Materials Science & Engineering C-Materials for Biological Applications
·
2019
·
IF 4.959
Zetao Wang,Ruiming Liang,Xianfang Jiang,Jiali Xie,Peian Cai,Haimin Chen,Xintang Zhan,Danqing Lei,Jinmin Zhao,Li Zheng
Nanofibers as niche-biomimetic scaffolds hold promise in guided bone regeneration (GBR). Here we fabricated poly (lactic- co -glycolic acid) (PLGA)/poly(caprolactone) (PCL)-doped octacalcium phosphate (OCP) nanofiber membranes via electrospinning and investigated the osteogenic behavior of marrow mesenchymal stem cells (MSCs) on the membranes. By adjusting different ratio of OCP to PLGA/PCL, three hybrid stents including PLGA/PCL, PLGA/PCL/2 wt%OCP, PLGA/PCL/4wt%OCP were successfully prepared. The PLGA/PCL/OCP membranes showed a decrease in fiber diameter compared with PLGA/PCL, leading to enhanced mechanical strength. In-vitro studies showed that PLGA/PCL/OCP membranes better supported cell adhesion, spreading and proliferation than PLGA/PCL. The incorporation of OCP via electrospinning also endowed the membranes with osteoinductive capacity, as evidenced by activation of ALP activity, increased gene expression of bone specific markers (such as Runx2 , ALP , Col 1a1 , OPN , OCN , BMP2 ), and mineral nodules formation compared to PLGA/PCL. Comparatively, PLGA/PCL/4wt%OCP showed better mechanical and biological performance than PLGA/PCL/2 wt%OCP, demonstrating the role of OCP in nanofiber membranes. Thus, the electrospun PLGA/PCL/OCP nanofiber membranes can be potentially developed as a promising hybrid stent for GBR.
研究领域:
生物材料
·
组织工程
·
干细胞生物学
·
生物医学工程
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2021
·Vol. 10
·期 20
·2100985
·
IF 9.933
Yuanyuan Jia,Peiliang Shen,Tao Yan,Weijia Zhou,Jia Sun,Xin Han
Robust isolation of cancer stem cells (CSCs) in a high-throughput, label-free manner is critical for understanding tumor heterogeneity and developing therapeutic strategies targeting CSCs. Cell-mechanics-based microfluidic sorting systems provide efficient and specific platforms for investigation of stem cell-like characteristics on the basis of cell deformability and cell-substrate adhesion properties. In the present study, a microfluidic tandem mechanical sorting system is developed to enrich CSCs with high flexibility and low adhesive capacity. In the integrated microfluidic system, cancer cells are driven by hydrodynamic forces to flow continuously through two featured devices, which are functionalized with sequentially variable microbarriers and surface-coated fluid mixing microchannels, respectively. Collected deformable and low-adhesive cancer cells exhibit enhanced stem cell-like properties with higher stemness and metastasis capacity both in vitro and in vivo, compared with each single device separation. Using these devices, bioactive natural compound screening targeting CSCs is performed and a potent therapeutic compound isoliquiritigenin from licorice is identified to inhibit the lung cancer stem cell phenotype. Taken together, this microfluidic tandem mechanical sorting system can facilitate drug screening targeting CSCs and the analysis of signals regulating CSC function in drug resistance.
研究领域:
生物医学工程
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癌症生物学
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药理学
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细胞生物学
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药物发现
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DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2018
·Vol. 23
·期 2
·943-953
·
IF 4.302
Yu Xiong,Hongpei Ji,Zhipeng You,Fei Yao,Rongrong Zhou,Weitao Song,Xiaobo Xia
Retinal Müller glial cells have the potential of neurogenic retinal progenitor cells, and could reprogram into retinal-specific cell types such as photoreceptor cells. How to promote the differentiation of Müller cells into photoreceptor cells represents a promising therapy strategy for retinal degeneration diseases. This study aimed to enhance the transdifferentiation of rat Müller cells-derived retinal stem cells (MC-RSCs) into photoreceptor-like cells and explore the signalling mechanism. We dedifferentiated rat Müller cells into MC-RSCs which were infected with Otx2 overexpression lentivirus or control. The positive rate of photoreceptor-like cells among MC-RSCs treated with Otx2 overexpression lentivirus was significantly higher compared to control. Furthermore, pre-treatment with Crx siRNA, Nrl siRNA, or GSK-3 inhibitor SB-216763 reduced the positive rate of photoreceptor-like cells among MC-RSCs treated with Otx2 overexpression lentivirus. Finally, Otx2 induced photoreceptor precursor cells were injected into subretinal space of N -methyl- N -nitrosourea induced rat model of retinal degeneration and partially recovered retinal degeneration in the rats. In conclusion, Otx2 enhances transdifferentiation of MC-RSCs into photoreceptor-like cells and this is associated with the inhibition of Wnt signalling. Otx2 is a potential target for gene therapy of retinal degenerative diseases.
