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ACS Applied Bio Materials · 2024 · IF 4.6

Microsphere-Composite Hydrogel for Recruiting Stem Cells and Promoting Osteogenic Differentiation

Juan Zhou,Yanling Zhao,Yan Ling,Peng Zhao,Hui Gao,Yang Yang,Jinghua Chen

By recruiting stem cells into scaffolds and differentiating them into osteoblasts, stem cells can be mobilized to directly repair bone defects, which avoids a series of disadvantages of exogenous stem cell implantation. In this study, a microsphere-composite hydrogel for the recruitment and osteogenic differentiation of stem cells was constructed. Methacrylic anhydride modified gelatin (GelMA) and heparin (HepMA), as well as nanohydroxyapatite (nHAP), were used to prepare microspheres followed by adsorbing platelet-derived growth factor BB (PDGF-BB) whose loading efficiency was 53.7 ± 2.2%. Then the microspheres were compounded to the GelMA hydrogel encapsulated with simvastatin (SIM) to obtain microsphere-composite hydrogel GHnH-P@GS. GHnH-P@GS hydrogel could slowly release SIM and PDGF-BB, and the extents of release within 7 days were 44.1 ± 2.0% and 32.8 ± 1.1%. The synergistic effect of small molecule drugs and growth factors not only induced the recruitment of rabbit bone marrow-derived mesenchymal stem cells, but also promoted the osteogenic differentiation of stem cells, which was confirmed by experiments of cell migration, alkaline phosphatase, and alizarin red staining. Collectively, the microsphere-composite hydrogel GHnH-P@GS has a certain reference significance for the design of scaffolds for alveolar bone repair and regeneration.

CAS / MDL: 79902-63-9
研究领域: 组织工程 · 再生医学 · 生物医学材料 · 干细胞生物学
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BIOSENSORS & BIOELECTRONICS · 2019 · IF 9.518

Ultrasensitive aptamer-based protein assays based on one-dimensional core-shell nanozymes

Rui Zhang,Na Lu,Jiaxing Zhang,Ruohong Yan,Jie Li,Lihua Wang,Na Wang,Min Lv,Min Zhang

In enzyme-based immunoassys, the use of natural enzyme has been remarkably restricted by the inconvenience in preparation and storage, especially for point-of-care testing. Nanozymes, which can mimic the functions of natural enzymes, have been regarded as promising alternatives due to their robust stability and convenience in fabrication. Here we fabricated one-dimensional Fe 3 O 4 @C core-shell nanostructures via a solvent-thermal method. Thus prepared nanocomposites showed excellent peroxidase-like activity, capable of catalyzing chromogenic substrates into colored products in the presence of H 2 O 2 . We then developed a nanozyme-linked aptamer sorbent assay (NLASA) in a sandwich format, in which the as-prepared Fe 3 O 4 @C nanowires were employed as catalytic labels for colorimetric detection by naked eyes. In the detection of platelet-derived growth factor BB (PDGF-BB), this assay reliably exhibited detection limits as low as 10 fM, with a working range from 10 fM to 100 nM. By incorporating G-quadruplex-hemin DNAzyme with Fe 3 O 4 @C nanowires, the detection limit could be further lowered to 50 aM. The detection limit of PDGF-BB in 50% human serum was 100 fM. This ultrasensitive, cost-effective and easy-to-operate sensing platform offers new opportunities for protein detection in clinical diagnosis.

