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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2023 ·Vol. 24 ·期 20 ·15403 · IF 5.6

Berberine-Encapsulated Poly(lactic-co-glycolic acid)–Hydroxyapatite (PLGA/HA) Microspheres Synergistically Promote Bone Regeneration with DOPA-IGF-1 via the IGF-1R/PI3K/AKT/mTOR Pathway

Li Chen,Meng Tian,Jing Yang,Zhenxu Wu

Polymer microspheres have recently shown outstanding potential for bone tissue engineering due to their large specific surface area, good porosity, injectable property, good biocompatibility, and biodegradability. Their good load-release function and surface modifiability make them useful as a carrier of drugs or growth factors for the repair of bone defects in irregularly injured or complex microenvironments, such as skull defects. In this study, berberine (BBR)-encapsulated poly(lactic-co-glycolic acid) (PLGA)/hydroxyapatite (HA) microspheres were fabricated using electrified liquid jets and a phase-separation technique, followed by modification with the 3,4-hydroxyphenalyalanine-containing recombinant insulin-like growth–factor-1 (DOPA-IGF-1). Both the BBR and the IGF-1 exhibited sustained release from the IGF-1@PLGA/HA-BBR microspheres, and the composite microspheres exhibited good biocompatibility. The results of the alkaline phosphatase (ALP) activity assays showed that the BBR and IGF-1 in the composite microspheres synergistically promoted the osteogenic differentiation of MC3T3-E1 cells. Furthermore, it was confirmed that immobilized IGF-1 enhances the mRNA expression of an osteogenic-related extracellular matrix and that BBR accelerates the mRNA expression of IGF-1-mediated osteogenic differentiation and cell mineralization. Further cellular studies demonstrate that IGF-1 could further synergistically activate the IGF-1R/PI3K/AKT/mTOR pathway using BBR, thereby enhancing IGF-1-mediated osteogenesis. Rat calvarial defect repair experiments show that IGF-1@PLGA/HA-BBR microspheres can effectively promote the complete bony connection required to cover the defect site and enhance bone defect repair. These findings suggest that IGF-1@PLGA/HA-BBR composite microspheres show a great potential for bone regeneration.Keywords:polymer microspheres;berberine (BBR);IGF-1;bone regeneration;osteogenic differentiation

CAS / MDL: 141433-60-5
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

Coating TiO2 with MIL-101(Fe) to decarboxylate D-Glu and D-MeAsp of microcystin-LR from HA-rich water: Diminishing the inhibitory effect of humic acids

Yarui Wang,Chengzhuo Yu,Sen Wang,Jin Xu,Fanglan Geng,Silong Wang,Jitao Lv,Lixia Zhao,Yawei Wang

Humic acids (HA) released during algal bloom poses a key challenge for efficient photocatalytic degradation of Microcystin-LR (MC-LR) due to their scavenging function on active species. Herein, MIL-101(Fe)/TiO 2 -P25 (M/P) was constructed to diminish the inhibitory effect of HA on the photocatalytic degradation of MC-LR. Results showed that MC-LR could be efficiently removed assigning to the photogenerated holes (h + ) and superoxide radical (O 2 •− ) oxidation under visible light irradiation, where the carboxy groups of D -glutamic acid (Glu) and methyl- D -aspartic acid (MeAsp), and Adda side chain related to MC-LR biotoxicity were selectively destroyed to achieve MC-LR detoxication. More importantly, HA exerted non-inhibitory effect on MC-LR removal by M/P. The counteracting mechanisms were studied. Firstly, the location of TiO 2 in the pore structure of MIL-101(Fe) could occupy the adsorption sites of HA, and decrease the HA adsorption on M/P. Furthermore, XPS analyses suggested the coordination of unsaturated Fe metal sites on the surface of M/P hybrids complexed with –OH and –COOH of HA, which could accelerate the electron transfer and reduce hole consumption. Thus, the inhibitory effect of HA was alleviated during photocatalytic MC-LR treatment. This work offers a possible way to remove MC-LR in an abundant HA matrix water system efficiently.

