Advanced Healthcare Materials
·
2020
·Vol. 9
·期 23
·2000076
·
IF 7.367
Xuemin Liu,Yingqi Wei,Chengkai Xuan,Lei Liu,Chen Lai,Muyuan Chai,Zhaoguo Zhang,Lin Wang,Xuetao Shi
There is a great challenge in regenerating osteochondral defects because they involve lesions of both cartilage and subchondral bone, which have remarkable differences in their chemical compositions and biological lineages. Thus, considering the complicated requirements in osteochondral reconstruction, a biomimetic biphasic osteochondral scaffold (BBOS) with the layer-specific release of stem cell differentiation inducers are developed. The cartilage regeneration layer (cartilage scaffold, CS) in the BBOS contains a hyaluronic acid hydrogel to mimic the composition of cartilage, which is mechanically enhanced by host–guest supramolecular units to control the release of kartogenin (KGN). Additionally, a 3D-printed hydroxyapatite (HAp) scaffold releasing alendronate (ALN) is employed as the bone-regeneration layer (bone scaffold, BS). The two layers are bound by semi-immersion and could regulate the hierarchical targeted differentiation behavior of the stem cells. Compared to the drug-free scaffold, the MSCs in the BBOS could be promoted to differentiate into both chondrocytes and osteoblasts. The in vivo results demonstrate the strong promotion of cartilage or bone regeneration in their respective layers. It is expected that this BBOS with layer-specific inducer release can become a new strategy for osteochondral regeneration.
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Reproductive Sciences
·
2020
·Vol. 27
·期 7
·1502-1512
·
IF 2.616
Feng Xiushan,Ling Li,Zhang Wenqian,Liu Xiaohan,Wang Yaping,Luo Yanjing,Xiong Zhengai
Human amnion–derived mesenchymal stem cell (hAD-MSC) transplantation can repair ovarian injury and improve ovarian function in rats with chemotherapy-induced primary ovarian insufficiency (POI). However, ensuring that stem cells home to the ovary to improve their effects on ovarian injury is challenging. This research aimed to directly inject ovarian tissue with hAD-MSCs and improve the homing of stem cells to the ovary. The animals were divided into POI, hAD-MSC (tail vein) treatment, hAD-MSC (in situ) treatment, and control groups. POI rat models were established by intraperitoneal injection of cyclophosphamide (CTX) and busulfan (BUS). The hAD-MSCs isolated from the amnion were injected into the tail vein or ovary of POI rats. The estrous cycle, serum sex hormone levels, follicle counts, ovarian pathological changes, and proteome of the ovaries were evaluated. hAD-MSCs were successfully isolated and cultured from the amnion. Both hAD-MSC (tail vein) and hAD-MSC (in situ) transplantation increased body weight, improved the AMH levels and follicle numbers, and reduced reproductive organ injuries in POI rats. Transplantation of hAD-MSCs (in situ) upregulated 24 proteins and downregulated 4 proteins. Both hAD-MSC (tail vein) and hAD-MSC (in situ) transplantations can repair ovarian injury and improve ovarian function in rats with chemotherapy-induced POI. The paracrine proteome of hAD-MSCs in the ovarian microenvironment can protect against chemotherapy-induced damage by reducing apoptosis and promoting angiogenesis, cell proliferation, and gene expression.
