, through miRNAs microarray and bioinformatics analyses, we identified miR-142-5p as a CXCR4-targeted and dramatically downregulated miRNA in cartilage from OA patients, as well as in SDF-1-induced OA chondrocytes in vitro. In SDF-1-treated primary human OA chondrocytes that were transfected with a miR-142-5p mimic or inhibitor, the expression of CXCR4 was found to be inversely correlated with the expression of miR-142-5p. The dual luciferase reporter assay further verified the target relationship between miR-142-5p and CXCR4. Overexpression of miR-142-5p alleviated OA pathology by suppressing chondrocyte apoptosis, even in CXCR4 overexpressed OA chondrocytes. This was associated with decreased cartilage matrix degradation, reduced cartilage inflammation, and inactivated MAPK signaling pathway. Our study suggests that upregulated expression of CXCR4-targeted miR-142-5p can inhibit apoptosis, inflammation, and matrix catabolism and inactivate the MAPK signaling pathway in OA chondrocytes. Our work provides important insight into targeting miR-142-5p and the SDF-1/CXCR4 axis in OA therapy.
研究领域:
分子生物学
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风湿病学
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骨科学
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DOI
PubMed
Materials Today Bio
·
2025
·
IF 10.2
Ruifang Han,Haiyi Zhou,Xingshan Liang,Siyi He,Xiaoming Sun,Yongge Guan,Yang Song
Endometrium plays a key role in embryo implantation and maintenance of pregnancy. However, to repair endometrial injury is still a challenge. In recent years, hydrogel materials have been widely used as effective support matrices to prevent intrauterine adhesions after endometrial injury. They can also be used as preparation scaffolds for encapsulating MSCs and certain therapeutic drugs. This study aimed to develop a preparation scaffold with high tissue affinity, high viscoelasticity and controlled release for repair of endometrial injury. The scaffold utilized heparin poloxamer (HP) as the matrix material and ε-polylysine (EPL) as the functional excipient to prepare a hydrogel that is suitable for endometrial adhesion and further encapsulate BMSCs. Furthermore, a strategy of the thermo-sensitive EPL-HP hydrogel-encapsulated BMSCs were used for better homing of BMSC after transplantation into the rat endometrial injury model, so as to exert the potential of endometrial regeneration by activating Nrf2 to regulate SDF-1/CXCR4 axis.
研究领域:
生殖医学
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组织工程
·
干细胞研究
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF HISTOCHEMISTRY
·
2020
·
IF 2.172
Li Wu,Dan Han,Jie Jiang,Xiaojie Xie,Xunran Zhao,Tengfei Ke,Wen Zhao,Liu Liu,Wei Zhao
After the facial nerve axotomy (FNA), the distal end of the axon would gradually decay and disappear. Accumulated evidence shows that transplantation of bone marrow mesenchymal stem cells (BMSCs) reveals potential in the treatment of nervous system diseases or injuries. This study is aimed at investigating the therapeutic effects of co-transplantation of BMSCs and monocytes in FNA. We found that co-culture significantly elevated the CD4+/CD8+ ratio and CD4+ CD25+ T cell proportion compared with monocytes transplantation, and enhanced the differentiation of BMSCs into neurons. After the cell transplantation, the lowest apoptosis in the facial nerve nucleus was found in the co-transplantation group 2 (BMSCs:monocytes= 1:30). Moreover, the lowest expression levels of pro-inflammatory cytokines and the highest expression levels of anti-inflammatory cytokines were observed in the co-transplantation group 2 (BMSCs: monocytes= 1:30). The highest expression levels of protein in the JAK/STAT6 pathway and the SDF-1/CXCR4 axis were found in the co-transplantation group 2. BMSC/monocyte co-transplantation significantly improves the microenvironment in the facial nerve nucleus in FNA rats; therefore these findings suggest that it could promote the anti-/pro-inflammatory balance shift towards the anti-inflammatory microenvironment, alleviating survival conditions for BMSCs, regulating BMSC the chemotaxis homing, differentiation, and the section of BMSCs, and finally reducing the neuronal apoptosis. These findings might provide essential evidence for the in-hospital treatment of FNA with co-transplantation of BMSCs and monocytes.
研究领域:
神经科学
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干细胞生物学
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再生医学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Yinhe Han,Lina Guo,Mingqi Wang,Zhen Cao,Xu Zheng,Xinyu Wang,Lingling Jin,Xiaoqing Wei,Xiuli Wang,Jie Zhao
Interactions among neurons, microglia, and endothelial cells (ECs) —the principal components of the neurovascular unit (NVU)—are vital for maintaining central nervous system (CNS) homeostasis and are implicated in numerous neurological disorders. However, mechanistic insights into their crosstalk remain limited due to the lack of physiologically relevant in vitro models. In this study, we present an improved 3D vascularized tri-culture model that integrates human-induced neural stem cells (hiNSCs), human vascular organoids (hVOs), and microglia within a geometrically engineered silk fibroin scaffold. This platform effectively recapitulates critical features of the native CNS microenvironment, including spatial neurovascular patterning and cell-type-specific interactions. Within this model, hVOs significantly promoted neuronal differentiation of hiNSCs, resulting in extended axonal networks and improved neurovascular alignment. Microglial effects were found to be phenotype-dependent: both resting (M0) and pro-inflammatory (M1) microglia inhibited hiNSCs differentiation and vascular development, with M1 cells exerting the strongest suppressive influence. In contrast, anti-inflammatory (M2) microglia displayed the least inhibitory effect and even modestly supported neurovascular maturation. Mechanistic studies revealed that M2 microglia cooperate with hVOs via the stromal cell-derived factor 1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) signaling axis to promote neuronal differentiation. To our knowledge, this represents the first demonstration of SDF-1/CXCR4-mediated immune-neurovascular interaction within a human tri-culture system. Thereafter, this 3D vascularized co-culture model provides a physiologically relevant in vitro platform to investigate neuroimmune and neurovascular interactions. It holds broad potential for mechanistic studies in neurodevelopment and neurodegeneration, drug evaluation, and the development of regenerative therapies.
