Materials Today Bio
·
2023
·
IF 8.2
Yue Zhao,Lutong Song,Mengchen Li,Haoran Peng,Xinyi Qiu,Yuyang Li,Bijun Zhu,Chao Liu,Shuangshuang Ren,Leiying Miao
Vital pulp preservation, which is a clinical challenge of aseptic or iatrogenic accidental exposure of the pulp, in cases direct pulp capping is the main technology. Human dental pulp stem cells (hDPSCs) play a critical role in pulp tissue repair, but their differentiative ability could be inhibited by the potential infection and inflammatory response of the exposed pulp. Therefore, inflammatory regulation and differentiated promotion of hDPSCs are both essential for preserving living pulp teeth. In this study, we constructed a functional dental pulp-capping hydrogel by loading cerium oxide nanoparticles (CNPs) and dentin matrix protein-1 (DMP1) into an injectable Fmoc–triphenylalanine hydrogel (Fmoc-phe3 hydrogel) as CNPs/DMP1/Hydrogel for in situ drugs delivery. With a view to long-term storage and release of CNPs (anti-inflammatory and antioxidant) to regulate the local inflammatory environment and DMP1 to promote the regeneration of dentin. Results of CCK-8, LDH release, hemolysis, and Live/Dead assessment of cells demonstrated the good biocompatibility of CNPs/DMP1/Hydrogel. The levels of alkaline phosphatase activity, quantification of the mineralized nodules, expressions of osteogenic genes and proteins demonstrated CNPs/DMP1/Hydrogel could protect the activity of hDPSCs’ osteogenic/dentinogenic differentiation by reducing the inflammation response via releasing CNPs. The therapy effects were further confirmed in rat models, CNPs/DMP1/Hydrogel reduced the necrosis rate of damaged pulp and promoted injured pulp repair and reparative dentin formation with preserved vital pulps. In summary, the CNPs/DMP1/Hydrogel composite is an up-and-coming pulp-capping material candidate to induce reparative dentin formation, as well as provide a theoretical and experimental basis for developing pulp-capping materials.
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高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Abdullkhaleg Ali Albashari,Yan He,Yu Luo,Xingxiang Duan,Jihea Ali,Mingchang Li,Dehao Fu,Yangfan Xiang,Youjian Peng,Song Li,Lihua Luo,Xingjie Zan,Tushar Kumeria,Qingsong Ye
Spinal cord injury (SCI) commonly induces nerve damage and nerve cell degeneration. In this work, a novel dental pulp stem cells (DPSCs) encapsulated thermoresponsive injectable hydrogel with sustained hydrogen sulfide (H 2 S) delivery is demonstrated for SCI repair. For controlled and sustained H 2 S gas therapy, a clinically tested H 2 S donor (JK) loaded octysilane functionalized mesoporous silica nanoparticles (OMSNs) are incorporated into the thermosensitive hydrogel made from Pluronic F127 (PF-127). The JK-loaded functionalized MSNs (OMSF@JK) promote preferential M2-like polarization of macrophages and neuronal differentiation of DPSCs in vitro. OMSF@JK incorporated PF-127 injectable hydrogel (PF-OMSF@JK) has a soft consistency similar to that of the human spinal cord and thus, shows a high cytocompatibility with DPSCs. The cross-sectional micromorphology of the hydrogel shows a continuous porous structure. Last, the PF-OMSF@JK composite hydrogel considerably improves the in vivo SCI regeneration in Sprague–Dawley rats through a reduction in inflammation and neuronal differentiation of the incorporated stem cells as confirmed using western blotting and immunohistochemistry. The highly encouraging in vivo results prove that this novel design on hydrogel is a promising therapy for SCI regeneration with the potential for clinical translation.
