CELLULOSE
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2023
·Vol. 30
·期 9
·5607-5622
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IF 5.7
Zhang Kecan,Li Jing,He Liang,Zhou Huajing,Guan Qingqing,Chen Keli,Shan Shaoyun,Hu Tianding
Cellulose nano/microfibres (CNFs/CMFs) with high aspect ratio were essential for mechanical strength and flexibility properties. In this study, the tobacco stem was employed as raw material for delignification with soda-oxygen (SO). By comparison with the caustic soda-anthraquinone (SAQ) treatment, based on process performance including pulp yield, residual lignin and fibre characteristics, the two-stage delignification process with total alkali 15% was selected for further preparing CNFs/CMFs with ultrasonication. Results showed that the aspect ratio of highly homogeneous CNFs/CMFs could achieve as ultra-high as 17,645. FTIR and XRD results showed that hemicellulose and lignin in CNFs/CMFs were widely removed, and the crystallinity was about 62%. TGA results exhibited that the degradation temperature was significantly enhanced to 330.2 °C. Finally, the CNF/CMF-based film was prepared and its folding endurance, tensile breaking strength, and burst strength could achieve 136, 61.28 N m/g, 278 kPa m 2 /g. The production of CNFs/CMFs from underutilized tobacco stems provided the potential to add value for industrial waste.
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MATERIALS & DESIGN
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2023
·
IF 8.4
Shengqi Zang,Can Xiao,Maodian He,Bo Chen,Bingyao Liu,Shuai Yi,Lei Wang,Junxia Li,Xiaolei Shi,Shoushan Bu,Lei Jin
Biomimetic surface modification of scaffolds with osteoinductive molecules is a promising strategy for improving the bioactivity of scaffold and stimulating stem cell signals in bone tissue engineering. Zirconia (ZrO 2 ) offers excellent mechanical properties and biocompatibility, but its bio-inert nature hinders its use in bone regeneration applications. Recombinant human bone morphogenetic protein 7 (rhBMP-7) and arginine-glycine-aspartate (RGD) peptide were investigated for their potential use as surface-modifying biomolecules on the ZrO 2 scaffold. Our results showed that human dental pulp stem cells (hDPSCs) were induced to osteogenic differentiation by rhBMP-7 and RGD in a dose-dependent manner. Significantly enhanced alkaline phosphatase activity and up-regulated expression of osteogenic genes in hDPSCs were associated with rhBMP-7 and RGD grafting onto the ZrO 2 scaffold. Western blot analysis revealed that rhBMP-7 and RGD grafting led to activation of the SMAD1/5, p38 MARK, and ERK signaling pathways during hDPSCs differentiation. After 4 and 8 weeks of transplantation, the hDPSCs-seeded ZrO 2 -RGD-BMP-7 scaffold facilitated osteogenic differentiation and enhanced in vivo bone formation in critical-sized calvarial bone defects. The results support the simultaneous use of rhBMP-7 and RGD as surface-modifying biomolecules and hDPSCs as a source of osteogenic stem cells in conjugation with ZrO 2 -based porous scaffold for bone tissue engineering.
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BIOMEDICINE & PHARMACOTHERAPY
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2023
·
IF 7.5
Zhenzhen Zhang,Lingling Yang,Ya Li,Di Sun,Rong Chen,Shengqian Dou,Ting Liu,Sai Zhang,Qingjun Zhou,Lixin Xie
Diabetic keratopathy (DK), the diabetic complication in the cornea, is characterized by the delayed epithelial regeneration and sensory nerve degeneration. The involvement of limbal stem/progenitor cells (LSPCs) dysfunction has been reported, however the pathogenic mechanisms remain unclear. Here, we confirmed the dysfunction of LSPCs in diabetic mouse and human corneas. The sympathetic nerve in the cornea was adjacent to LSPCs, and the sympathetic overactivation was found in diabetic mice. Surgical and pharmacological ablation of sympathetic nerves rescued the LSPCs function and promoted corneal epithelial regeneration in diabetic mice. In contrast, both topical norepinephrine (NE) application and chemogenetic sympathetic overactivation directly impaired the stemness and proliferation characteristics of LSPCs, as well as the normal epithelial regeneration. Moreover, we identified that β2-adrenoceptor ( Adrb2 ) was the predominant adrenergic receptor expressed in LSPCs by corneal limbal single-cell sequencing and real time PCR (RT-PCR) analysis of sorted LSPCs. The Adrb2 knockout mice exhibited the enhancement of epithelial regeneration and LSPCs function, compared with the wild-type mice. Similarly, topical application of the Adrb2 specific antagonist ICI 118, 551 effectively accelerated diabetic corneal epithelial regeneration with the restored LSPCs function. Mechanistically, sonic hedgehog (Shh) activity mediated the downstream effects of NE-Adrb2 signaling pathway in regulating LSPCs and epithelial regeneration. Taken together, our data revealed the involvement of sympathetic overactivation in the impairment of diabetic LSPCs function and corneal epithelial regeneration through the NE-Adrb2-Shh signaling pathway. The interference of sympathetic overactivation may provide novel treatment strategies for diabetic keratopathy.
