ADVANCED FUNCTIONAL MATERIALS
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2025
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IF 19
Junwu Wang,Yuhao Xia,Zhuowen Hao,Guang Shi,Qi Zhang,Chenglong Wang,Mengyue Zhu,Yilong Huang,Lanhong Guo,Tian Luan,Tonghe Zhu,Honglian Dai,Jingfeng Li
Hyperglycemia and its induced oxidative stress microenvironment present formidable challenges to the repair of diabetic bone defects. Herein, a novel TZGP (α-TCP/ZnO/GM@P2) composite scaffold for diabetic bone defect repair is developed. Characterization results demonstrate that the α-TCP cement scaffold, ZnO nanoparticles, and gelatin microspheres loaded with and protecting P2 (a novel parathyroid hormone-related peptide) achieve complementary advantages. The TZGP scaffold, while meeting the mechanical strength requirements of cancellous bone, compensates for the deficiency of bioactive peptides in inorganic scaffolds. Its biocompatibility is enhanced, and the scaffold is endowed with antibacterial and antioxidant properties. The in vitro and in vivo results reveal that the TZGP scaffold releases active factors P2 and Zn 2+ , promotes cell proliferation and recruitment in a high-glucose microenvironment, reduces cellular reactive oxygen species accumulation, improves DNA injury and mitochondrial homeostasis, and induces osteogenic-angiogenic differentiation. Compared with the conventional α-TCP scaffold, the TZGP scaffold exhibits more excellent biodegradability, accelerates local tissue filling, and promotes bone accumulation and vascular reconstruction in diabetic bone defects. Consequently, the novel design strategy of the TZGP scaffold offers a promising approach to repairing diabetic bone defects.
研究领域:
生物医学工程
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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
高影响因子
Materials Today Bio
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2022
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IF 10.761
Xi He,Wenbin Liu,Yanling Liu,Kai Zhang,Yan Sun,Pengfei Lei,Yihe Hu
Bone nonunion or delayed union, caused by stripping or injuring of periosteum, is the most common sequelae of segmental bone defects. The preservation of periosteum, or the use of periosteal grafts, can significantly improve the integration of bone graft, speeding up the process of bone reconstruction. However, in most cases, periosteum cannot be preserved with bioactivity. Thus, it is pivotal to develop artificial periosteum. In this study, artificial periosteum of PLGA/MgO/Quercetin was prepared by electrospinning. PLGA/MgO/Quercetin membranes were shown to have a highly porous surface and microstructure, as observed by scanning electron microscopy. Along with excellent biocompatibility, PLGA/MgO/Quercetin membranes promoted cell proliferation and migration, as well as osteogenic differentiation of BMSCs (Bone marrow mesenchymal stem cells) in a dose-dependent manner through the activation of Wnt/β-Catenin pathway. The PLGA/MgO/Quercetin membranes, with an appropriate concentration of quercetin (<1 wt%), promoted EPCs (Endothelial progenitor cells) angiogenesis. In a subcutaneous implantation model and rat skull defect model, optimal osteogenesis and angiogenesis function were observed for the PLGA/20 wt% MgO/0.1 wt% Quercetin membrane. In conclusion, PLGA/MgO membranes, with an appropriate concentration of quercetin, show a variety of biological activities and are promising materials for the generation of artificial periosteum.
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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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2024
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IF 6.9
Zhongyuan Zhang,Wenshu Xu,Zhenhua Zhang,Xiaoxue Chen,Hui Jin,Ningning Jiang,Hui Xu
This study was to investigate the potential mechanisms of treatment with metformin (Met) combined with kaempferol (Kae) against postmenopausal osteoporosis. Experiments were conducted in both ovariectomy (OVX)-induced osteoporosis rats and in vitro using RAW264.7 cells, MC3T3-E1 cells, and HUVECs. Results demonstrated the therapeutic effect of Met combined with Kae on osteoporosis. In vivo, Kae alone and in combination with Met treatments enhanced tibial trabecular microstructure, bone mineral density (BMD), and mechanical properties in OVX rats without causing hepatotoxicity and nephrotoxicity. It also reduced bone resorption markers (CTX-1 and TRAP) and increased the bone formation marker (PINP) level in the serum of OVX rats. The expression of bone resorption marker TRAP was reduced, while bone formation markers Runx2 and ALP were enhanced in the bone tissue of OVX rats. Furthermore, Met combined with Kae also promoted the expression of angiogenesis-related markers CD31 and VEGF in OVX rats. In vitro, MC3T3-E1s cells treated with Met combined with Kae showed higher expression of ALP, Runx2, and VEGF. Interestingly, the treatment did not directly promote HUVECs migration and angiogenesis, but enhanced osteoblast-mediated angiogenesis by upregulating VEGF levels. Additionally, Met combined with Kae treatment promoted VEGF secretion in MC3T3-E1, and activated the Notch intracelluar pathway by upregulating HES1 and HEY1 in HUVECs. Meantime, their stimulation on CD31 expression were inhibited by DAPT, a Notch signaling inhibitor. Overall, this study demonstrates the positive effects of Met combined with Kae on osteoporotic rats by promoting osteogenesis-angiogenesis coupling, suggesting their potential application in postmenopausal osteoporosis.