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BIOMEDICINE & PHARMACOTHERAPY
·
2019
·
IF 3.743
Xiao-Jun Chen,Ying-Shan Shen,Min-Cong He,Fan Yang,Peng Yang,Feng-Xiang Pang,Wei He,Yan-ming Cao,Qiu-Shi Wei
Steroid-induced osteonecrosis of the femoral head (SONFH) is a refractory disease induced by glucocorticoids. Marrow mesenchymal stem cells (MSCs) differentiate into multiple bone matrix cells and have been used as cell-based therapies to treat ONFH. However, the osteogenesis of MSCs isolated from patients with SONFH is significantly decreased. Polydatin has been widely used in traditional Chinese remedies due to its multiple pharmacological actions. As shown in our previous study, Polydatin protects from oxidative stress and promotes BMSC migration. However, little is known about its role in BMSC (Bone marrow mesenchymal stem cells) osteogenesis; therefore, we further investigated the effect and mechanism of Polydatin in hBMSC osteogenesis. The ability of Polydatin to promote the proliferation and osteogenic differentiation of hBMSCs was determined using the MTT assay, ALP staining and the ALP activity assay. Next, qPCR and western blotting were performed to measure the levels of genes and proteins related to the osteogenesis of hBMSCs. Then, the effect of Polydatin on the nuclear translocation of β-catenin was determined using immunofluorescence staining. Polydatin (30 μM) markedly enhanced the proliferation of hBMSCs and alkaline phosphatase (ALP) activity. Additionally, it also significantly upregulated the expression of osteogenic genes (Runx2, osteopontin, DLX5, osteocalcin, collagen type I and BMP2) and components of the Wnt signaling pathway (β-catenin, Lef1, TCF7, c-jun, c-myc and cyclin D). These osteogenesis-potentiating effects of Polydatin were blocked by Noggin, an inhibitor of the BMP pathway, and DKK1, an inhibitor of the Wnt/β-catenin pathway. However, DKK1 did not affect Polydatin-induced BMP2 expression. Based on our results, Polydatin promotes the proliferation and osteogenic differentiation of hBMSCs through the BMP2-Wnt/β-catenin signaling pathway.
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Scientific Reports
·
2019
·Vol. 9
·期 1
·1-10
·
IF 4.011
Wang Yaozong,Sun Naikun,Zhang Yinlong,Zhao Bin,Zhang Zheyi,Zhou Xu,Zhou Yuanyuan,Liu Hongyi,Zhang Ying,Liu Jianguo
This study explored the applicability, cellular efficacy, and osteogenic activities of porous nano-hydroxyapatite/Poly (glycerol sebacate)-grafted maleic anhydride (n-HA/PGS-g-M) composite scaffolds. Nuclear magnetic resonance (NMR) analyses indicated that approximately 43% of the hydroxide radicals in PGS were displaced by maleic anhydride. Resonance bands at 1036 cm −1 occurred in scaffolds containing nHA powders, and peak areas increased when n-HA weight increased in PGS-M-n-HA-0.4, PGS-M-n-HA-0.5, and PGS-M-n-HA-0.6 scaffolds. The n-HA/PGS-g-M composite scaffolds exhibited porous microstructure with average pore size of 150–300 µm in scanning electron microscopy (SEM) analysis. Differential scanning calorimetry (DSC) identified the glass transition temperature (Tg) as −25–30 °C, indicative of quality resilience. The modulus of compressibility increased when n-HA content increased. Interestingly, viability of human adipose-derived stem cells (hADSCs) in vitro and expression of the osteogenic related genes RUNX2 , OCN , and COL1A1 was enhanced in the n-HA/PGS-g-M composite scaffolds compared to those factors observed in PGS-g-M scaffolds. Finally, simulated body fluid (SBF) tests indicated more apatite deposits on the surface of n-HA/PGS-g-M scaffolds compared to PGS-g-M scaffolds. Overall, porous n-HA/PGS-g-M composite scaffolds possessed acceptable biocompatibility and mechanical properties, and they stimulated hADSC cell proliferation and differentiation. Given these qualities, the composite scaffolds have potential applications in bone tissue engineering.
