ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2023
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IF 6.8
Rui Yan,Jie Ding,Qianlei Yang,Xiaoyun Zhang,Junyu Han,Tingxu Jin,Shudi Shi,Xirui Wang,Yu Zheng,Heran Li,Hengdong Zhang,Yan An
Skeletal system toxicity due to lead exposure has attracted extensive attention in recent years, but few studies focus on the skeletal toxicity of lead in the early life stages of zebrafish. The endocrine system, especially the GH/IGF-1 axis, plays an important role in bone development and bone health of zebrafish in the early life. In the present study, we investigated whether lead acetate (PbAc) affected the GH/IGF-1 axis, thereby causing skeletal toxicity in zebrafish embryos. Zebrafish embryos were exposed to lead PbAc between 2 and 120 h post fertilization (hpf). At 120 hpf, we measured developmental indices, such as survival, deformity, heart rate, and body length, and assessed skeletal development by Alcian Blue and Alizarin Red staining and the expression levels of bone-related genes. The levels of GH and IGF-1 and the expression levels of GH/IGF-1 axis-related genes were also detected. Our data showed that the LC50 of PbAc for 120 h was 41 mg/L. Compared with the control group (0 mg/L PbAc), after PbAc exposure, the deformity rate increased, the heart rate decreased, and the body length was shortened at various time periods, in the 20-mg/L group at 120 hpf, the deformity rate increased by 50 fold, the heart rate decreased by 34%, and the body length shortened by 17%. PbAc altered cartilage structures and exacerbated bone loss in zebrafish embryos; in addition, PbAc exposure down-regulated the expression of chondrocyte ( sox9a , sox9b ), osteoblast ( bmp2 , runx2 ) and bone mineralization-related genes ( sparc , bglap ), and up-regulated the expression of osteoclast marker genes ( rankl , mcsf ). The GH level increased and the IGF-1 level declined significantly. The GH/IGF-1 axis related genes ( ghra , ghrb , igf1ra , igf1rb , igf2r , igfbp2a , igfbp3 , igfbp5b ) were all decreased. These results suggested that PbAc inhibited the differentiation and maturation of osteoblasts and cartilage matrix, promoted the formation of osteoclasts, and ultimately induced cartilage defects and bone loss by disrupting the GH/IGF-1 axis.
研究领域:
毒理学
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内分泌学
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发育生物学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Botao Liu,Mingming Hao,Jianping Chen,Xiaodong Hu,Jiaqi Zhong,Yujiong Chen,Han Yu,Hangbin Weng,Zhewei Zhang,Tianyu Du,Zhaoxiang Peng
Critical-sized bone defects pose notable therapeutic challenges and often require extensive bone grafts for effective intervention, leading to a substantial medical burden. The scarcity of autologous bone and the complex architecture of trabecular bone necessitate the development of cost-effective biomimetic graft materials. In this study, we developed a MgO nanoparticle-incorporated hydrogel scaffold (P-G-C-MgO2) using a freeze-induced phase separation approach. The scaffold achieved a porous structure with 56.48 ± 7.062 % porosity and an average pore size of 565.7 ± 53.62 μm, closely mimicking natural trabecular bone. It demonstrated exceptional mechanical stability during degradation and consistently released bioactive components, including Mg 2+ , type I collagen, and gelatin. These features facilitated early cell recruitment and osteogenic differentiation. In a distal femoral bone defect model, P-G-C-MgO2 exhibited excellent osseointegration and significantly enhanced new bone regeneration. This biomimetic design offers a promising solution for bone defect repair. Moreover, it established a novel phase-separation-based strategy for fabricating porous hydrogel scaffolds.