CAS / MDL: 68-12-2 98-00-0
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JOURNAL OF MEMBRANE SCIENCE · 2025 · IF 9

Revealing the internal β-phase PVDF membrane fouling tendency using double layer piezoelectrics

Qian Wang,Juan Li,Qiuyueming Zhou,Ting He,Zhaoliang Cui,Young Moo Lee,Weihong Xing

Dissolved organic matter (DOM) is recognized as a crucial factor contributing to the irreversible fouling of ultrafiltration membranes. Quartz crystal microbalance with dissipation (QCM-D) offers insights into the kinetics of fouling layer formation and its structure in-situ on a model membrane. However, a clear correlation between the membrane fouling process and the adsorption-desorption results obtained from QCM-D has yet to be established. In this study, piezoelectric β-phase PVDF membranes were prepared, and their fouling behavior in response to three model compounds (humic acid (HA), dextran (DEX), bovine serum albumin (BSA), and their mixed solutions was examined. It was firstly proposed that the spin-coated model PVDF membrane surface exhibited a typical β-phase structure, characterized by regular undulations resulting from strong stretching effects. A novel double layer piezoelectric sensor, consisting of a β-phase layer over a piezoelectric quartz substrate, was designed for QCM-D analysis to assess the mass and stiffness variations of the absorbed DOM layer. The fouling tendency followed the order of BSA > Mixture > DEX > HA, with the foulant monomeric units having a similar molecular mass of around tens of kDa. Irreversible fouling resistance in series model as well as frequency drop in QCM-D were listed as indicators of irreversible fouling caused by foulant-membrane interaction, which realized a well-defined match for the first time.

CAS / MDL: 127-19-5 674282-83-8
研究领域: 膜科学 · 环境工程 · 材料科学 · 分析化学
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ADVANCED FUNCTIONAL MATERIALS · 2020 ·Vol. 30 ·期 49 ·2002239 · IF 16.836

Establishment of Facile Nanomedicine Construction Methodology to Comprehensively Overcome Hurdles across Tumor-Specific Nano-Delivery

Wuyang Yu,Qian Cheng,Jingjie Ye,Mingkang Zhang,Cheng Zhang,Fan Gao,Xinglan Ding,Jun Feng,Xian-Zheng Zhang

To advance clinical translation of antitumor nanomedicines, the development of a universally applicable, facile, and safe methodology for nanomedicine construction to overcome major hurdles across tumor-specific nano-delivery in an all-in-one manner would be highly desirable. This study puts forward a HAylation strategy based on positively charged nanocore (NC + ) and hyaluronic acid (HA) that is naturally present in the human body. HAylation leads to prolonged blood duration and active tumor targeting. It is demonstrated that HAylation facilitates not only selective uptake of nanomedicines by tumor cells but also deep tumor infiltration via the special transcytosis pathway. This characteristic is ascribed to the site-specific exposure of NC + in tumor cells due to fast HA degradation exclusively in response to HAase and an acidic pH in the lysosome after tumor accumulation. HAylation enables the free construction of a NC + nano-core with versatile functions. Here, a NC + core is fabricated by directly assembling a photodynamic therapy (PDT) agent and an inhibitor of the DNA base excision repair (BER) pathway. The inhibition of BER-mediated DNA repair has proven powerful to amplify antitumor efficacy since DNA damage is one major cell-killing mechanism for many anticancer therapeutics. HAylation holds promise for the simplification of the industrial production of nanomedicines and arms nanomedicines to thoroughly overcome fundamental nano-delivery hurdles.

研究领域: 纳米医学 · 癌症治疗 · 药物递送系统 · 分子生物学
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International Journal of Nanomedicine · 2018 · IF 4.37

Construction and application of a liver cancer-targeting drug delivery system based on core–shell gold nanocages

Mengfei Ji,Xiaojing Qiu,Lin Hou,Shengnan Huang,Yuanmin Li,Yang Liu,Shaofeng Duan,Yurong Hu

Background In order to achieve drug targeting and controlled release, we have successfully developed a novel drug release system DOX/AuNCs-PM-HA with gold nanocages (AuNCs) as photothermal cores, thermally responsive copolymer P(NIPAM-co-Am) (PM) as the near-infrared (NIR) stimuli gatekeeper and hyaluronic acid as a targeting ligand as well as a capping agent. Methods Cell uptake and cell viability were investigated. In vivo photoacoustic tomography imaging in H22 tumor bearing mice was analyzed for the tumor targeting effect of the nanocomplexes. Antitumor efficacy and the tissue distribution in vivo were investigated. Results In vitro results demonstrated that the DOX/AuNCs-PM-HA had significant anticancer activity against SMMC-7721 cells under NIR irradiation. Furthermore, in vivo photoacoustic tomography imaging of the nanocomplexes in H22 tumor bearing mice could indicate effective tumor targeting. Our studies on antitumor efficacy and the tissue distribution in vivo showed that many DOX/AuNCs-PM-HA nanocomplexes could efficiently accumulate at the tumor site so that they could inhibit the tumor growth effectively with limited side effects. The in vitro and in vivo results confirmed that the tumor-targeting and controlled-release drug system DOX/AuNCs-PM-HA with the combination of chemotherapy and photothermal therapy showed strong anti-tumor effect and would have great potential for future cancer therapy. Conclusion This tumor targeting DOX/AuNCs-PM-HA nanocomplex responded not only to the external stimuli of NIR, but also the internal stimuli of hyaluronidase, providing the potential for pinpointed and multi-stimuli responsive intracellular drug release.

