BIOMATERIALS
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2023
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IF 14
Yenan Wu,Haiwei Liang,Aiping Luo,Yong Li,Zhiqiang Liu,Xin Li,Wenxin Li,Kaini Liang,Junyang Li,Zhihua Liu,Yanan Du
Cancer stem cells (CSCs) are crucial for tumorigenesis, metastasis, and therapy resistance in esophageal squamous cell carcinoma (ESCC). To further elucidate the mechanism underlying characteristics of CSCs and develop CSCs-targeted therapy, an efficient culture system that could expand and maintain CSCs is needed. CSCs reside in a complex tumor microenvironment , and three-dimensional (3D) culture systems of biomimetic scaffolds are expected to better support the growth of CSCs by recapitulating the biophysical properties of the extracellular matrix (ECM). Here, we established gelatin-based 3D biomimetic scaffolds mimicking the stiffness and collagen content of ESCC, which could enrich ESCC CSCs efficiently. Biological changes of ESCC cells laden in scaffolds with three different viscoelasticity emulating physiological stiffness of esophageal tissues were thoroughly investigated in varied aspects such as cell morphology , viability, cell phenotype markers , and transcriptomic profiling. The results demonstrated the priming effects of viscoelasticity on the stemness of ESCC. The highly viscous scaffolds (G’: 6–403 Pa; G’’: 2–75 Pa) better supported the enrichment of ESCC CSCs, and the TGF-beta signaling pathway might be involved in regulating the stemness of ESCC cells. Compared to two-dimensional (2D) cultures, highly viscous scaffolds significantly promoted the clonal expansion of ESCC cells in vitro and tumor formation ability in vivo . Our findings highlight the crucial role of biomaterials’ viscoelasticity for the 3D culture of ESCC CSCs in vitro , and this newly-established culture system represents a valuable platform to support their growth, which could facilitate the CSCs-targeted therapy in the future.
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高影响因子
Biomaterials Advances
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2023
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IF 0
Guodong Liu,Mengjiao Ma,Huiyi Yang,Wei He,Yajie Xie,Junfei Li,Jiaping Li,Feilong Zhao,Yudong Zheng
Natural polymers and minerals can be combined to simulate natural bone for repairing bone defects. However, bone defects are often irregular and pose challenges for their repair. To overcome these challenges, we prepared Chitosan/Polydopamine/Octacalcium phosphate (CS/PDA/OCP) microcarriers that mimic bone composition and micro-size to adapt to different bone defect defects. CS/PDA microspheres were prepared by emulsion phase separation method and PDA in-situ polymerization. Finally, it was used to adsorb and immobilize OCP particles, resulting in the preparation of CS/PDA/OCP composite microcarriers. The microcarriers maintain an interconnected porous structure and appropriate porosity, which promotes cell adhesion, proliferation, and nutrient exchange. Subsequently, the protein adsorption capacity, simulated degradation, cell adhesion and proliferation capacity of the composite microcarriers were investigated. Additionally, their ability to simulate mineralization and induce osteogenic differentiation of BMSCs was characterized. The results demonstrated that the composite microcarrier had good biocompatibility and was conducive to cell adhesion and proliferation. Moreover, ALP and ARS staining revealed that the addition of OCP significantly enhanced the osteogenic differentiation of BMSCs. These results indicate that the composite microcarrier has promising prospects for bone repair applications.