研究领域:
生物材料学
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组织工程
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再生医学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Shi Liu,Xinlin Jia,Jina Hao,Dapeng Zhang,Shengchao Yang,Bin Dai,Yuanqing Mao,Yongsheng Li
Cell senescence or apoptosis contributes to self-failure and functional loss in specialized cells, leading to incapacity of the body to repair specific damages. Senescent bone marrow mesenchymal stem cells (BMSCs) lose their proliferative abilities and secrete senescence-associated secretory phenotype (SASP), hindering their participation in bone defect repair. Hence, the effective suppression of cell senescence is crucial to restore the self-repair capacity of body to treat bone defects. Since the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is associated with SASP secretion, herein, we propose a new strategy to inhibit this pathway to suppress SASP secretion and enhance osteoblast activity based on a novel hierarchically biomimetic nanostructural electrospun scaffold with JAK inhibitors (JAKi, Ruxolitinib) loaded. As validated by in vitro and in vivo experiments, the JAKi loaded scaffold reduces SASP expression effectively and alleviates senescent cell burden, creating a pro-regeneration microenvironment that enhances osteoblast function and mineralization activity as well as rejuvenating the bone repair capacity. These findings offer insights into the regulatory role of cellular senescence in bone aging and provide a new and effective strategy to treat age-related bone defects by delivery of JAKi to locally aging bone defect sites. This article is protected by copyright. All rights reserved
研究领域:
生物材料学
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组织工程学
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再生医学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Wei Xiong,Yuxiang Zhou,Xiaolin Shi,Chaoyi Liang,Wenfang Deng,Lingmei Yuan,Guowen Qian,Cijun Shuai,Zhikui Zeng
The treatment of infective bone defects remains a considerable challenge for orthopedic surgeons, primarily due to the complexities of infection control and the unsatisfactory healing of bone tissue. To solve this challenge, we have designed core/shell nanoparticles to loaded with antibacterial and osteogenic agents. Specifically, magnetocaloric CoFe2O4 (CF) nanoparticles loaded with naringin (NG) and coated with mesoporous silica (MS) were developed to construct NG-CF@MS nanoparticles. Subsequently, levofloxacin (LEV) was loaded into the MS coating, yielding NG-CF@MS-LEV nanoparticles capable of dual drug delivery. These nanoparticles were then incorporated into poly l-lactide (PLLA) powder to fabricate magnetically responsive scaffolds, which demonstrated enhanced osteogenesis and antibacterial activity under alternating magnetic field (AMF) conditions. Drug release studies showed a significant increase in NG and LEV release efficiency in the AMF setting, with a 337% increase in NG release and a 196% increase in LEV compared to non-AMF conditions. In vitro experiments further demonstrated that NG-CF@MS-LEV/PLLA scaffolds exhibited excellent osteogenic and antibacterial properties. Under the intervention of the AMF, the scaffolds displayed antibacterial rates of 98.67% and 99.38% against Escherichia coli and Staphylococcus aureus, respectively. Moreover, the scaffolds significantly promoted osteogenic differentiation and mineralization of mouse bone marrow mesenchymal stromal cells (mBMSCs), highlighting their potential as a promising therapeutic approach for repair of infected bone defects.
研究领域:
生物材料学
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骨科医学
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药剂学
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产品关联
DOI
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2024
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IF 4.9
Xiaona Zhang,Yubin Tang,Shulin Liu,Ying Zhang
Multiple myeloma (MM) is an incurable plasma cell hematologic tumor in which bone pain is a typical symptom. The current main treatment methods not only easily cause multidrug resistance but also cause bacterial infections. Therefore, improving multidrug resistance and bacterial infection during MM therapy and repairing bone defects caused by bone pain are necessary. In this work, we propose a drug delivery platform of lithium-doped bioactive glass microspheres (7Li-MBGs) with a mesoporous structure (2–5 nm) and a high specific surface area (636 m 2 /g) to achieve these functions. Interestingly, lithium ions are network modifier doped into the silicon-oxygen network. This in turn affects the dissolution and release behavior of silicon ions in the MBGs network. Thus, the bioactive response as well as drug release of the MBGs were enhanced. During this process, hydroxyapatite easily forms on the surface, which has a therapeutic effect on bone defects caused by MM. The drug (mitoxantrone hydrochloride, MTO) release mechanism is diffusion-driven, suggesting that drug/platform interactions are key determinants of release kinetics and depend on the release medium environment and platform structure. In vitro antibacterial and cytotoxicity experiments proved that the synergistic effect of Li ions and the MTO improved the antibacterial ability of the MBGs (> 98%) and the ability to treat MM. Therefore, the proposed 7Li-MBGs drug delivery platform can effectively release drugs in the long-term, repair bone defects, inhibit bacterial growth and tumor cell activity, and provide new ideas for the treatment of MM.
研究领域:
材料科学
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生物医药
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肿瘤学
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产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2025
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IF 19
Xiaokun Yue,Xueheng Sun,Zilin Li,Tianchang Wang,Weiqing Kong,Shuai Li,Jing Shan,Hao Yang,Weize Kong,Wentao Li,Changru Zhang,Bin Cai,Kerong Dai,Yuxin Zhang,Xin Sun,Jinwu Wang
Bone defects caused by trauma, infection, or tumors pose significant clinical challenges, particularly in large defects with poor healing outcomes. Traditional repair methods often fail to address the complex regenerative microenvironment. This study introduces a novel biomimetic piezoelectric periosteum-bone bilayer implant designed to remodel the osteogenic microenvironment and enhance bone defect repair. The implant comprises an upper electrospun polyvinylidene fluoride-curcumin-loaded magnesium metal–organic framework (PVDF-MOF/Cur, PMC) periosteum scaffold and a lower hydroxyapatite@gelatin methacrylate (HA@GelMA) bone scaffold (PMC+HA@GelMA, PMCG). In the whole PMCG bilayer implant, the upper PMC periosteum scaffold improves the piezoelectric properties of PVDF and enables sustained drug release via Mg-MOF loaded with Cur. Meanwhile, the lower HA@GelMA scaffold facilitates bone marrow mesenchymal stem cells osteogenic differentiation and bone regeneration. Additionally, the upper PMC scaffold further accelerates bone repair by promoting neuronal differentiation, as well as enhancing angiogenesis and regulating macrophage polarization. Transcriptome sequencing reveals that the implant activates key signaling pathways associated with angiogenesis, neurogenesis, inflammation regulation, and osteogenesis, including HIF-1α, PI3K-Akt, JAK-STAT, and TGF-β pathways. Thus, this work highlights the multifunctional capabilities of the biomimetic periosteum-bone bilayer implant to remodify the osteogenic microenvironment to accelerate bone defect repair, which offers a promising platform for advancing tissue repair.