研究领域: 纳米技术 · 药学 · 肿瘤学 · 生物医学工程 · 材料科学
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JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY · 2016 · IF 2.267

Effect of Mineralized Layer Topographies on Stem Cell Behavior in Microsphere Scaffold

Jie Hou,Huichang Gao,Yingjun Wang,Delin Cheng,Xiaodong Cao

Modifying substrates through mineralization is a popular way to improve the osteogenic performance. Screening of the best mineralization characteristics on specific substrates for stem cells is meaningful but not fully studied. In this paper, poly(lactic-co-glycolic acid)/hydroxyapatite (PLGA/HA, PH) microsphere scaffolds with superficial pores were fabricated by a low-temperature fusion method. After the mineralization in the 5× stimulated body fluid (SBF) for 0, 7, 12 and 24 h, four mineralized scaffolds (MPH-0, MPH-7, MPH-12 and MPH-24) with different apatite topographies were obtained. It was found that the surface of MPH-7 was evenly decorated with abundant micro-pores, MPH-12 with dense and plain apatite layer, and MPH-24 with small spherical bumps. The responses of mouse bone mesenchymal stem cells (mBMSCs) to the four scaffolds were further studied. The results showed that MPH-7 and MPH-24 had more obvious effects on mBMSCs attachment, proliferation and differentiation than MPH-0 and MPH-12. This work indicated that to obtain the maximum improvement, the mineralization characteristics had to be carefully chosen. This was noteworthy in the chemical modification of surfaces to form the functionalized scaffolds for bone repair.

CAS / MDL: 90-80-2 9002-89-5
研究领域: 生物材料 · 组织工程 · 干细胞研究 · 材料科学 · 生物医学工程
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CHEMOSPHERE · 2022 · IF 8.943

UV/Fe(II) synergistically activated S(IV) per-treatment on HA-enhanced Ca2+ scaling in NF filtration: Fouling mitigation, mechanisms and correlation analysis of membrane resistance in different filtration stage

Wenkai Liu,Bin Liu,Xin Li

The aim of this study was to investigate the feasibility and fouling mitigation mechanisms of UV/Fe(II) synergistically activated sulfite (S(IV)) (UFS) pretreatment to alleviate membrane fouling caused by HA-enhanced Ca 2+ scaling. After UFS treatment, hydrophobic substances and carboxyl groups structure were destroyed by the in-situ-generated SO•–4, resulted in a significant reduction of hydrophobic substances ratio and carboxyl group concentration. Due to the formation of more electropositive in-situ-generated Fe(III), the complexation between Ca 2+ and carboxyl groups was weakened so that the bulk crystallization size on the membrane surface was greatly reduced. The filter cake enhanced osmotic pressure effect (CEOP) and concentration polarization effect were hence alleviated, as well as the surface roughness . At the microcosmic perspective, as the energy barrier between the membrane and foulants was increased significantly after pretreatment, the anti -foulants adsorption ability of the membrane was enhanced. Correlation analysis showed that the carboxyl concentration and density, HPO ratio, larger particle size (>100 nm) ratio, the Ca 2+ concentration in the scaling layer and energy barrier all had a good correlation with the membrane resistance. This research not only provides an advanced oxidation technology that can effectively alleviate the synergistically-fouling effect of HA and Ca 2+ of nanofiltration process, but also proposes a guidance for the UV/Fe(II) synergistically activated sulfite.

