ACS Biomaterials Science & Engineering
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2018
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IF 4.432
Xupeng Mu,Jing Li,Shaohua Yan,Hongmei Zhang,Wenjing Zhang,Fuqiang Zhang,Jinlan Jiang
Biomimetic cell membrane coated nanoparticles (NPs) with desirable features have been extensively applied for various personalized biomedicine. However, there have not been relative explorations by employing the membrane nanocomplexes for small interfering RNA (siRNA) delivery. Herein, Fe3O4@PDA NPs with good photothermal capability were applied for efficient siRNA loading and delivery, which were then coated by mesenchymal stem cells (MSCs) to form a membrane. The data showed that MSCs membrane coated Fe3O4@PDA–siRNA NPs (Fe3O4@PDA–siRNA@MSCs) maintained the photothermal functionality and the capability of magnetic resonance imaging inherited from Fe3O4@PDA. The synthesized nanocomplexes exhibited excellent abilities in the delivery of siRNA into DU145 cells. Furthermore, Fe3O4@PDA–siRNA@MSCs NPs delivering siRNA against Plk1 gene could inhibit the expression of endogenous Plk1 gene and cause obvious apoptosis in DU145 cells. The synergistic combination of photothermal treatment and gene silencing showed obvious antitumor efficacy in a DU145 xenograft mice model. On the basis of preliminary in vitro and in vivo studies, Fe3O4@PDA–siRNA@MSCs NPs hold considerable promise as a carrier for gene and photothermal therapy.
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Acta Biomaterialia
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2016
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IF 6.008
Yifan Ma,Wenjing Zhang,Zihao Wang,Zi Wang,Qing Xie,Haoyi Niu,Han Guo,Yuan Yuan,Changsheng Liu
Calcium phosphate (CaP) scaffolds have been widely used as bone graft substitutes, but undesirable mechanical robustness and bioactivity greatly hamper its availability in clinic application. To address these issues, PEGylated poly (glycerol sebacate) (PEGS), a hydrophilic elastomer , was used to modify a model calcium phosphate cement (CPC) scaffold for bone regeneration in this study. The PEGS pre-polymer with PEG content from 0% to 40% was synthesized and was subsequently coated onto the pre-fabricated CPC scaffolds by facile infiltration and thermal-crosslink process. Compression strength and toughness of the CPC/PEGS composite scaffold (defined as CPX/Y, X referred to the PEG content in PEGS and Y referred to PEGS amount in final scaffold) were effectively tailored with increasing coating amount and PEG content, and CPX/Y exhibited an optimal compressive strength of 3.82 MPa and elongation at break of 13.20%, around 5-fold and 3-fold enhancement compared to the CPC. In vitro cell experiment with BMSCs as model indicated that coating and PEG-modified synchronously facilitated cell attachment and proliferation in a dose-dependent manner. Particularly, osteogenic differentiation of BMSCs on PEGS/CPC scaffold was strongly enhanced, especially for CP20/18. Further in vivo experiments confirmed that PEGS/CPC induced promoted osteogenesis in striking contrast to CPC and PGS/CPC. Collectively, hybrids scaffolds (around 18% coating amount and PEG content from 20% to 40%) with the combination of enhanced mechanical behavior and up-regulated cellular response were optimized and PEGS/CaP scaffolds can be deemed as a desirable option for bone tissue engineering. Statement of Significance Insufficient mechanical robustness and bioactivity still limit the availability of calcium phosphate (CaP) scaffolds in clinic application. Herein, calcium phosphate cement (CPC) scaffold, as a model CaP-matrix material, was modified with PEGylated PGS (PEGS) polymers by facile infiltration and thermal-crosslink process. Such biomimetic combination of PEGS and CaP-matrix porous scaffold was first explored, without affecting its porous structure. In this study, CPC scaffold was endowed with robust mechanical behavior and promoted bioactivity by simultaneously optimizing the amount of polymer-coating and the PEG content in PGS. In rat critical-sized calvarial defects repairing, osteogenic efficacy of PEGS/CPC further demonstrated the potential for application in bone tissue regeneration . The design concept proposed in this study might provide new insights into the development of future tissue engineering materials .