研究领域:
生物材料学
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再生医学
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骨科
✓ 已验证
产品关联
DOI
高影响因子
FASEB JOURNAL
·
2022
·Vol. 36
·期 10
·e22530
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IF 5.834
Chengyu Yang,Yang Liu,Ziyan Wang,Minmin Lin,Chao Liu
Despite the best treatment, approximately 10% of fractures still face undesirable repair and result in delayed unions or non-unions. Dynamic mechanical stimulation promotes bone formation, when applied at the correct time frame, with optimal loading magnitude, frequency, and repetition. Controlled mechanical loading significantly increases osteogenic cells during the matrix deposition phase of bone repair. In the bone defect, the blood vessel network guides the initial bone formation activities. A unique blood vessel subtype (Type H) exists in bone, which expresses high levels of CD31 and endomucin, and functions to couple angiogenesis and osteogenesis. However, how this form of controlled mechanical loading regulates the Type H vessels and promotes bone formation is still not clear. Sphingosine 1-phosphate (S1P) participates in the bone anabolic process and is a key regulator of the blood vessel. Its receptor, sphingosine 1-phosphate receptor 1 (S1Pr1), is a mechanosensitive protein that regulates vascular integrity. Therefore, we hypothesis that controlled anabolic mechanical loading promotes bone repair by acting on Type H vessels. To study the effect of S1Pr1 on loading induced-bone repair, we utilized a stabilized tibial defect model, which allows for the application of anabolic mechanical loading. Mechanical loading upregulated S1Pr1 within the entire defect, with up to 80% expressed in blood vessels, as observed by deep tissue imaging. Additionally, S1Pr1 antagonism by W146 inhibited the anabolic effects of mechanical loading. We showed that mechanical loading or activating S1Pr1 could induce YAP nuclear translocation, a key regulator in the cell's mechanical response, in endothelial cells (ECs) in vitro. Inhibition of S1Pr1 in endothelial cells by siRNA reduced loading-induced YAP nuclear translocation and expressions of angiogenic genes. In vivo, YAP nuclear translocation in Type H vessels was up-regulated after mechanical loading but was inhibited by antagonizing S1Pr1. S1Pr1 agonist, FTY720, increased bone volume and Type H vessel volume, similar to that of mechanical stimulation. In conclusion, controlled anabolic mechanical loading enhanced bone formation mainly through Type H vessels in a S1Pr1-dependent manner.
研究领域:
骨科
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再生医学
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生物力学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2024
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IF 5.8
Runquan Zheng,Ning Zhang,Songbo Mao,Jiawei Li,Xuesong Yan,Guichun Zhang,Yongxian Zhang,Xianhu Yue
Bone defects and congenital bone deficiencies are common clinical conditions. However, conventional non-degradable artificial materials often lead to serious complications, such as severe infections and material displacement. The emergence of tissue engineering and the organoids concept presents a promising approach for the repair of bone defects, facilitating physiological reconstruction while minimizing complications. Nevertheless, previous studies have not developed injectable organoids that incorporates fully mineralized and organic microenvironments to achieve rapid osteogenesis and convenient application in bone regeneration. Therefore, it is imperative to devise an effective strategy to address these challenges. This study first prepared injectable GL scaffolds with varying concentrations and identified the optimal GL concentration for osteogenesis through systematic evaluation of osteogenic efficiency. Subsequently, inorganic salts of native bone (NBIS) and extracellular matrix from the periosteum (pECM) were integrated into the optimal GL scaffold to create an injectable scaffold featuring biomimetic mineralized and organic microenvironments. This scaffold was further utilized for in vitro analysis of osteogenic mechanisms and injected subcutaneously into rabbits for only four weeks to assess its osteogenic efficacy in vivo. The results indicated that the incorporation of NBIS and pECM significantly enhanced osteogenic efficacy by actively regulating ossification and ECM-receptor interaction signaling pathways, as well as upregulating RUNX2, ALP, COL1, and LAMA. This study introduces a promising injectable strategy for rapid osteogenesis using fully mineralized and organic biomimetic organoids.
研究领域:
组织工程
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骨再生
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生物材料
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医学生物技术
✓ 已验证
DOI
PubMed
高影响因子
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