研究领域:
神经科学
·
生物工程
·
细胞生物学
·
免疫学
·
发育生物学
·
再生医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
STEM CELLS
·
2021
·Vol. 39
·期 11
·1546-1562
·
IF 6.277
Dong Yuan,Kong Weining,An Wei
Cell-based therapeutic approaches have been proven to be effective strategies for the treatment of acute liver injury (ALI). However, widespread application of these procedures is limited by several key issues, including rapid loss of stemness in vitro, aberrant differentiation into undesirable cell types, and low engraftment in vivo. In this study, liver epithelial progenitor cells (LEPCs) were characterized and transfected with augmenter of liver regeneration (ALR). The results revealed that in ALI mice with CCl4, the transplantation of ALR-bearing LEPCs into the liver markedly protected mice against ALI by decreasing the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), thus relieving hepatic tissue injury and attenuating inflammatory infiltration. Mechanistically, the knockdown of ALR in LEPCs activated the phosphorylation of dynamin-related protein 1 (Drp1) at the S616 site and thereby enhanced mitochondrial fission. In contrast, the transfection of ALR into LEPCs significantly inhibited Drp1 phosphorylation, thereby favoring the maintenance of mitochondrial integrity and the preservation of adenosine triphosphate contents in LEPCs. Consequently, the ALR-bearing LEPCs transplanted into ALI mice exhibited substantially greater homing ability to the injured liver via the SDF-1/CXCR4 axis than that of LEPCs-lacking ALR. In conclusion, we demonstrated that the transplantation of ALR-transfected LEPCs protected mice against CCl4-induced ALI, thus offering immense curative potential in the clinic.
研究领域:
肝病学
·
干细胞生物学
·
分子生物学
·
细胞治疗
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Lu Yang,Tingwei Gu,Yang Xu,Yuda Liu,Yongping Zhang,Zhihong Jiang,Lihua Peng
Natural polysaccharides derived from medicinal plants , that are Dendrobium (DPS), Lycium barbarum (LBP), Ginseng (GPS), and Poria Cocos (PCP) were firstly combined with sodium alginate (SA) to construct microcapsules and improved the morphology, encapsulation efficiency, Biocompatibility and protective capability in drug loading. Diverse typical therapeutics, including VO 2 @ZIF67 nanoparticles , small molecule drugs salvianolic acid B (SaB)/ginsenoside (Rg1), probiotic Bacillus bifidus , and biomacromolecules SDF-1 were wrapped into 1.5 % GPS-0.5 % SA model microcapsules, respectively. Better mobility and formability were significantly observed, and showed 75 % survival rate of probiotics in simulated gastric juice and around 99 % encapsulation efficiency which is higher than single 2 % SA microcapsules. The microcapsules also obtained a delayed release and a higher cell index for SDF-1, which indicated better stability, biocompatibility and protective effect than single 2 % SA microcapsules. This study provides a strategy in developing plant derived polysaccharides as novel materials for the construction and improvement of traditional microcapsules.
研究领域:
药学
·
材料科学
·
生物技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2020
·
IF 7.727
Xue Yang,Fang Gao,Wenan Zhang,Huipeng Li,Xinzhi Huang,Jiajia Wei,Jiayi Bian,Ying Yang,Chenggen Qian,Minjie Sun
Invasion and metastasis of tumor cells is one of the major obstacles in cancer therapy. The process of tumor metastasis and diffusion is coordinated by multiple pathways associated with chemokine signals and migration microenvironment. In our previous work, chemokine CXC receptor 4 (CXCR4) antagonists showed significant anti-metastatic effects by blocking the CXCR4/stromal cell-derived factor-1(SDF-1) axis in pancreatic cancer and breast cancer. Here, we proposed to achieve migration chain-treatment for metastatic tumors by introducing a cell adhesion molecules CD44 inhibitor (Star miR-34a) to deprive of cell migration capability on the basis of CXCR4 antagonism (cyclam monomer , CM). Dextrin modified 1.8 k PEI with CM-end was prepared to deliver therapeutic miR-34a (named DPC/miR-34a) for efficient anti-metastasis by downregulating adhesion protein CD44 and targeting the CXCR4/SDF-1 axis. Additionally, reduced expression of the anti-apoptotic protein Bcl2 caused by miR-34a could enhance the anti-tumor efficacy of DPC/miR-34a nanoplex administration. Compared with inhibition of the CXCR4/SDF-1 axis or CD44 expression, the multidimensional therapy (DPC/miR-34a) exhibited considerable suppression of cancer cell invasion as assessed by an in vitro cell invasion assay and in vivo anti-metastasis model. Moreover, DPC/miR-34a demonstrated a superior antitumor and anti-metastatic efficacy both in lung metastatic model and orthotopic MDA-MB-231 tumor models, thus providing an efficient approach for combating metastatic tumors.
研究领域:
肿瘤学
·
分子生物学
·
药学
·
癌症治疗
✓ 已验证
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）