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BIOMATERIALS
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2020
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IF 10.317
Wenxi Zhou,Yu Zhou,Xinli Chen,Tingting Ning,Hongyi Chen,Qin Guo,Yiwen Zhang,Peixin Liu,Yujie Zhang,Chao Li,Yongchao Chu,Tao Sun,Chen Jiang
Immunotherapy has gained increasing focus in treating pancreatic ductal adenocarcinoma (PDAC), since conventional therapies like chemotherapy could not provide satisfactory improvement in overall survival outcome of PDAC patients. However, it is still not the game changing solution due to the unique tumor microenvironment and low cancer immunogenicity of PDAC. Thus, inducing more intratumoral effector immune cells as well as reversing immunosuppression is the core of PDAC treatment. Herein, we demonstrate an exosome-based dual delivery biosystem for enhancing PDAC immunotherapy as well as reversing tumor immunosuppression of M2-like tumor associated macrophages (M2-TAMs) upon disruption of galectin-9/dectin 1 axis. The deliver system is constructed from bone marrow mesenchymal stem cell (BM-MSC) exosomes, electroporation-loaded galectin-9 siRNA, and surficially modified with oxaliplatin (OXA) prodrug as an immunogenic cell death (ICD)-trigger. The use of biomaterials, BM-MSC exosomes, can significantly improve tumor targeting efficacy, thus increasing drug accumulation in the tumor site. The combined therapy (iEXO-OXA) elicits anti-tumor immunity through tumor-suppressive macrophage polarization, cytotoxic T lymphocytes recruitment and Tregs downregulation, and achieves significant therapeutic efficacy in cancer treatment.
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Reproductive Biology
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2023
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IF 2.1
Ganping Lai,Dan Bu,Maolin Chen,Hongfang Liu,Lei Dong
The present study aimed to identify the role of circPLOD2 in endometriosis and its underlying mechanisms. We determined circPLOD2 and miR-216a-5p expression in ectopic endometrial (EC) and eutopic endometrial (EU) samples as well as in endometrial samples from uterine fibroids of ectopic patients (EN) and embryonic stem cells (ESCs) using qRT-PCR. The association between circPLOD2 and miR-216a-5p or miR-216a-5p and zinc finger E-box binding homeobox 1 (ZEB1) expression was analyzed using Starbase, TargetScan, and dual-luciferase reporter gene assays. Cell viability , apoptosis , and migration and invasion were assessed using MTT, flow cytometry, and transwell assays, respectively. In addition, qRT-PCR and western blotting was used to measure circPLOD2, miR-216a-5p, E-cadherin, N-cadherin, and ZEB1 expression. circPLOD2 was upregulated and miR-216a-5p was downregulated in EC samples compared with that in EU samples. Similar trends were observed in ESCs. circPLOD2 interacted and negatively regulated miR-216a-5p expression in EC-ESCs. circPLOD2-siRNA significantly inhibited EC-ESC growth; promoted cellular apoptosis; and inhibited EC-ESC migration, invasion, and epithelial–mesenchymal transition; these effects could be reversed following miR-216a-5p inhibitor transfection. miR-216a-5p directly targeted and negatively regulated ZEB1 expression in EC-ESCs. In conclusion, circPLOD2 promotes the proliferation, migration, and invasion of EC-ESCs and inhibits their apoptosis by targeting miR-216a-5p. These findings indicate potential therapeutic targets for endometriosis.
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Materials Science & Engineering C-Materials for Biological Applications
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2021
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IF 7.328
Zongxi Wu,Shang Xie,Yifan Kang,Xiaofeng Shan,Qing Li,Zhigang Cai
Peripheral nerve injury can cause various degrees of damage to the morphological structure and physiological function of the peripheral nerve. At present, compared with “gold standard” autologous nerve transplantation, tissue engineering has certain potential for regeneration and growth; however, achieving oriented guidance is still a challenge. In this study, we used 3D bioprinting to construct a nerve scaffold of RSC96 cells wrapped in sodium alginate/gelatin methacrylate (GelMA)/bacterial nanocellulose (BNC) hydrogel. The 5% sodium alginate+5% GelMA+0.3% BNC group had the thinnest lines among all groups after printing, indicating that the inherent shape of the scaffold could be maintained after adding BNC. Physical and chemical property testing (Fourier transform infrared, rheometer, conductivity, and compression modulus) showed that the 5% alginate+5% GelMA+0.3% BNC group had better mechanical and rheological properties. Live/dead cell staining showed that no mass cell death was observed on days 1, 3, 5, and 7 after printing. In the 5% alginate+5% GelMA group, the cells grew and formed linear connections in the scaffold. This phenomenon was more obvious in the 5% alginate+5% GelMA+0.3% BNC group. In the 5% alginate+5% GelMA+0.3% BNC group, S-100β immunofluorescence staining and cytoskeleton staining showed oriented growth. Polymerase chain reaction (PCR) array results showed that mRNA levels of related neurofactors ASCL1, POU3F3, NEUROG1, DLL1, NOTCH1 and ERBB2 in the 5%GelMA+0.3%BNC group were higher than those of other groups. Four weeks after implantation in nude mice, RSC96 cells grew and proliferated well, blood vessels grew, and S-100β immunofluorescence was positive. These results indicate that a 3D-bioprinted sodium alginate/GelMA/BNC composite scaffold can improve cell-oriented growth, adhesion and the expression of related factors. This 3D-bioprinted composite scaffold has good biocompatibility and is expected to become a new type of scaffold material in the field of neural tissue engineering.