研究领域: 生物化学 · 纳米技术 · 分析化学 · 临床诊断
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF CONTROLLED RELEASE · 2024 · IF 10.5

Bioactive peptide relieves glucocorticoid-induced osteoporosis by giant macrocyclic encapsulation

Yuna Shang,Qingrun Zhu,Jiaming Ding,Liang Zhao,Fan Zhang,Jiayi Lu,Yinyin Feng,Jiayu Wang,Zhixue Liu,Mingjie Kuang,Chunju Li

Bioactive peptides play a crucial role in the field of regenerative medicine and tissue engineering. However, their application in vivo and clinic is hindered by their poor stability, short half-life, and low retention rate. Herein, we propose a novel strategy for encapsulating bioactive peptides using giant macrocycles. Platelet-derived growth factor (PDGF) bioactive mimicking peptide Nap-FFGVRKKP ( P ) was selected as the representative of a bioactive peptide. Quaterphen[4]arene ( 4 ) exhibited extensive host-guest complexation with P , and the binding constant was (1.16 ± 0.10) × 10 7  M −1 . In vitro cell experiments confirmed that P  +  4 could promote the proliferation of BMSCs by 2.27 times. Even with the addition of the inhibitor dexamethasone (Dex), P  +  4 was still able to save 76.94% of the cells in the control group. Compared to the Dex group, the bone mass of the mice with osteoporosis in the P  +  4 group was significantly increased. The mean trabecular thickness (Tb.Th) increased by 17.03%, and the trabecular bone volume fraction (BV/TV) values increased by 40.55%. This supramolecular bioactive peptide delivery strategy provides a general approach for delivering bioactive peptides and opens up new opportunities for the development of peptide-based drugs.

CAS / MDL: 130-22-3 62669-70-9
研究领域: 再生医学 · 组织工程 · 药学 · 骨骼生物学 · 药物递送系统
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Acta Biomaterialia · 2022 · IF 10.633

Endothelialized microvessels fabricated by microfluidics facilitate osteogenic differentiation and promote bone repair

Jiayuan Wang,Huan Wang,Yong Wang,Zhao Liu,Zexi Li,Jiaying Li,Qixin Chen,Qingchen Meng,Wenmiao Will Shu,Junxi Wu,Can Xiao,Fengxuan Han,Bin Li

In bone tissue engineering, vascularization is one of the critical factors that limit the effect of biomaterials for bone repair . While various approaches have been tried to build vascular networks in bone grafts, lack of endothelialization still constitutes a major technical hurdle. In this study, we have developed a facile technique to fabricate endothelialized biomimetic microvessels (BMVs) from alginate-collagen composite hydrogels within a single step using microfluidic technology. BMVs with different sizes could be readily prepared by adjusting the flow rate of microfluids. All BMVs supported perfusion and outward penetration of substances in the tube. Endothelial cells could adhere and proliferate on the inner wall of tubes. It was also found that the expression of CD31 and secretion of BMP-2 and PDGF-BB were higher in the rat umbilical vein endothelial cells (RUVECs) in BMVs than those cultured on hydrogel. When co-cultured with bone marrow mesenchymal stem cells (BMSCs), endothelialized BMVs promoted the osteogenic differentiation of BMSCs compared to those in acellular BMV group. In vivo , markedly enhanced new bone formation was achieved by endothelialized BMVs in a rat critical-sized calvarial defect model compared to those with non-endothelialized BMVs or without BMVs. Together, findings from both in vitro and in vivo studies have proven that endothelialized BMVs function to facilitate osteogenesis and promote bone regeneration , and therefore might present an effective strategy in bone tissue engineering. Statement of significance In bone tissue engineering, limited vascularization is one of the critical factors that limit the effect of biomaterials for bone repair. In this study, we developed a facile technique to fabricate endothelialized biomimetic microvessels (BMVs) from alginate-collagen composite hydrogels within a single step using microfluidic technology. Both in vitro and in vivo studies have proven that endothelialized BMVs function to facilitate osteogenesis and promote bone regeneration, and therefore might present an effective strategy in bone tissue engineering.