研究领域:
神经科学
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细胞生物学
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分子生物学
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眼科学
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DOI
PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
·
2022
·
IF 11.322
Zhimo Liu,Binfan Zhao,Liucheng Zhang,Shutong Qian,Jiayi Mao,Liying Cheng,Xiyuan Mao,Zhengwei Cai,Yuguang Zhang,Wenguo Cui,Xiaoming Sun
Integrin is a widely distributed adhesion molecule on cell membrane surface, which plays a role in transferring mechanical properties signals of the extracellular matrix into cells during cell adhesion to the extracellular matrix. In this study, by introducing long-chain polyethylene glycol molecules that can be photo-crosslinked into gelatin chains, ultra-soft hydrogel that can simulate soft tissue in vivo is constructed and stimulated by "low matrix stiffness" of the integrin signaling pathway, to promote the vascularization function of stem cells. The storage modulus of the ultra-soft hydrogel at room temperature is as low as 3.24 ± 0.18 Pa and as high as 40.83 ± 1.32 Pa. In vitro experiments showed that the stiffness of hydrogel affects the activation of the phosphorylation of VEGFR by regulating the phosphorylation of integrin and further controls the activation of the ERK pathway, thus regulating the vascularization of ADSCs . In vivo experiments have proved that ADSCs encapsulated in PEG-Gel have excellent performance in repairing skin flaps. The ultra-soft hydrogel can promote the vascularization of ADSCs by activating the "extracellular matrix stiffness-integrin-VEGFR-ERK" regulatory pathway, which is a potential regenerative repair material for promoting the application of stem cells in skin flap repair.
研究领域:
生物材料
·
组织工程
·
干细胞生物学
·
再生医学
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DOI
高影响因子
Brain Sciences
·
2022
·Vol. 12
·期 12
·1620
·
IF 3.333
Ying Wei,Uwimana Alexandre,Xiang Ma
Purpose: Retinal pigment epithelial (RPE) cells are highly specialized neural cells with several functions essential for vision. Progressive deterioration of RPE cells in elderly individuals can result in visual impairment and, ultimately, blinding disease. While human embryonic stem cell-derived RPE cell (hESC-RPE) growth conditions are generally harsher than those of cell lines, the subretinal transplantation of hESC-RPE is being clinically explored as a strategy to recover the damaged retina and improve vision. The cell-adhesion ability of the support is required for RPE transplantation, where pre-polarized cells can maintain specific functions on the scaffold. This work examined four typical biodegradable hydrogels as supports for hESC-RPE growth. Methods: Four biodegradable hydrogels were examined: gelatin methacryloyl (GelMA), hyaluronic acid methacryloyl (HAMA), alginate, and fibrin hydrogels. ARPE-19 and hESC-RPE cells were seeded onto the hydrogels separately, and the ability of these supports to facilitate adherence, proliferation, and homogeneous distribution of differentiated hESC-RPE cells was investigated. Furthermore, the hydrogel’s subretinal bio-compatibility was assessed in vivo. Results: We showed that ARPE-19 and hESC-RPE cells adhered and proliferated only on the fibrin support. The monolayer formed when cells reached confluency, demonstrating the polygonal semblance, and revealing actin filaments that moved along the cytoplasm. The expression of tight junction proteins at cell interfaces on the 14th day of seeding demonstrated the barrier function of epithelial cells on polymeric surfaces and the interaction between cells. Moreover, the