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Nature Communications
·
2023
·Vol. 14
·期 1
·1-15
·
IF 16.6
He Ning,Wang Xiaonan,Shi Liyang,Li Jing,Mo Lan,Chen Feng,Huang Yuting,Liu Hairong,Zhu Xiaolong,Zhu Wei,Mao Yiqi,Han Xiaoxiao
Light-based 3D bioprinting is now employed widely to fabricate geometrically complex constructs for various biomedical applications. However, the inherent light scattering defect creates significant challenges in patterning dilute hydrogels to form high-fidelity structures with fine-scale features. Herein, we introduce a photoinhibiting approach that can effectively suppress the light scattering effect via a mechanism of simultaneous photoabsorption and free-radical reaction. This biocompatible approach significantly improves the printing resolution (~1.2 - ~2.1 pixels depending on swelling) and shape fidelity (geometric error less than 5%), while minimising the costly trial-and-error procedures. The capability in patterning 3D complex constructs using different hydrogels is demonstrated by manufacturing various scaffolds featuring intricate multi-sized channels and thin-walled networks. Importantly, cellularised gyroid scaffolds (HepG2) are fabricated successfully, exhibiting high cell proliferation and functionality. The strategy established in this study promotes the printability and operability of light-based 3D bioprinting systems, allowing numerous new applications for tissue engineering.
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Brain Sciences
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2022
·Vol. 12
·期 12
·1620
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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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Gastroenterology Research and Practice
·
2021
·
IF 2.26
Li Liu,Min Yang,Wenxiao Dong,Tianyu Liu,Xueli Song,Yu Gu,Sinan Wang,Yi Liu,Zaripa Abla,Xiaoming Qiao,Wentian Liu,Kui Jiang,Bangmao Wang,Jie Zhang,Hailong Cao
Background. Patients with prolonged inflammatory bowel disease (IBD) can develop into colorectal cancer (CRC), also called colitis-associated cancer (CAC). Studies have shown the association between gut dysbiosis, abnormal bile acid metabolism, and inflammation process. Here, we aimed to investigate these two factors in the CAC model. Methods. C57BL/6 mice were randomly allocated to two groups: azoxymethane/dextran sodium sulfate (AOM/DSS) and control. The AOM/DSS group received AOM injection followed by DSS drinking water. Intestinal inflammation, mucosal barrier, and bile acid receptors were determined by real-time PCR and immunohistochemistry. Fecal microbiome and bile acids were detected via 16S rRNA sequencing and liquid chromatography-mass spectrometry. Results. The AOM/DSS group exhibited severe mucosal barrier impairment, inflammatory response, and tumor formation. In the CAC model, the richness and biodiversity of gut microbiota were decreased, along with significant alteration of composition. The abundance of pathogens was increased, while the short-chain fatty acids producing bacteria were reduced. Interestingly, Clostridium XlV and Lactobacillus, which might be involved in the bile acid deconjugation, transformation, and desulfation, were significantly decreased. Accordingly, fecal bile acids were decreased, accompanied by reduced transformation of primary to secondary bile acids. Given bile acid receptors, the ileum farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) axis was downregulated, while Takeda G-protein receptor 5 (TGR5) was overexpressed in colonic tumor tissues. Conclusion. Gut dysbiosis might alter the metabolism of bile acids and promote CAC, which would provide a potential preventive strategy of CAC by regulating gut microbiota and bile acid metabolism.