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Current Medical Science
·
2023
·Vol. 43
·期 2
·223-231
·
IF 2.4
Zhang Qing,Pan Rong-rong,Wu Yu-tao,Wei Yu-miao
Objective Vascular smooth muscle cell (VSMC) differentiation from stem cells is one source of the increasing number of VSMCs that are involved in vascular remodeling-related diseases such as hypertension, atherosclerosis, and restenosis. MicroRNA-146a (miR-146a) has been proven to be involved in cell proliferation, migration, and tumor metabolism. However, little is known about the functional role of miR-146a in VSMC differentiation from embryonic stem cells (ESCs). This study aimed to determine the role of miR-146a in VSMC differentiation from ESCs. Methods Mouse ESCs were differentiated into VSMCs, and the cell extracts were analyzed by Western blotting and RT-qPCR. In addition, luciferase reporter assays using ESCs transfected with miR-146a/mimic and plasmids were performed. Finally, C57BL/6J female mice were injected with mimic or miR-146a-overexpressing ESCs, and immunohistochemistry, Western blotting, and RT-qPCR assays were carried out on tissue samples from these mice. Results miR-146a was significantly upregulated during VSMC differentiation, accompanied with the VSMC-specific marker genes smooth muscle-alpha-actin (SMαA), smooth muscle 22 (SM22), smooth muscle myosin heavy chain (SMMHC), and h1-calponin. Furthermore, overexpression of miR-146a enhanced the differentiation process in vitro and in vivo . Concurrently, the expression of Kruppel-like factor 4 (KLF4), predicted as one of the top targets of miR-146a, was sharply decreased in miR-146a-overexpressing ESCs. Importantly, inhibiting KLF4 expression enhanced the VSMC-specific gene expression induced by miR-146a overexpression in differentiating ESCs. In addition, miR-146a upregulated the mRNA expression levels and transcriptional activity of VSMC differentiation-related transcription factors, including serum response factor (SRF) and myocyte enhancer factor 2c (MEF-2c). Conclusion Our data support that miR-146a promotes ESC-VSMC differentiation through regulating KLF4 and modulating the transcription factor activity of VSMCs.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Hongxia Xie,Ge Shi,Ruizi Wang,Qianqian Chen,Aixi Yu,Ang Lu
Uncontrollable hemorrhage from deep noncompressible wounds remains an intractable challenge. Herein, inspired by the euryale ferox stem which is capable of transporting water and nutrient substances efficiently along longitudinally aligned channels, an anisotropic sponge with rapidly liquid absorption capacity, excellent mechanical compressibility and antibacterial property based on quaternized cellulose (QC), xanthan gum (XG) and reduced graphene oxide (rGO), was constructed. The euryale ferox stem-like structure and multiple interactions, involving hydrogen bonding, electrostatic interaction and chemical crosslinking, endowed the sponge with excellent fatigue resistance, elasticity and efficient liquid absorption capacity. In vivo rat liver injury, tail amputation and liver noncompressible hemorrhage model experiments confirmed that the sponge exhibited superior hemostatic performance than commercial gelatin sponge, attributing to the positive charge, efficient absorption capacity and rough surface of the sponge, which synergistically promoting the aggregation and activation of red blood cells and platelets as well as formation of fibrin network, leading to accelerated blood coagulation process. Besides, the sponge showed favorable cytocompatibility, hemocompatibility and antibacterial property. Overall, the bioinspired sponge had fantastic potential for controlling deep noncompressible hemorrhage and providing a new idea for designing hemostatic materials.