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MATERIALS & DESIGN
·
2023
·
IF 8.4
Chang Zhao,Xianyan Wei,Weijian Kong,Yin Zhao,Jingpu Yang,Jinzhang Cheng,Zonggui Wang
Allergic rhinitis (AR) has gained an increasing prevalence over the years, a more effective and safe treatment strategy need to be carried out. Mesenchymal stem cell derived extracellular vesicles (MSC-EVs) show great therapeutic potential for AR, however, their low bioavailability through currently available delivery methods inhibits the process of clinical application. In the present study, an injectable thermosensitive chitosan based hydrogel was developed as an intranasal delivery platform for bone marrow-derived MSC-EVs (BMSC-EVs) and BMSC-EVs were proved to be effective in treating AR animal models for the first time. Our results showed that the BMSC-EVs loaded thermosensitive chitosan based hydrogel (BMSC-EVs@CHI hydrogel) could be prepared easily by ion-crosslinking and its gelation properties were suitable for intranasal administration. In vitro studies demonstrated that the BMSC-EVs@CHI hydrogel could achieve sustained release of BMSC-EVs mainly by degradation control and preserve the therapeutic functions of BMSC-EVs. An in vivo experiment revealed that the BMSC-EVs@CHI hydrogel could enhance the efficacy of BMSC-EVs for AR alleviation. This study provides a suitable delivery platform for BMSC-EVs-based AR therapy.
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ADVANCED FUNCTIONAL MATERIALS
·
2023
·
IF 19
Enhao Lu,Xi Yang,Tao Wang,Xueli Huang,Yiting Chen,Rui Wang,Kuankuan Luo,Zhiwen Zhang,Xiaoxi Lin,Xianyi Sha
Tissue repair and regeneration in ischemic areas require effective strategies for angiogenesis and microcirculation reconstruction. In this research, extracellular vesicles (EVs) derived from hemangioma stem cells (HemSC) are used as bio-functional materials for angiogenesis. In addition, a novel thermo-sensitive hydrogel based on chitosan (CS) and modified with hyaluronic oligosaccharides (oHA), is specially developed as an ideal carrier of HemSC-EVs. The oHA/CS gel provides a sustained-release delivery system for EVs, enhances the angiogenic function of HemSC-EVs, and exerts other bio-functions to comprehensively accelerate tissue repair. The physical properties of EVs@oHA/CS gel proved to be soft, highly elastic deformable, biocompatible, and can maintain the shape and structure of EVs. In vitro co-culture assay verifies the angiogenic effect of EVs@oHA/CS gel , and this effect is also evaluated in a diabetic wound model. Compared to untreated group, the EVs@oHA/CS gel group has only 26.9% wound area on day 14, and 226.8% blood flux mark on day 17. Pharmacological mechanisms of HemSC-EVs are predicted by RNA-seq, and cluster analysis of miRNAs predicted targets presents several up-regulated biological processes involving in angiogenesis and wound healing. In conclusion, it is suggested that EVs@oHA/CS gel as a satisfying therapeutic system for microcirculation reconstruction in tissue repair.
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ADVANCED FUNCTIONAL MATERIALS
·
2023
·
IF 19
Ruiqi Li,Lian Chen,Qin Ji,Qing Liang,Ying Zhu,Wei Fu,Tianyou Chen,Hongwei Duan,Wenshan He,Zushun Xu,Xiaofang Dai,Jinghua Ren
Radiotherapy is identified as a crucial treatment for patients with glioblastoma, but recurrence is inevitable. The efficacy of radiotherapy is severely hampered partially due to the tumor evolution. Growing evidence suggests that proneural glioma stem cells can acquire mesenchymal features coupled with increased radioresistance. Thus, a better understanding of mechanisms underlying tumor subclonal evolution may develop new strategies. Herein, data highlighting a positive correlation between the accumulation of macrophage in the glioblastoma microenvironment after irradiation and mesenchymal transdifferentiation in glioblastoma are presented. Mechanistically, elevated production of inflammatory cytokines released by macrophages promotes mesenchymal transition in an NF- κ B-dependent manner. Hence, rationally designed macrophage membrane-coated porous mesoporous silica nanoparticles (MMNs) in which therapeutic anti-NF- κ B peptides are loaded for enhancing radiotherapy of glioblastoma are constructed. The combination of MMNs and fractionated irradiation results in the blockage of tumor evolution and therapy resistance in glioblastoma-bearing mice. Intriguingly, the macrophage invasion across the blood-brain barrier is inhibited competitively by MMNs, suggesting that these nanoparticles can fundamentally halt the evolution of radioresistant clones. Taken together, the biomimetic MMNs represent a promising strategy that prevents mesenchymal transition and improves therapeutic response to irradiation as well as overall survival in patients with glioblastoma.