CAS / MDL: 67-56-1 75-65-0
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International Journal of Extreme Manufacturing · 2024 · IF 16.1

Efficient concentration of trace analyte with ordered hotspot construction for a robust and sensitive SERS platform

Youdi Hu,Yanlei Hu,Zhenyu Wang,Jiale Yong,Wei Xiong,Dong Wu,Shixiang Xu

Surface enhanced Raman scattering (SERS) enabled trace molecules detection has important application prospects. By structuring/modifying the surface of SERS substrate, molecules in highly-diluted solution can be concentrated into localized active area for highly sensitive detection. However, subject to the difficulty of fabrication process, it remains challenging to balance hot-spots construction and concentration capacity to molecules simultaneously. Therefore, preparing SERS substrate with dense ordered hot-spots and efficient concentration capacity is of great significance for highly sensitive detection. Herein, we propose the Ag and fluoroalkyl modified hierarchical armour substrate (Ag/F-HA), which has a double-layer stacking design to combine analyte concentration with hotspot construction. The micro armour structure fabricated by femtosecond-laser processing to serve as a superhydrophobic and low-adhesive surface to concentrate molecules, while anodic aluminum oxide (AAO) template creates nanopillars array serving as dense and ordered hot spots. Under the synergy action of hot-spots and molecule concentration, Ag/F-HA achieves the detection limit down to 10−7 M of Doxorubicin (DOX) molecules with a relative standard deviation (RSD) of 7.69%. Additionally, Ag/F-HA exhibits the excellent robustness to resist external disturbance such as liquid splash or abrasion. Based on our strategy, the SERS substrates with directional analyte concentration are further explored by patterning microcone array with a defect. This work opens a way to the realistic implementation of SERS in diverse scenarios.

CAS / MDL: 101947-16-4
研究领域: 分析化学 · 材料科学 · 纳米技术 · 生物医学工程
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MATERIALS & DESIGN · 2024 · IF 7.6

Physically crosslinked poly(vinyl alcohol)-based hydrogels for cartilage tissue engineering

Changxin Xiang,Zijian Guo,Qing Zhang,Zehua Wang,Xiaona Li,Weiyi Chen,Xiaochun Wei,Pengcui Li,Chuan Xiang

Due to the limited self-healing ability of cartilage, cartilage defect repair remains a challenge in clinical treatment. Therefore, there is a need to provide patients with a promising cartilage defect repair strategy. In this study, we have reported an icariin-loaded PVA based biocompatible hydrogel scaffold for cartilage defect repair. The PTGH+Icariin hydrogel was prepared by a simple physical cross-linking method and consisted of polyvinyl alcohol (PVA), tannic acid (TA), gelatin (Gel), hyaluronic acid (HA) and icariin. Inspired by the natural cartilage matrix compositions, the Gel and HA were used to improve the bioactivity and biocompatibility of hydrogel. Furthermore, icariin was introduced to further enhance the hydrogel’s ability for cartilage regeneration. The results showed that PTGH+icariin hydrogel exhibited porous microstructures and tough mechanical properties. In vitro cell experiments confirmed PTGH+Icariin hydrogels could promote chondrocytes proliferation, chondrocytes spreading and chondrocytes migration. Meanwhile, the PTGH+Icariin hydrogel demonstrated the ability to promote the cartilage regeneration in a rat cartilage defect model. In particular, the implantation of PTGH+Icariin hydrogel could facilitate the restoration of motor function in rats. This study will provide a potential approach for the treatment of cartilage defects.

CAS / MDL: 9000-70-8 9002-89-5
研究领域: 组织工程 · 生物材料 · 生物医学工程 · 再生医学
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ACS Applied Nano Materials · 2024 · IF 5.3

Glutathione-Responsive Nanoplatforms Based on Coordination between Fe3+ and Apigenin for Synergistic Chemo/Chemodynamic Therapy

Zhi-Hang He,Han-Xiao Tang,Yan-Zheng Pan,Min Cen,Zhi-Juan Zhang

The oxygen consumption during chemodynamic therapy (CDT) can lead to severe cellular hypoxia, resulting in an increase in the hypoxia inducible factor-1α (HIF-1α) level, which hinders the effectiveness of CDT and induces tumor metastasis. Here, we propose a strategy of synergistic therapy between CDT and the HIF-1α inhibitor to avoid the limitations of CDT and reduce the risk of metastasis. Herein, based on the coordination between Fe3+ and apigenin (API, HIF-1α inhibitor), we constructed a hyaluronic acid (HA)-modified API-Fe nanoparticles (AF@HA NPs) for synergetic chemotherapy and glutathione (GSH)-activated self-enhancing CDT. AF@HA NPs have high drug loading capacity, stability, and biocompatibility. Furthermore, the overexpressed GSH in cancer cells can reduce Fe3+ to Fe2+, weakened the coordination between API and Fe, and promoted the release of API for chemotherapy. Fe2+ could react with endogenous H2O2 to generate hydroxyl groups for CDT. In addition, the released API could inhibit the expression of HIF-1α and increase the sensitivity of cells to reactive oxygen species (ROS), thereby achieving a synergistic effect between self-enhancing CDT and chemotherapy. The results of in vitro and in vivo experiments indicated that AF@HA NPs could effectively inhibit tumor growth and suppress the lung metastasis of tumor cells.