研究领域:
药理学
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骨科
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
ADVANCED MATERIALS
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2023
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IF 29.4
Haitao Guan,Wei Wang,Zichao Jiang,Boyu Zhang,Zhipeng Ye,Judun Zheng,Wei Chen,Yuhui Liao,Yingze Zhang
Osteoporosis, characterized by an imbalance in bone homeostasis, is a global health concern. Bone defects are difficult to heal in patients with osteoporosis. Classical drug treatments for osteoporotic bone defects have unsatisfactory efficacy owing to side effects and imprecise delivery problems. In this study, a magnetic aggregation-induced bone-targeting poly(lactic-co-glycolic acid, PLGA)-based nanocarrier (ZOL-PLGA@Yoda1/SPIO) is synthesized to realize dual-targeted delivery and precise Piezo1-activated therapy for osteoporotic bone defects. Piezo1 is an important mechanotransducer that plays a key role in regulating bone homeostasis. To achieve dual-targeting properties, ZOL-PLGA@Yoda1/SPIO is fabricated using zoledronate (ZOL)-decorated PLGA, superparamagnetic iron oxide (SPIO), and Piezo1-activated molecule Yoda1 via the emulsion solvent diffusion method. Bone-targeting molecular mediation and magnetic aggregation-induced properties can jointly and effectively achieve precise delivery to localized bone defects. Moreover, Yoda1 loading enables targeted and efficient mimicking of mechanical signals and activation of Piezo1. Experiments in vivo and in vitro demonstrate that ZOL-PLGA@Yoda1/SPIO can activate Piezo1 in bone defect areas of osteoporotic mice, improve osteogenesis through YAP/β-catenin signaling axis, promote a well-coordinated osteogenesis–angiogenesis coupling, and significantly accelerate bone reconstruction within the defects without noticeable side effects. Overall, this novel dual-targeting nanocarrier provides a potentially effective strategy for the clinical treatment of osteoporotic bone defects.
研究领域:
生物医学工程
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纳米技术
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骨生物学
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力学生物学
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药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
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2023
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IF 17.1
Weijing Feng,Yintong Teng,Qingping Zhong,Yangmei Zhang,Jianwu Zhang,Peng Zhao,Guoqing Chen,Chunming Wang,Xing-Jie Liang,Caiwen Ou
As the prevalence of vascular calcification (VC), a strong contributor to cardiovascular morbidity and mortality, continues to increase, the need for pharmacologic therapies becomes urgent. Sodium thiosulfate (STS) is a clinically approved drug for therapy against VC; however, its efficacy is hampered by poor bioavailability and severe adverse effects. Plant-derived extracellular vesicles have provided options for VC treatment since they can be used as biomimetic drug carriers with higher biosafety and targeting abilities than artificial carriers. Inspired by natural grapefruit-derived extracellular vesicles (EVs), we fabricated a biomimetic nanocarrier comprising EVs loaded with STS and further modified with hydroxyapatite crystal binding peptide (ESTP) for VC-targeted delivery of STS. In vitro, the ESTP nanodrug exhibited excellent cellular uptake capacity by calcified vascular smooth muscle cells (VSMCs) and subsequently inhibited VSMCs calcification. In the VC mice model, the ESTP nanodrug showed preferentially the highest accumulation in the calcified arteries compared to other treatment groups. Mechanistically, the ESTP nanodrug significantly prevented VC via driving M2 macrophage polarization, reducing inflammation, and suppressing bone-vascular axis as demonstrated by inhibiting osteogenic phenotype trans-differentiation of VSMCs while enhancing bone quality. In addition, the ESTP nanodrug did not induce hemolysis or cause any damage to other organs. These results suggest that the ESTP nanodrug can prove to be a promising agent against VC without the concern of systemic toxicity.
研究领域:
药理学
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纳米技术
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心血管疾病
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生物材料
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BONE
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2022
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IF 4.626
Abdusami Abdurahman,Xinle Li,Jie Li,Daquan Liu,Lidong Zhai,Xuetong Wang,Yifan Zhang,Yao Meng,Hiroki Yokota,Ping Zhang
Bone vasculature influences osteogenesis and haematopoiesis in the bone microenviroment. Mechanical loading has been shown to stimulate the formation of osteogenesis-related type H vessels in an ovariectomy (OVX)-induced osteoporosis mouse model. To determine the loading-driven mechanism of angiogenesis and the formation of type H vessels in bone, we evaluated the roles of PI3K/Akt signaling and erythropoiesis in the bone marrow . The daily application of mechanical loading (1 N at 5 Hz for 6 min/day) for 2 weeks on OVX mice inhibited osteoclast activity , associated with an increase in the number of osteoblasts and trabecular volume ratio. Mechanical loading enhanced bone vasculature and vessel formation, as well as PI3K/Akt phosphorylation and erythropoiesis in the bone marrow. Notably, LY294002 , an inhibitor of PI3K signaling, blocked the tube formation by endothelial progenitor cells , as well as their migration and wound healing. The conditioned medium, derived from erythroblasts , also promoted the function of HUVECs with elevated levels of VEGF, CD31 , and Emcn. Collectively, this study demonstrates that mechanical loading prevents osteoporotic bone loss by promoting angiogenesis and type H vessel formation. This load-driven preventing effect is in part mediated by PI3K/Akt signaling and erythropoiesis in the bone marrow.
研究领域:
骨骼生物学
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细胞信号传导
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血管生成
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骨质疏松研究
✓ 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）