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ADVANCED MATERIALS
·
2023
·
IF 29.4
Yanan Zhang,Renwang Sheng,Jialin Chen,Hongmei Wang,Yue Zhu,Zhicheng Cao,Xinyi Zhao,Zhimei Wang,Chuanquan Liu,Zhixuan Chen,Po Zhang,Baian Kuang,Haotian Zheng,Chuanlai Shen,Qingqiang Yao,Wei Zhang
Silk fibroin (SF) and sericin (SS), the two major proteins of silk, are attractive biomaterials with great potential in tissue engineering and regenerative medicine. However, their biochemical interactions with stem cells remain unclear. In this study, multiomics are employed to obtain a global view of the cellular processes and pathways of mesenchymal stem cells (MSCs) triggered by SF and SS to discern cell–biomaterial interactions at an in-depth, high-throughput molecular level. Integrated RNA sequencing and proteomic analysis confirm that SF and SS initiate widespread but distinct cellular responses and potentiate the paracrine functions of MSCs that regulate extracellular matrix deposition, angiogenesis, and immunomodulation through differentially activating the integrin/PI3K/Akt and glycolysis signaling pathways. These paracrine signals of MSCs stimulated by SF and SS effectively improve skin regeneration by regulating the behavior of multiple resident cells (fibroblasts, endothelial cells, and macrophages) in the skin wound microenvironment. Compared to SS, SF exhibits better immunomodulatory effects in vitro and in vivo, indicating its greater potential as a carrier material of MSCs for skin regeneration. This study provides comprehensive and reliable insights into the cellular interactions with SF and SS, enabling the future development of silk-based therapeutics for tissue engineering and stem cell therapy.
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International Journal of Nanomedicine
·
2023
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IF 8
Lijuan Lin,Xizhen Zhuang,Ruiqi Huang,Simin Song,Zhaojie Wang,Shilong Wang,Liming Cheng,Rongrong Zhu
Purpose In this study, we aim to explore the effects of graphene oxide (GO), a derivative of graphene, nanoparticles of four different sizes on the cellular fate of mouse neural stem cells (mNSCs).Methods GO NPs were characterized with transmission electron microscopy (TEM), scanning electron micrography (SEM), atomic force microscopy (AFM) and Raman Spectra analysis. The cytotoxic effects of the GO NPs of different sizes on the mNSCs were determined using CCK-8 assay, Annexin V-APC/ 7-AAD staining and EdU staining assays. We investigated the biological and the mechanisms of GO NPs on cells using immunofluorescence analysis and quantitative real-time PCR (qPCR).Results The average hydrodynamic sizes of the GO NPs were 417 nm, 663 nm, 1047 nm, and 4651 nm, with a thickness of approximately 22.5 nm, 17.7 nm, 22.4 nm, and 13.4 nm, respectively. GO NPs of all sizes showed low cytotoxicity at a concentration of 20 μg/mL on the mNSCs. Immunostaining demonstrated that treatment with GO NPs, especially the 663 nm ones, enhanced the self-renewal ability of mNSCs in the absence of EGF and bFGF. Under differentiation medium conditions that are free of mitogenic factors, all the GO NPs, particularly the 4651 nm ones, increased the expression level of Tuj1 and GFAP. With regards to the migration ability, we found that 417 nm GO-NP-treated mNSCs migrated over a longer distance than the control group obviously. In addition, higher expression of Rap1, Vinculin and Paxillin was observed in the GO NP-treated groups compared to the control group. mRNA-Sequence analysis and Western blotting results suggested that the 4651 nm GO NPs triggered positive neuronal differentiation through phosphorylation of ERK1/2 by the downregulating of TRPC2.Conclusion GO NPs play an important role in the applications of inducing self-renewal and differentiation of mNSC, and are promising in the future for further studies.