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Oxidative Medicine and Cellular Longevity
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2022
·
IF 7.31
Fei Jia,Yu Liu,Xinyu Dou,Chuanchao Du,Tianli Mao,Xiaoguang Liu
Osteosarcoma (OS) is the most common malignancy of bone. Liensinine exerts antitumor effects on cancers of the colon, breast, and gallbladder. However, its antitumor activity in OS remains unclear. This study is aimed at investigating the efficacy of liensinine against OS and the underlying mechanism of action. Cell proliferation, apoptosis, and cycle arrest in OS were detected using the Cell Counting Kit-8 (CCK-8), colony formation, and flow cytometry assays, respectively. The production of reactive oxygen species (ROS), glutathione (GSH) and glutathione disulfide (GSSG) concentrations, and mitochondrial membrane potential (MMP) of OS cells were measured by flow cytometry, colorimetry, and JC-1 staining. The expressions of factors related to apoptosis, cell cycle, and activation of the JAK2/STAT3 pathway were determined by Western blotting. To examine the potential role of ROS, an antioxidant (N-acetyl cysteine, NAC) was used in combination with liensinine. In vivo, we generated a xenograft mouse model to assess its antitumor efficacy. Tissue level expressions of factors related to apoptosis and activation of the JAK2/STAT3 pathway were assessed by immunohistochemistry or Western blotting. Liensinine inhibited the proliferation and induced G0/G1 phase arrest and apoptosis of OS cells in a dose-dependent manner. Additionally, liensinine promoted intracellular ROS production, enhanced the GSSG/GSH ratio, and induced MMP loss and ROS-mediated suppression of the JAK2/STAT3 pathway. NAC significantly attenuated the liensinine-induced antitumor activities and activated the JAK2/STAT3 pathway. In vivo, liensinine effectively inhibited the OS growth and promoted apoptosis; however, it had no negative effect on the internal organs. In conclusion, liensinine-induced ROS production could suppress the activation of the JAK2/STAT3 pathway and inhibit the OS growth both in vivo and in vitro. Our findings provided a new rationale for subsequent academic and clinical research on OS treatment.
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RSC Advances
·
2019
·Vol. 9
·期 15
·8315-8325
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IF 3.049
Zhiping Qi,Wenlai Guo,Shuang Zheng,Chuan Fu,Yue Ma,Su Pan,Qinyi Liu,Xiaoyu Yang
The mammalian central nervous system has a limited ability for self-repair under injury conditions. The treatment of nerve injuries has been revolutionised with the development of tissue engineering techniques. However, the lack of bioactivity has severely restricted the application of biodegradable implants for neurogenesis. Therefore, surface modification of biomaterials is crucial to improve their bioactivity and promote endogenous repair mechanisms for nerve regeneration. Insulin-like growth factor 1 (IGF-1) is a growth factor for neuroprotection and neurogenesis. In this study, IGF-1 was successfully immobilised on graphene oxide (GO)-incorporated poly(lactic-co-glycolic acid) (PLGA) biodegradable electrospun nanofibres. For the in vitro investigation, neural stem cells (NSCs) were cultured on different nanofibres to observe various cellular activities. GO enhanced NSC survival under H2O2 pre-treatment and neuronal differentiation to some extent. More importantly, the immobilisation of IGF-1 onto the PLGA/GO nanofibres resulted in significantly increased NSC survival, proliferation, and differentiation. Findings from this study revealed that using PLGA/GO electrospun nanofibres to immobilise IGF-1 has excellent potential for the enhancement of the neuroprotective and neurogenic effects of nerve implants.
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Applied Bionics and Biomechanics
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2020
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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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Advanced Healthcare Materials
·
2022
·Vol. 11
·期 12
·2102807
·
IF 11.092
Yuzhou Li,Yiru Fu,He Zhang,Xu Wang,Tao Chen,Yanqiu Wu,Xinxin Xu,Sheng Yang,Ping Ji,Jinlin Song
Bone defects have been increasingly prevalent around the globe and traditional bone substitutes are constantly limited by low abundance and biosafety due to their animal-based resources. Plant-based scaffolds are currently studied as a green candidate but the bioinertia of cellulose to mammalian cells leads to uncertain bone regeneration. Inspired by the cross-kingdom adhesion of plants and bacteria, this work proposes a concept of a novel plant bone substitute, involving coating decellularized plant with nano amyloids and nano hydroxyapatites, to bridge the plant scaffold and animal tissue regeneration. Natural microporosity of plants can guide alignment of mammalian cells into various organ-like structures. Taking advantage of the bioactive nano amyloids, the scaffolds drastically promote cell adhesion, viability, and proliferation. The enhanced bio-affinity is elucidated as positively charged nano amyloids and serum deposition on the nanostructure. Nano-hydroxyapatite crystals deposited on amyloid further prompt osteogenic differentiation of pre-osteoblasts. In vivo experiments prove successful trabeculae regeneration in the scaffold. Such a hierarchical design leverages the dedicated microstructure of natural plants and high bioactivity of nano amyloid/hydroxyapatite coatings, and addresses the abundant resource of bone substitutes. Not limited to their current application, plant materials functionalized with nano amyloid/hydroxyapatite coatings allow many cross-kingdom tissue engineering and biomedical applications.
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