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Materials Today Bio
·
2023
·
IF 8.2
Tiange Chen,Yuguo Xia,Liyang Zhang,Tao Xu,Yan Yi,Jianwei Chen,Ziyuan Liu,Liting Yang,Siming Chen,Xiaoxi Zhou,Xin Chen,Haiyu Wu,Jinfang Liu
Neural stem cell (NSC) has gained considerable attention in traumatic brain injury (TBI) treatment because of their ability to replenish dysfunctional neurons and stimulate endogenous neurorestorative processes. However, their therapeutic effects are hindered by the low cell retention rate after transplantation into the dynamic brain. In this study, we found cerebrospinal fluid (CSF) flow after TBI is an important factor associated with cell loss following NSC transplantation. Recently, several studies have shown that hydrogels could serve as a beneficial carrier for stem cell transplantation, which provides a solution to prevent CSF flow-induced cell loss after TBI. For this purpose, we evaluated three different hydrogel scaffolds and found the gelatin methacrylate (GelMA)/sodium alginate (Alg) (GelMA/Alg) hydrogel scaffold showed the best capabilities for NSC adherence, growth, and differentiation. Additionally, we detected that pre-differentiated NSCs, which were loaded on the GelMA/Alg hydrogel and cultured for 7 days in neuronal differentiation medium (NSC [7d]), had the highest cell retention rate after CSF impact. Next, the neuroprotective effects of the NSC-loaded GelMA/Alg hydrogel scaffold were evaluated in a rat model of TBI. NSC [7d]-loaded GelMA/Alg markedly decreased microglial activation and neuronal death in the acute phase, reduced tissue loss, alleviated astrogliosis, promoted neurogenesis, and improved neurological recovery in the chronic phase. In summary, we demonstrated that the integration with the GelMA/Alg and modification of NSC differentiation could inhibit the influence of CSF flow on transplanted NSCs, leading to increased number of retained NSCs and improved neuroprotective effects, providing a promising alternative for TBI treatment.
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JOURNAL OF CONTROLLED RELEASE
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2023
·
IF 10.8
Yinjuan Lv,Chenggong Yu,Xiaodi Li,Hongying Bao,Shaoshuai Song,Xiaoling Cao,Haixia Lin,Jie Huang,Zhijun Zhang
Mesenchymal stem cell (MSC) transplantation is emerging as a promising approach in the treatment of idiopathic pulmonary fibrosis (IPF), while it is still impeded by several challenges, including unsatisfactory treatment outcomes due to the poor survival of transplanted MSCs, and the lack of non-invasive and long-term imaging modality for tracking the behavior of MSCs. Herein, copper-based nanozyme (Cu x O NPs) and gold nanoparticles (Au NPs) were encapsulated in oxidation-sensitive dextran (Oxi-Dex), a dextran derivative with reactive oxygen species (ROS)-responsiveness, forming a kind of novel nanocomposites (assigned as RSNPs) to act as ROS scavengers and computer tomography (CT) imaging tracers. After being internalized by MSCs, RSNPs enabled continuous CT imaging tracking of the transplanted MSCs for 21 days in IPF treatment, obtaining the location and distribution of the transplanted MSCs. Once MSCs were attacked by oxidative stress, the intracellular RSNPs could activate ROS clearance on demand by releasing Cu x O NPs, thereby enhancing the therapeutic efficacy against IPF by improving cell survival. Taken together, a novel multifunctional RSNP was fabricated to label MSCs for CT imaging tracking and clearing superfluous ROS, presenting a promising high-efficient IPF therapy.
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Bioactive Materials
·
2023
·
IF 18.9
Qiji Lu,Jingjing Diao,Yingqu Wang,Jianlang Feng,Fansen Zeng,Yan Yang,Yudi Kuang,Naru Zhao,Yingjun Wang
Bone bionics and structural engineering have sparked a broad interest in optimizing artificial scaffolds for better bone regeneration. However, the mechanism behind scaffold pore morphology-regulated bone regeneration remains unclear, making the structure design of scaffolds for bone repair challenging. To address this issue, we have carefully assessed diverse cell behaviors of bone mesenchymal stem cells (BMSCs) on the β-tricalcium phosphate (β-TCP) scaffolds with three representative pore morphologies (i.e., cross column, diamond, and gyroid pore unit, respectively). Among the scaffolds, BMSCs on the β-TCP scaffold with diamond pore unit (designated as D-scaffold) demonstrated enhanced cytoskeletal forces, elongated nucleus, faster cell mobility, and better osteogenic differentiation potential (for example, the alkaline phosphatase expression level in D-scaffold were 1.5–2 times higher than other groups). RNA-sequencing analysis and signaling pathway intervention revealed that Ras homolog gene family A (RhoA)/Rho-associated kinase-2 (ROCK2) has in-depth participated in the pore morphology-mediated BMSCs behaviors, indicating an important role of mechanical signaling transduction in scaffold-cell interactions. Finally, femoral condyle defect repair results showed that D-scaffold could effectively promote endogenous bone regeneration, of which the osteogenesis rate was 1.2–1.8 times higher than the other groups. Overall, this work provides insights into pore morphology-mediated bone regeneration mechanisms for developing novel bioadaptive scaffold designs.