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International Journal of Nanomedicine
·
2023
·
IF 8
Hongxiang Wei,Jinyuan Chen,Shenglin Wang,Feihuan Fu,Xia Zhu,Chaoyang Wu,Zhoujie Liu,Guangxian Zhong,Jianhua Lin
Purpose The primary goal of the present study was to develop the nano-drug consisting of doxorubicin and exosome derived from mesenchymal stem cells, and to explore its effect on osteosarcoma in vitro.Methods The exosomes were isolated from bone marrow MSCs (BM-MSCs) by an Exosome Isolation Kit. The exosome-loaded doxorubicin (Exo-Dox) was prepared by mixing exosome with Dox-HCl, desalinizing with triethylamine and then dialyzing against PBS overnight. The nanoparticle tracking analysis (NTA) and transmission electron microscope (TEM) were used to characterize of the exosome and Exo-Dox. The cytotoxicity of Exo-Dox was determined by CCK-8 assay. Further, the cellular uptake of different drugs was analyzed using inverted fluorescence microscope and flow cytometry.Results The typical exosome structures can be observed by TEM. After loading with doxorubicin, its size is larger than free exosome. Compared with the free Dox, the prepared Exo-Dox showed enhanced cellular uptake efficiency and anti-tumor effect in osteosarcoma MG63 cell line but low cytotoxicity in myocardial H9C2 cell line.Conclusion The prepared Exo-Dox could be used as an excellent chemotherapeutic drug for treatment of osteosarcoma in vitro. Considering the tumor-homing feature of BM-MSCs, the Exo-Dox may be a good candidate for targeted osteosarcoma treatment in future study.
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高影响因子
ACS Biomaterials Science & Engineering
·
2018
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IF 4.432
Hongjie Huang,Xiaoqing Hu,Xin Zhang,Xiaoning Duan,Jiying Zhang,Xin Fu,Linghui Dai,Lan Yuan,Chunyan Zhou,Yingfang Ao
Synovium-derived mesenchymal stem cells (SMSCs) are attractive tissue-specific cells for cartilage regeneration because of their easy availability, higher chondrogenic potential, and joint specificity. In the present study, we established a hybrid scaffold to codeliver SMSCs and transforming growth factor beta (TGF-β), which can integrate the scaffolds, the growth factor, and the autogenous cells within rabbit cartilage defects. A chitosan hydrogel and a decellularized bone matrix were used to fabricate the gel–solid duplex phase biomaterials, which were proven to retain more cells, promote tissue integration, and provide mechanical support. In vitro experiments demonstrated that this hybrid scaffold could release TGF-β in a controlled biphasic pattern, which can promote cell proliferation and chondrogenic differentiation of loaded rabbit SMSCs. For in vivo experiments, we filled cartilage defects with the hybrid materials, delivering autogenous SMSCs and TGF-β simultaneously via chitosan’s sol–gel transition. Histological analysis, magnetic resonance imaging, and nanoindentation assessment indicated superior cartilage regeneration using this codelivery system compared with that from routine microfracture or control delivery scaffolds. Beyond cartilage regeneration, the easy preparation, favorable biophysical properties, and controlled release ability make this codelivery system applicable to transport other tissue-specific cells or biofactors for tissue engineering.