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ACS Biomaterials Science & Engineering
·
2019
·
IF 4.511
Lin Feng,Ying Hao,Mo Zhu,Yuanxin Zhai,Lingyan Yang,Yang Liu,Guosheng Cheng
Three-dimensional (3D) carbon-based scaffolds have rapidly risen in tissue engineering due to the excellent conductivity and unique topological structures. For specific in vivo application, it is desirable to maintain the rigidity and improve the toughness of scaffolds in response to the compression force from surrounding tissues. In light of the combined advantages of graphene and hydrogels, we here construct a 3D composite scaffold consisting of a graphene foam (GF) and a laminarin hydrogel (LAgel). The composite scaffold was fabricated by immersing the GF in an LA hydrogel precursor followed by exposure to ultraviolet (UV) radiation to form a photocross-linked LAgel surrounding the GF. This composite scaffold exhibited the improved toughness compared with the GF or LAgel. The 3D GF can support cell attachment and cell spreading of human mesenchymal stem cells (hMSCs), while the in situ-formed LAgel with cell adhesive peptide arginine–glycine–aspartic acid (RGD) conjugated can induce the cell migration. The results suggest that the approach to incorporate the LAgel with the 3D GF not only enhances the toughness of the scaffold but also offers a carrier to realize the cargo of biosignals to regulate cell behaviors, showing the potential of this composite scaffold for tissue regeneration.
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Biomaterials Science
·
2018
·Vol. 6
·期 8
·2209-2218
·
IF 5.831
Siqi Wang,Wenzhi Ren,Jianhua Wang,Zhenqi Jiang,Madiha Saeed,Lili Zhang,Aiguo Li,Aiguo Wu
At present, transmembrane glycoprotein CD133 highly expressed pancreatic cancer stem cells (PCSCs), with the features of chemotherapeutic/radiotherapeutic resistance and exclusive tumorigenic potential, are considered as the primary cause of metastasis and recurrence in pancreatic cancer, and therefore are an effective target in the disease treatment. Furthermore, with the launch of precision medicine, multifunctional nanoprobes have been applied as an efficient strategy for the magnetic resonance imaging (MRI)-guided photothermal therapy (PTT) of pancreatic cancer. In this research, with the aim of achieving precise MRI-guided PTT in CD133 highly expressed PCSCs, novel bTiO2-Gd-CD133mAb nanoprobes were designed and successfully prepared by loading Gd-DOTA and CD133 monoclonal antibodies on black TiO2 nanoparticles. It was very interesting to find that the r1 relaxivity value of the nanoprobes was 34.394 mM−1 s−1, about 7.5 times that of commercial Magnevist (4.5624 mM−1 s−1), which indicates that the nanoprobes have good potential as MRI T1 contrast agents with excellent performance. Herein, CD133 highly expressed PANC-1 cells were selected and verified as PCSCs model. In vitro experiments demonstrated that the nanoprobes exhibited active-targeting ability in PANC-1 cells, and consequently could specially enhance T1-weighted MR imaging and 808 nm near-infrared (NIR)-triggered PTT efficiency in the PCSCs model. Our study not only provides a new strategy for the effective treatment of pancreatic cancer and its’ stem cells, but also further broadens the application of black TiO2 in the field of cancer theranostics.
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BIOMATERIALS
·
2018
·
IF 8.806
Guoxin Jing,Zhaojie Wang,Xizhen Zhuang,Xiaolie He,Huijun Wu,Qingxiu Wang,Liming Cheng,Zhongmin Liu,Shilong Wang,Rongrong Zhu
Graphene oxide (GO), with good hydrophilicity and biocompatibility, is widely explored as a carrier for various factors in the field of stem cell differentiation . However, its function of sustaining the stemness of mouse embryonic stem cells (mESCs) and the underlying mechanisms of this process remains undiscovered. Herein, we explored the biofunction of GO on mESCs and revealed the involved signaling pathways and key gene. The alkaline phosphatase activity detection, pluripotency genes quantification and the teratomas formation in vivo confirmed that GO nanosheets could sustain the self-renewal ability of mESCs instead of influencing its pluripotency . The underlying signaling pathways were uncovered by RNA-seq that integrin signaling pathway was involved in the biofunction of GO on mESCs and Vinculin turned to be a key gene for the effect of GO. Further experiments confirmed that the downregulation of Vinculin influenced the fate of mESCs through decreasing the expression of MEK1. Altogether, the study demonstrated for the first time that GOs hold the potential in sustaining the self-renewal of mESCs and clarified the mechanism of this function, which make it play a new role in stem cell research and regenerative medicine .