expression of proteins crucial for retinal functions and matrix production was positively affected by fibrin, with an increment of PEDF. Our in vivo investigation with fibrin hydrogels revealed high short-term subretinal biocompatibility. Conclusions: The research of stem cell-based cell therapy for retinal degenerative diseases is more complicated than that of cell lines. Our results showed that fibrin is a suitable scaffold for hESC-RPE transplantation, which could be a new grafting material for tissue engineering RPE cells.Keywords:hESC-RPE;transplantation;hydrogel;retinal degenerative diseases;ARPE-19
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DOI
PubMed
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-8
·
IF 4.259
Guo Dongsheng,Liu Haikun,Ruzi Aynisahan,Gao Ge,Nasir Abbas,Liu Yanli,Yang Fan,Wu Feima,Xu Guosheng,Li Yin-xiong
Congenital hyperinsulinism (CHI) is a rare genetic disorder characterized by excess insulin secretion, which results in hypoglycemia. Mutation of sulfonylurea receptor 1 (SUR1), encoded by the ABCC8 gene, is the main cause of CHI. Here, we captured the phenotype of excess insulin secretion through pancreatic differentiation of ABCC8 -deficient stem cells generated by the CRISPR/Cas9 system. ABCC8- deficient insulin-producing cells secreted higher insulin than their wild-type counterparts, and the excess insulin secretion was rescued by nifedipine, octreotide and nicorandil. Further, we tested the role of SUR1 in response to different potassium levels and found that dysfunction of SUR1 decreased the insulin secretion rate in low and high potassium environments. Hence, pancreatic differentiation of ABCC8- deficient cells recapitulated the CHI disease phenotype in vitro , which represents an attractive model to further elucidate the function of SUR1 and to develop and screen for novel therapeutic drugs.
研究领域:
遗传学
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干细胞研究
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分子生物学
·
内分泌学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 34
·7713-7722
·
IF 5.344
Long Gao,Min Yi,Min Xing,Hekai Li,Yanling Zhou,Qing Xu,Zhaowenbin Zhang,Zhanpeng Wen,Jiang Chang
Stem-cell therapy has been proved as a promising strategy for myocardial infarction (MI) treatment. However, the therapeutic efficacy is mainly limited by the cellular activity of transplanted mesenchymal stem cells (MSCs). In this study, a novel bioglass (BG)/γ-polyglutamic acid (γ-PGA)/chitosan (CS) hydrogel was obtained by in situ adding BG to stimulate the imine bond formation. And the effect of the composite hydrogel on MI therapeutic efficacy was evaluated in a rat acute myocardial infarction (AMI) model in vivo and the possible mechanism of the BG/γ-PGA/CS hydrogel for the stimulation of the intercellular interaction between MSCs and cardiomyocytes (CMs) was explored by a MSC and CM co-culture experiment in vitro. The implantation of the MSC loaded BG/γ-PGA/CS composite hydrogel in the mice AMI model showed a significant improvement in the therapeutic efficacy with improved cardiac function, attenuation of heart remodeling, reduced cardiomyocyte apoptosis and accelerated vascularization. The in vitro cell experiments demonstrated that the BG/γ-PGA/CS hydrogel activated the intercellular interaction between MSCs and CMs, which resulted in reduced cell apoptosis and enhanced angiogenesis. Silicate based bioactive hydrogels activated MSCs and cell–cell interactions in cardiac tissue after AMI and significantly enhanced the efficacy, which suggests that this bioactive hydrogel based approach is an effective way to enhance stem-cell therapy.