研究领域: 组织工程 · 生物医学工程 · 再生医学 · 骨生物学 · 微流控技术
✓ 已验证 DOI PubMed 高影响因子
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Journal of Materials Chemistry B · 2019 ·Vol. 7 ·期 18 ·2954-2961 · IF 5.047

A skin-inspired 3D bilayer scaffold enhances granulation tissue formation and anti-infection for diabetic wound healing

Wenbing Wan,Feng Cai,Jiayu Huang,Shixuan Chen,Qi Liao

Diabetic wounds are characterized by sustained chronic inflammation, and decreased granulation tissue formation and vascularization, and it is a great challenge for researchers to promote chronic wound healing. In this study, we fabricate a bilayer skin substrate composed of a top layer made of silver-loaded gelatine cryogel and a bottom layer made of a platelet-derived growth factor-BB (PDGF-BB) loaded 3D printed gelatine scaffold for diabetic wound healing. In vitro, the concentration of loaded silver has no effect on the proliferation of fibroblasts, keratinocytes and immune cells cocultured with silver-loaded 3D bilayer hydrogel extract medium. In addition, the CFU quantification results showed that the release of silver nanoparticles was able to significantly kill bacteria including Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. In vivo, PDGF-BB-loaded scaffolds, and silver and PDGF-BB coloaded scaffolds were able to accelerate wound closure, re-epithelialization, granulation tissue formation and angiogenesis compared to the scaffold and silver-loaded scaffold groups at each indicated time point. The silver and PDGF-BB coloaded bilayer hydrogel scaffolds show great potential for promoting diabetic wound healing and against bacterial infections.

研究领域: 生物医学工程 · 组织工程 · 伤口愈合 · 感染控制
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Stem Cell Research & Therapy · 2022 ·Vol. 13 ·期 1 ·1-16 · IF 8.079

Identification of a new way to induce differentiation of dermal fibroblasts into vascular endothelial cells

Cui XiaoLing,Wang XiaoTan,Wen Jie,Li Xiao,Li Nan,Hao XuXiao,Zhao BaoXiang,Wu Xunwei,Miao JunYing

Background Human dermal fibroblasts (HDFs) have the potential to differentiate into vascular endothelial cells (VECs), but their differentiation rate is low and the mechanism involved is not clear. The small molecule pathway controls the phenotype of fibroblasts by activating cellular signaling pathways, which is a more convenient method in the differentiation strategy of HDFs into VECs. Methods In this study, HDFs were treated with the different doses of CPP ((E)-4-(4-(4-(7-(diethylamino)-2-oxo-2H-chromene-3-carbonyl) piperazin-1-yl) styryl)-1-methylpyridin-1-ium iodide), and the mRNA and protein levels of HDFs were detected by qPCR, Western blot, flow cytometry and immunofluorescent staining. The matrigel assays, acetylated-LDL uptake and angiogenesis assays of chick embryo chorioallantoic membrane (CAM) and hindlimb ischemia model of nude mice were performed to evaluate the functions of VECs derived from HDFs. Results Here, we report that the small chemical molecule, CPP, can effectively induce HDFs to differentiate into VECs. First, we observed the morphological changes of HDFS treated with CPP. Flow cytometry, Western blot and qRT-PCR analyses showed that CPP effectively decreased the level of the HDFs-marker Vimentin and increased levels of the VEC-markers CD31, CD133, TEK, ERG, vWF, KDR and CDH5. Detection of the percentage of CD31-positive cells by immunofluorescent staining confirmed that CPP can effectively induce HDFs to differentiate into VECs. The results of Matrigel assays, DiI-ac-LDL uptake, angiogenesis assays on CAM and hindlimb ischemia model of nude mice showed that CPP-induced HDFs have the functions of VECs in vitro and in vivo. Western blot and qRT-PCR analysis showed that CPP induces HDFs to differentiate into VECs by promoting the expression of pro-angiogenic factors (VEGF, FGF-2 and PDGF-BB). Conclusions Our data suggest that the small chemical molecule CPP efficiently induces the differentiation of HDFs into VECs. Simultaneously, this new inducer provides a potential to develop new approaches to restore vascular function for the treatment of ischemic vascular diseases.

CAS / MDL: 3520-42-1
研究领域: 细胞生物学 · 分子生物学 · 血管生物学 · 再生医学
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