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Acta Biomaterialia
·
2018
·
IF 6.383
Ye He,Caiyun Mu,Xinkun Shen,Zhang Yuan,Ju Liu,Weizhen Chen,Chuanchuan Lin,Bailong Tao,Bin Liu,Kaiyong Cai
Titanium (Ti) and Ti-alloys were widely used in clinic orthopedics, however, the insufficient bone formation surrounding Ti-based implants still limited their biological performances. Surface modification of Ti substrates is essential to improve their interactions with bone-forming cells and bone tissue. In this study, we modified Ti substrates by coating peptide LL-37 onto micro-structured Ti substrates and aimed to (i) induce mesenchymal stem cells (MSCs) migration both in vitro and in vivo , (ii) facilitate osteogenic differentiation of MSCs and new bone formation. The surface micro-structured Ti substrates with hydroxyapatite deposition were fabricated by a two-step method including micro-arc oxidation (MAO) and hydrothermal treatment. LL-37 was loaded on micro-structured Ti substrates with the assistance of polydopamine coating. We confirmed that surface-modified Ti substrates benefited viability, adhesion, migration and osteogenic differentiation of MSCs in vitro . In a femur-defect rat model, the surface-modified Ti implants effectively induced CD29 + /CD90 + positive cells migration in one week after implantation. According to the results of H&E, Masson’s trichrome staining and immunohistochemical staining of OCN , OPN and collagen I, the targeted Ti implants exhibited significant new bone formation after implantation for 4 weeks. These results indicate that the surface modification of Ti samples facilitated bone formation through MSCs recruitment. Statement of Significance The inherent surface bioinertness of titanium (Ti) and Ti-alloys still limits their biological performances in clinical applications. Recently, the strategy of mesenchymal stem cells (MSCs) recruitment has been proposed to improve the osteointegration of bone implants. Herein, we reports the surface modification of Ti implants from the point of MSCs recruitment. Peptide LL-37 was coated on micro-structured Ti substrates to (i) recruit MSCs, (ii) regulate bio-physiological performance of MSCs, and (iii) facilitate bone formation in vivo. Our results improve the understanding of the interaction between Ti implants and MSCs, and provide a promising strategy of MSCs recruitment in the design of bone repair related biomaterials.
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INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
·
2015
·
IF 4.046
Jie Ding,Zihua Tang,Jiarong Chen,Haosong Shi,Jianling Chen,Cuicui Wang,Cui Zhang,Liang Li,Ping Chen,Jinfu Wang
Sensorineural hearing loss and vestibular dysfunction have become the most common forms of sensory defects. Stem cell-based therapeutic strategies for curing hearing loss are being developed. Several attempts to develop hair cells by using chicken utricle stromal cells as feeder cells have resulted in phenotypic conversion of stem cells into inner ear hair-cell-like cells. Here, we induced the differentiation of human embryonic stem cells (hESCs) into otic epithelial progenitors (OEPs), and further induced the differentiation of OEPs into hair-cell-like cells using different substrates. Our results showed that OEPs cultured on the chicken utricle stromal cells with the induction medium could differentiate into hair-cell-like cells with stereociliary bundles. Co-culture with stromal cells, however, may be problematic for subsequent examination of the induced hair-cell-like cells. In order to avoid the interference from stromal cells, we cultured OEPs on laminin with different induction media and examined the effects of the induction medium on the differentiation potentials of OEPs into hair-cell-like cells. The results revealed that the culture of OEPs on laminin with the conditioned medium from chicken utricle stromal cells supplemented with EGF and all-trans retinoic acid (RA) could promote the organization of cells into epithelial clusters displaying hair-cell-like cells with stereociliary bundles. These cells also displayed the expected electrophysiological properties.