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International Journal of Nanomedicine
·
2023
·
IF 8
Yongai Xiong,Tingting Chen,Lei Chen,Rongshan Cai
Introduction Radiotherapy and chemotherapy are the fundamental causes of myelosuppression in cancer patients, which usually induce a serious hematopoietic system toxicity, causing the hemocytes and immunity decline of patients. Ziyuglycoside I (ZgI), an active ingredient isolated from traditional Chinese medicine Sanguisorba officinalis L, has been demonstrated to increase the leucocytes and protect hematopoietic stem cells, which is related to its promotion of autophagy in hematopoietic stem cells.Methods In the present study, we formulated the SH-PEG-NH2-coated gold nanoparticles loading ZgI (ZgI-AuNPs) with a enhanced autophagy promotion in hematopoietic stem cells. ZgI-AuNPs were prepared by HAuCl4-sodium citrate reduction method, and the synthesis of ZgI-AuNPs was validated by XRD, FT-IR, DSC, and TEM findings. Furthermore, the drug loading rate and the release of ZgI were evaluated, and the ZgI-AuNPs’ effects on autophagy and immunofluorescence staining for LC3B were tested. Finally, the effect of ZgI-AuNPs on the autophagy and hematopoietic ability of HSCs in vivo was also carried out.Results The prepared ZgI-AuNPs have an irregular cubic crystal structure by TEM observation, and the average particle size was 340 ± 16.5 nm determined by DLS. The XRD, FT-IR and DSC detection showed that the ZgI had been well loaded in AuNPs, and the AuNPs can load the ZgI at a content of 160.63 ± 1.35 μg·mg−1. Meanwhile, the AuNPs can reduce the drug release rate of ZgI. Importantly, the ZgI-AuNPs enhanced autophagy of HSCs both in vitro and in vivo. At the same time, the gold nanoparticles enhance the hematopoietic effect of ZgI on mice HSCs.Conclusion Our research suggests that SH-PEG-NH2-coated gold nanoparticles loading ZgI has potential application in myelosuppression therapy.
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DRUG DELIVERY
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2023
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IF 6
Xiaoyan Xu,Tianhao Zhou,Xudong Wei,Xuelian Jiang,Jiyan Cao
Although surgery-based comprehensive therapy is becoming the main approach to treat laryngeal cancer, recurrence, metastasis, radiotherapy resistance and chemotherapy tolerance are still the main causes of death in patients. Targeted inhibition of laryngeal cancer stem cells has been considered as the consensus to cure laryngeal cancer. Our previous study has confirmed proto-oncogene Bmi-1 as a key regulator for self-renewal of laryngeal cancer stem cells. Targeted knockdown of Bmi-1 gene effectively inhibited the self-renewal and differentiation of laryngeal cancer stem cells, leading to the promoted sensitivity to chemotherapy including paclitaxel. However, due to off-target effects and quick degradation of the naked Bmi-1-RNAi small RNA oligo by nuclease in body fluids, it is urgently needed to develop a tumor-targeted delivery system with a protective shell. In this study, we designed and synthesized cRGD peptide-modified chitosan-polyethylene glycol slow-release nanoparticles (mPEG-CS-cRGD/Bmi-1RNAi-PTX) containing Bmi-1RNAi siRNA oligo and paclitaxel, which showed spherical in shape, 200 nm diameter in size, low cytotoxicity, strong DNA wrapping, resistance to nuclease degradation and high transfection efficiency to cells. Functional analysis indicated significant suppression of cell proliferation and migration and induction of apoptosis by the nanocomplex in laryngeal cancer cells in vitro. By application to the mouse model with laryngeal cancer, the nanocomplex inhibited tumor growth significantly in vivo. In addition, cRGD peptide, paclitaxel and Bmi-1 siRNA in the nanoparticles showed synergistic effects to suppress laryngeal cancer stem cells. In conclusion, this study not only developed a laryngeal tumor-targeted chemotherapeutic system, but also demonstrated a Bmi-1 RNAi-based chemotherapeutic strategy to inhibit cancer stem cells, having strong potential to treat laryngeal cancer patients suffering therapy resistance and/or tumor recurrence.