CAS / MDL: 10025-77-1
研究领域: 纳米技术 · 癌症治疗 · 药理学 · 生物医学工程 · 分子生物学
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RSC Advances · 2018 ·Vol. 8 ·期 48 ·27191-27200 · IF 2.936

Recombinant human BMP-7 grafted poly(lactide-co-glycolide)/hydroxyapatite scaffolds via polydopamine for enhanced calvarial repair

Qinli Xu,Ye Li,Yuhang Zhu,Kunchi Zhao,Rui Gu,Qingsan Zhu

Poly(lactic-co-glycolic acid) (PLGA) and hydroxyapatite (HA) are considered potential osteoinductive materials because of their biodegradability and mineralization features. However, the hydrophobicity of scaffold surfaces is less supportive of cell attachment and proliferation because of poor wettability. The mode of binding of growth factors to the scaffold also affects cell differentiation into osteoblasts. The half-life of a growth factor in vivo can be increased by binding the factor to the scaffold surface. In this work, we prepared a porous PLGA/HA scaffold grafted with recombinant human bone morphogenic protein-7 (rhBMP-7) attached via polydopamine (pDA) for bone repair. The pDA coated PLGA/HA (pDA-PLGA/HA) scaffolds were characterized by energy dispersive X-ray analysis and Fourier-transform infrared spectroscopy. The microstructure and porosity of PLGA/HA scaffolds were analyzed by scanning electron microscopy and micro-computed tomography. The release profile of rhBMP-7 grafted onto the pDA-PLGA/HA (pDA-PLGA/HA/BMP-7) scaffolds was examined for 21 days. The attachment efficiency, cell proliferation rate, alkaline phosphatase activity, calcium deposition, and osteoblast-related gene expression of bone marrow-derived stem cells to PLGA/HA, pDA-PLGA/HA, and pDA-PLGA/HA/BMP-7 scaffolds were evaluated. To assess the ability of bone repair in vivo, scaffolds were implanted into critical-sized calvarial defects created in mice, and the in vivo tissue-engineered bone was monitored by micro-computed tomography and histology. In vivo experiments revealed rapid healing of the defects treated with the pDA-PLGA/HA/BMP-7 scaffolds compared with pDA-PLGA/HA and PLGA/HA scaffolds at week 8 post-surgery. These results collectively demonstrate that the rhBMP-7-immobilized PLGA/HA scaffold via pDA is a promising candidate for calvarial repair.

研究领域: 生物医学工程 · 组织工程 · 材料科学 · 骨科
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ADVANCED FUNCTIONAL MATERIALS · 2025 · IF 19

Armoring Vascular Implant by Glycocalyx-Mimetic Coating with Clustered Morphology and Hydrophilic Lubrication

Fanjun Zhang,Yao Xiong,Yage Hu,Jingze Liu,Yuan Wei,Li Yang,Rifang Luo,Yunbing Wang

The endothelial glycocalyx is a natural protective layer for blood vessels. Efficient construction of a reliable glycocalyx-mimetic coating on a vascular implant possesses great potential but remains a challenge. Herein, a novel glycocalyx-mimetic coating featuring the clustered morphology and hydrophilic lubrication is developed via the layer-by-layer self-assembly of polyethyleneimine (PEI) and phosphorylcholine-modified hyaluronic acid (HA-PC). The zwitterionic PC groups in HA-PC exhibited an anti-polyelectrolyte effect to induce the molecular folding and aggregation of HA in solution and enhance its binding capacity to PEI, resulting in an endothelial glycocalyx-mimetic clustered morphology. Besides, zwitterions, rather than hydrophobic groups, can achieve hydrophilic lubrication properties through spatial synergy with HA while inducing the molecular folding of HA, ultimately constructing a glycocalyx-mimetic coating. Such a coating can function well as armor to vascular stent, by virtue of excellent anti-coagulation, anti-inflammation, and endothelial promotion properties in vivo and in vitro. The findings not only provide new insights into the interactions between PC-modified polyelectrolytes but also render a promising glycocalyx-mimetic coating to armor vascular implants.

CAS / MDL: 9041-08-1
研究领域: 生物材料 · 组织工程 · 生物医学工程 · 血管生物学
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