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CRYSTENGCOMM
·
2013
·Vol. 15
·期 41
·8330-8336
·
IF 3.879
Yamei Li,Shidong Ji,Yanfeng Gao,Hongjie Luo,Shaotang Li,Meng Jiang,Yijie Zhou,Rong Li,Bingbing Wang,Ping Jin
This paper presents a novel vapor–solid growth approach of stem-like 1D vanadium oxide nanostructures in a core-regenerated fashion on VO2@TiO2 core–shell rods under a very low temperature (400 °C). The composition and microstructure of the as-grown nanostructures were analyzed by HRTEM, EDS and XPS, confirming the vapor–solid mechanism. The confinement effect of the shell was analyzed by varying experimental parameters (coating thickness and heating rate), and the shell was found to play a critical role in generating and accumulating vapor with supersaturated concentration for the nanocrystal nucleation. Additionally, PVP was added as a surface modifier to favor the growth, probably by forming carbonaceous/nitrogen gaseous species as carrier media, as deduced by FTIR analysis. By exploring the impact of different heating rates, we found that the mass transfer process was facilitated only using a relatively high heating rate (>1.33 °C s−1). However, such a growth was still limited only within the early stages (~15 min), because the confined vacuum interface will disappear with the progress of the crystallization of the nanoporous anatase shell. A unique 1D rods to 2D nano-flakes evolution can be achieved by increasing the heating rate from 1.3 °C s−1 to over 8 °C s−1. These findings provide a valuable understanding on the thermodynamics and kinetics during an unique VS based nanocrystal growing process, and also showed a new method to obtain hierarchical heterogeneous nanostructures.
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RSC Advances
·
2015
·Vol. 5
·期 38
·30268-30274
·
IF 3.84
Xiaopeng Huang,Yuqin Li,Xiang Huang,Yaowen Chen,Wenhua Gao
An ingenious sensing strategy for detecting thrombin in human serum has been developed on the basis of a hairpin DNA sequence and resonance light scattering (RLS) technique. A thrombin aptamer sequence was embedded inside the hairpin DNA strand (H-eTBA), which was designed to be the loop-stem structure. Moreover, methylene blue (MB) was utilized as the RLS signal indicator according to its different affinity to single or double stranded DNA. Upon the addition of thrombin, the thrombin aptamer inside H-eTBA interacted specifically with thrombin. Thus the conformation of H-eTBA would change. After the introduction of the DNA strand (CTBA), which was complementary to H-eTBA, the amount of double stranded DNA would decrease as a consequence. Later when MB solution was added, the RLS signal would present various response values based on different amounts of thrombin. The determination of thrombin in human serum could be obtained with a detection limit of 0.32 nM and this specific sensor could be applied to detect thrombin practically. Furthermore, this aptasensor showed quite good selectivity and simplicity toward thrombin. Finally, the proposed sensing method showed its superiority with selectivity and practicability, which could be used as a simple platform for thrombin detection.
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ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Dongdong Xiao,Hao Yan,Qiong Wang,Xiangguo Lv,Ming Zhang,Yang Zhao,Zhe Zhou,Jiping Xu,Qian Sun,Kang Sun,Wei Li,Mujun Lu
Bladder acellular matrix graft-alginate dialdehyde-gelatin hydrogel-silk mesh (BAMG-HS) encapsulated with adipose-derived stem cells (ASCs) was evaluated in a rat model of augmentation cystoplasty, including BAMG-HS-ASCs (n = 18, subgroup n = 6 for 2, 4, and 12 weeks), acellular BAMG-HS (n = 6 for 12 weeks) and cystotomy control (n = 6 for 12 weeks) groups. Equipped with good cytocompatibility and superior mechanical properties (elastic modulus: 5.33 ± 0.96 MPa, maximum load: 28.90 ± 0.69 N), BAMG-HS acted a trilayer “sandwich” scaffold with minimal interference in systemic homeostasis. ASCs in BAMG-HS promoted morphological and histological bladder restoration by accelerating scaffold degradation (p < 0.05), ameliorating fibrosis (p < 0.05) and inflammation (p < 0.01). Additionally, ASCs facilitated the recovery of bladder function by enhancing smooth muscle regeneration (p < 0.05), innervation (p < 0.01) and angiogenesis (p < 0.001). Except for a small number of endothelium-differentiated ASCs, the pro-angiogenic effects of ASCs were mainly related to ERK1/2 phosphorylation in the downstream of SDF-1α/CXCR4 pathway.
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