研究领域:
生物医学工程
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组织工程
·
干细胞治疗
·
心脏病学
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DOI
PubMed
高影响因子
Applied Bionics and Biomechanics
·
2020
·
IF 1.141
Kang Lu,Xiaodie Chen,Hong Tang,Mei Zhou,Gang He,Juan Liu,Xuting Bian,Yupeng Guo,Fan Lai,Mingyu Yang,Zhisong Lu,Kanglai Tang
Purpose. Tendon injuries are common musculoskeletal system disorders, but the ability for tendon regeneration is limited. Silk fibroin (SF) film may be suitable for tendon regeneration due to its excellent biocompatibility and physical properties. This study is aimed at evaluating the application value of bionic SF film in tendon regeneration. Methods. Tendon stem/progenitor cells (TSPCs) were isolated from rat Achilles tendon and characterized based on their surface marker expression and multilineage differentiation potential. SF films with smooth or bionic microstructure surfaces (5, 10, 15, 20 μm) were prepared. The morphology and mechanical properties of natural tendons and SF films were characterized. TSPCs were used as the seed cells, and the cell viability and cell adhesion morphology were analyzed. The tendongenesis-related gene expression of TSPCs was also evaluated using quantitative polymerase chain reaction. Results. Compared to the native tendon, only the 10, 15, and 20 μm SF film groups had comparable maximum loading and ultimate stress, with the exception of the breaking elongation rate. The 10 μm SF film group had the highest percentage of oriented cells and the most significant changes in cell morphology. The most significant upregulations in the expression of COL1A1, TNC, TNMD, and SCX were also observed in the 10 μm SF film group. Conclusion. SF film with a bionic microstructure can serve as a tissue engineering scaffold and provide biophysical cues for the use of TSPCs to achieve proper cellular adherence arrangement and morphology as well as promote the tenogenic differentiation of TSPCs, making it a valuable customizable biomaterial for future applications in tendon repair.
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DOI
PubMed
高影响因子
Biomaterials Advances
·
2024
·
IF 5.5
Zhiyi Wang,Yu Yan,Wenxin Chen,Zhiping Tan,Qingfeng Yan,Qingqing Chen,Xue Ding,Jiahua Shen,Min Gao,Yang Yang,Lulu Yu,Fuzhi Lin,Yong Fu,Xiaoqiang Jin,Xiaohua Yu
Sensorineural deafness is a hearing impairment resulting from damage to the auditory nerve or inner ear hair cells. Currently, cochlear implants (CIs) are widely used as hearing aids for sensorineural deafness patients. A fundamental limitation of cochlear implants (CIs) is that spiral ganglion neurons (SGNs) cannot be replenished. This greatly restricts the rehabilitation of sensorineural deafness. Additionally, the insertion of CIs can cause secondary cochlear damage, worsening the condition of the patients' cochlear. Therefore, a new type of neural stem cells (NSCs) loaded graphene oxide-polyaniline/GelMA (GO-PAni/GelMA) conductive hydrogel electrode for cochlear implant was fabricated via in-situ radical polymerization and cyclic UV curing technique. On the one hand, the hydrogel electrode, as a direct contact layer, helps to avoid the physical hurt for cochlear. On the other hand, NSCs were supplemented via the hydrogel carrier and neuronal differentiation was induced by electrical stimulation, which was validated by the experimental results of immunofluorescence, Phalloidin Staining and RT-qPCR. Furthermore, based on RNA sequencing and transcriptome analysis, we hypothesized that the neuronal differentiation of NSCs was adjusted by the calcium signaling pathway and GABAergic synapse. Overall, our cell loading conductive hydrogel electrode may be an effective solution to sensorineural deafness. The revelation of the mechanism of neuronal differentiation promoted by electrical stimulation provides a basis for further sensorineural deafness treatment using conductive hydrogel CI electrode.
研究领域:
生物医学工程
·
神经科学
·
材料科学
·
组织工程
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xiaoyun Peng,Wenjing Song,Zijian Yan,Wei Zhai,Li Ren
Despite their clinical success, stem cells (SCs) in the treatment of osteoarthritis (OA) are limited by lower retention efficiency and restricted paracrine function. The development of effective SCs culture and delivery systems to maintain or promote SCs paracrine function is urgently needed. In this study, we focused on gelatin microcarriers with different sizes as SCs culture scaffold for OA therapy. The effect of culturing adipose-derived stem cells (ADSCs) on different size microcarriers (180 μm and 320 μm) to promote paracrine function was evaluated. The secretome of ADSCs cultured on microcarriers more effectively regulated macrophages and chondrocytes in a direction favorable to OA healing compared to culture plates. In particular, microcarriers with ADSCs effectively reduced the coefficient of friction at the cartilage interface. Injection low-dose ADSCs without and with different size microcarriers into the knee joints in rats' OA model was achieved. Even better OA therapeutic effects were achieved by using smaller size (higher curvature) microcarriers to deliver ADSCs at low doses. Microcarrier-based cell delivery strategies offer potential solution method for OA therapy.