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GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
·
2022
·Vol. 261
·期 3
·723-734
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IF 3.535
Zhou Jin,Ding Yuanyuan,Zhang Yongqiang,Zheng Dehui,Yan Lifeng,Guo Mengxiang,Mao Yani,Yang Lihong
Purpose This study was aimed at exploring the function of Exosomes isolated from bone marrow-derived mesenchymal stem cells (BMSC-Exos) in corneal wound healing and at revealing the underlying mechanisms involving the p44/42 mitogen-activated protein kinase (MAPK) pathway. Methods The isolated BMSC-Exos were identified by transmission electron microscopy, Western blot, and nanoparticle tracking analysis. After coculture with BMSC-Exos, the proliferation and migration of human corneal epithelial cells (HCEs) were evaluated. The protein expression of p-MEK/MEK and p44/42 MAPK was detected by Western blot. A mouse model of alkali-burned cornea was established via NaOH exposure. After injection with BMSC-Exos, the pathological changes and expression of α-SMA (a fibrosis marker) and CD31 (a vascularization marker) in corneal tissues were detected. Results BMSC-Exos enhanced the proliferation and migration of HCEs in a dose-dependent manner. The p44/42 MAPK pathway was activated by the treatment of BMSC-Exos, and its blocking using U0126 partially abrogated the effects of BMSC-Exos on promoting the proliferation and migration of HCEs. In vivo , the injection of BMSC-Exos facilitated the remission of the pathological changes (inflammation) and weakened the upregulation of α-SMA (fibrosis) and CD31 (vascularization) in corneal tissues of mice with alkali-burn injury. Conclusion BMSC-Exos promoted the proliferation and migration of HCEs via activating the p44/42 MAPK pathway in vitro and also inhibited alkali burn-induced inflammation, fibrosis, and vascularization in corneal tissues in vivo . BMSC-Exos may be promising resources for promoting corneal wound healing.
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RSC Advances
·
2019
·Vol. 9
·期 21
·12010-12019
·
IF 3.049
Meihua Xie,ShuLin Luo,Ying Li,Laiya Lu,Cuijun Deng,Yu Cheng,Feng Yin
Adipose-derived stem cells (ADSCs) hold great potential in cartilage tissue engineering due to their multipotency and ease of availability. MRI is an effective and noninvasive imaging approach to track cells and observe new tissue regeneration. It is essential to find a compatible and efficient imaging reagent without affecting the stemness of ADSCs. Herein, we developed chitosan-modified iron oxide nanoparticles (IO-CS) as the T2 contrast reagent with good cell compatibility and high cellular uptake efficiency and used IO-CS for ADSC intra-articular imaging in a rat osteoarthritis (OA) model. TEM demonstrated the great morphology and size distribution of IO-CS nanoparticles with the size of 17 nm. Magnetization (29.4 emu per g) and MRI tests confirmed (R2 of 184 mM−1 s−1) the feasibility of IO-CS nanoparticles as an MRI contrast reagent. In addition, the IO-CS nanoparticles showed good cellular compatibility and high labeling efficiency as compared to the commercial agent ferumoxytol. Moreover, incorporation of IO-CS nanoparticles did not alter the adipogenic, osteogenic and chondrogenic differentiation ability of ADSCs. Furthermore, the MRI transverse R2 maps showed a persistence time of the IO-CS nanoparticles in ADSCs of 6 days in vitro. Then, we investigated the imaging capability of the IO-CS nanoparticle-labeled ADSCs in vivo with MRI for 5 weeks. The histological studies demonstrated the intra-articular biodistribution of the IO-CS nanoparticles, including in the cartilage superficial layer, synovial sublining layer, periosteum and bone marrow cavity. They provided systemic distribution information of the ADSCs in the OA rat model. In summary, we developed an accessible and effective T2 imaging reagent with good biocompatibility and maintenance of the stemness of ADSCs. This showed the potential translational application of IO-CS nanoparticles as an MRI reagent in cartilage tissue engineering.
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