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2019
·Vol. 107
·期 11
·2414-2424
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IF 3.221
Xiaopei Wu,Honglian Dai,Chao Xu,Langlang Liu,Shipu Li
Biomaterials can be used as carriers of antioxidant or drug to the oxidative injury site of tissue and decrease intracellular oxidative stress levels, however, low dosage delivery or unstable molecular structure of antioxidant or drug limited the long-term sustained release. A chemically stable antioxidant molecule is essential to serve as antioxidant structure components of biomaterials that may provide the relatively high antioxidant content and persisting local antioxidant release with the degradation of materials. In this study, we used citric acid modified polyvinyl alcohol (PVA-C) as a model biomaterial to investigate the role of citric acid on the material stimulated antioxidant and anti-inflammatory effects. In cellular-based assays, PVA-C extracts showed a protective effects on bone marrow mesenchymal stem cells (BMSCs) under oxidative stress. It could enhance the antiapoptotic ability of stem cells by inhibiting reactive oxygen species. Further studies revealed that PVA-C extracts upregulated the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) and superoxide dismutase [Mn] (SOD2). in vivo animal assays, PVA-C extracts showed significant inhibitory effects on the oxidative stress and inflammatory reaction which were induced by lipopolysaccharide (LPS). These findings suggest that the citric acid modified polymer can regulate the redox signaling of stem cells and tissues by the release of citric acid from materials, leading to enhanced oxidative stress-induced degenerative diseases and inflammatory diseases therapy.
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PHARMAZIE
·
2018
·Vol. 73
·期 12
·729-732
·
IF 1.016
Wang YB.,Sun B.,Han B.
Malignant melanoma is a highly lethal disease, and advanced stages of melanoma have proven to be resistant to many chemotherapeutic drugs including temozolomide and paclitaxel. Cancer stem cells (CSCs) have been identified and isolated in different cancers including melanoma, and have
been proven playing important role in the drug resistance. Retinoic acid (RA) is a promising anticancer agent, which can induce differentiation of CSCs. The main purpose of the present study was to evaluate the possible RA-induced differentiation of melanoma CSCs and sensitization of melanoma
CSCs to paclitaxel. Our results show that CSCs of human melanoma A375 cells was more tolerant to paclitaxel than other non-CSCs melanoma cells. On the contrary, RA had stronger inhibitory effect on melanoma CSCs than on non-CSCs. At the same time, RA could arrest the cell cycle of CSCs and
reduce the expression of Sox-2, Oct-4 in CSCs of melanoma, thereby induced the differentiation of CSCs and increased its sensitivity to paclitaxel. With this study we concluded that RA increases the anticancer effect of paclitaxel by inducing differentiation of cancer stem cells in melanoma,
and the combined application of RA and paclitaxel may be more effective in the treatment of melanoma.
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Biomaterials Science
·
2019
·Vol. 7
·期 5
·1973-1983
·
IF 5.251
Qianmin Ou,Yingling Miao,Fanqiao Yang,Xuefeng Lin,Li-Ming Zhang,Yan Wang
In bone tissue engineering, it is important for biomaterials to promote the osteogenic differentiation of stem cells to achieve tissue regeneration. Therefore, it is critical to develop biomaterials with excellent cytocompatibility and osteoinductive ability. In our previous study, we found a zein/gelatin electrospinning scaffold with good biocompatibility, but low osteoinductive ability for human periodontal ligament stem cells (hPDLSCs). Therefore, herein, we fabricated novel zein/gelatin/nanohydroxyapatite (zein/gelatin/nHAp) nanofibrous membranes to overcome the drawbacks of the zein/gelatin scaffold. The results showed that the surface wettability of the zein/gelatin/nHAp nanofiber membranes was increased. Moreover, the inclusion of nHAp facilitated the attachment, proliferation, and osteogenic differentiation of hPDLSCs. Overall, the zein/gelatin/nHAp nanofiber membranes showed good biocompatibility and osteoinductive activity for hPDLSCs in vitro and in vivo; this suggested potential applications of these membranes in bone tissue engineering.
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