研究领域:
干细胞生物学
·
骨科
·
再生医学
·
组织工程
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产品关联
DOI
PubMed
高影响因子
Theranostics
·
2025
·Vol. 15
·期 9
·4135
·
IF 13.3
Ye Yuan,Longsheng Xu,Yu Zhao,Tizhen Yan,Baobiao Zhuo,Fan Bu,Qian Cai,Youjia Xu,Qing Bi,Yu Tong,Dan Xing,Di Sun,Jianhao Lin
Rationale: Osteoarthritis (OA) is a chronic joint disorder with limited treatment efficacy, necessitating innovative therapeutic strategies. This study explores one-pot-synthesized gelatin microspheres devoid of glutaraldehyde as a novel biomaterial for OA management. Focusing on the Ext1 gene, critical for cartilage development and downregulated in OA, we investigated its restoration and immune regulation using gelatin microspheres cultured with mesenchymal stem cells (MSCs). Methods: OA patients undergoing knee replacement surgery have their lateral compartment (remote zone) and medial compartment (lesion zone) cartilage collected for transcriptomic testing. The differential gene Ext1 is identified, and the expression of immune regulatory genes is examined. MSCs were cultured with gelatin microspheres to evaluate their compatibility and ability to promote cell attachment. The effects of the gelatin microspheres on Ext1 gene overexpression, immune regulation, and OA symptom mitigation were investigated through in vitro and in vivo experiments. Results: OA patients exhibit decreased expression of the Ext1 gene in the medial compartment (lesion zone) cartilage area, accompanied by abnormal expression of immune regulatory genes. The study demonstrated that the gelatin microspheres exhibited excellent compatibility with MSCs and facilitated their attachment. Culturing MSCs with the microspheres led to enhanced overexpression of the Ext1 gene, which is crucial for cartilage growth and development. Additionally, the microspheres regulated immune responses, contributing to a reduction in OA symptoms. Conclusion: This study introduces an innovative therapeutic strategy for osteoarthritis using gelatin microspheres cultured with MSCs. By promoting Ext1 gene overexpression and regulating immune responses, these microspheres effectively mitigate OA symptoms. The findings highlight the potential of this biomaterial as a promising treatment option for OA.
研究领域:
医学
·
生物材料学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Han Yu,Huanhuan Luo,Jianping Chen,Xiaodong Hu,Yujiong Chen,Jiaqi Zhong,Botao Liu,Yanfang Liu,Gang Chen,Chenglong Huang,Zhaoxiang Peng
The utilization of stem cell biotechnology for osteoarthritis (OA) treatment is hindered by high operational costs, difficulties in maintaining stem cell viability, and limited efficacy of unguided stem cell differentiation. Magnesium ions (Mg 2+ ), crucial for tissue regeneration and repair, hold significant potential in OA treatment. However, further investigation is required to elucidate the precise mechanisms of Mg 2+ in OA treatment. Here, we investigated the optimal concentration of Mg 2+ to induce directed differentiation of stem cells and synthesized bioactive hydrogel microspheres (MDGM-Ps) capable of precisely releasing this concentration using microfluidic technology. Synthesized via polymerization of dopamine methacrylamide (DMA) and methacrylated gelatin (GelMA), these microspheres could chelate Mg 2+ and incorporate platelet-derived growth factor-BB into the hydrogel matrix for sustained release. In vitro , MDGM-Ps showed excellent biocompatibility and promoted stem cell recruitment. Importantly, Mg 2+ released from MDGM-Ps could guide stem cell differentiation through the PI3K-AKT pathway. Moreover, in vivo experiments suggested that MDGM-Ps could maintain the cartilage matrix and mitigate the progression of OA. In summary, MDGM-Ps not only harnessed the advantages of stem cell therapy, but also expanded the therapeutic applications of metal ions, thereby presenting a promising candidate for OA therapy.
研究领域:
生物技术
·
干细胞疗法
·
组织工程
·
骨科
·
再生医学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）