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Asian Journal of Pharmaceutical Sciences
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2023
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IF 10.2
Shan Gao,Meng Liu,Dongzhu Liu,Xinru Kong,Yuelin Fang,Yingying Li,Hang Wu,Jianbo Ji,Xiaoye Yang,Guangxi Zhai
Growing evidence suggests that the presence of cancer stem cells (CSCs) is a major challenge in current tumor treatments, especially the transition from non-CSCs to differentiation of CSCs for evading conventional therapies and driving metastasis. Here we propose a therapeutic strategy of synergistic differentiation therapy and phototherapy to induce differentiation of CSCs into mature tumor cells by differentiation inducers and synergistic elimination of them and normal cancer cells through phototherapy. In this work, we synthesized a biomimetic nanoplatform loaded with IR-780 and all-trans retinoic acid (ATRA) via biomineralization. This method can integrate aluminum ions into small-sized protein carriers to form nanoclusters, which undergo responsive degradation under acidic conditions and facilitate deep tumor penetration. With the help of CSC differentiation induced by ATRA, IR-780 inhibited the self-renewal of CSCs and cancer progression by generating hyperthermia and reactive oxygen species in a synergistic manner. Furthermore, ATRA can boost immunogenic cell death induced by phototherapy, thereby strongly causing a systemic anti-tumor immune response and efficiently eliminating CSCs and tumor cells. Taken together, this dual strategy represents a new paradigm of targeted eradication of CSCs and tumors by inducing CSC differentiation, improving photothermal therapy/photodynamic therapy and enhancing antitumor immunity.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2017
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IF 3.649
Tian-Yuan Zhang,Jia-He Wu,Qian-Hao Xu,Xia-Rong Wang,Jingxiong Lu,Ying Hu,Jun-ichiro Jo,Masaya Yamamoto,Daishun Ling,Yasuhiko Tabata,Jian-Qing Gao
Gene engineered mesenchymal stem cells (MSCs) have been proposed as promising tools for their various applications in biomedicine. Nevertheless, the lack of an effective and safe way to genetically modify these stem cells is still a major obstacle in the current studies. Herein, we designed novel magnetic complexes by assembling cationized pullulan derivatives with magnetic iron oxide nanoparticles for delivering target genes to MSCs. Results showed that this complexes achieved effective gene expression with the assistance of external magnetic field, and resisted the adverse effect induced by serum proteins on the gene delivery. Moreover, neither significant cytotoxicity nor the interference on the osteogenic differentiation to MSCs were observed after magnetofection. Further studies revealed that this effective and serum resistant gene transfection was partly due to the accelerated and enhanced intracellular uptake process driven by external magnetic field. To conclude, the current study presented a novel option for genetic modification of MSCs in an effective, relatively safe and serum compatible way.
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高影响因子
Journal of Cosmetic Dermatology
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2023
·Vol. 22
·期 5
·1670-1679
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IF 2.3
Wei Sheng,Qi Song,XiangZheng Su,Yao Lu,YuZhe Bai,FengKun Ji,Li Zhang,RunGong Yang,Xiaobing Fu
Background Chronic refractory wounds are a common complication in diabetic patients. Adipose-derived mesenchymal stem cells (ASCs) have been shown to play an essential role in diabetic wound repair. Aims To determine whether a composite of ASCs and sodium alginate/gelatin (Gel-Al) hydrogel can promote diabetic wound healing. Methods Full-thickness cutaneous wounds were created in streptozotocin-induced diabetic rats prior to treatment with Gel-Al hydrogels loaded with ASCs. Hydrogel biocompatibility and wound healing were analyzed. Hematoxylin and eosin staining, Masson staining, immunofluorescence, enzyme-linked immunosorbent assays (ELISA), and quantitative real-time PCR were performed for the assessment of cellular responses. Results Compared to the control group or Gel-Al alone group, the combination of Gel-Al and ASCs promoted wound closure, facilitated granulation tissue regeneration and collagen deposition, and upregulated the expression of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and endothelial cell marker CD31. Moreover, the combination of Gel-Al and ASCs decreased interleukin-6 (IL-6) and interleukin-1β (IL-1β) expression, increased transforming growth factor beta1 (TGFβ1), interleukin-10 (IL-10), interleukin-4 (IL-4) and interleukin-13 (IL-13) expression, and increased M2 macrophage polarization. Conclusions Gel-Al hydrogels loaded with ASCs accelerate diabetic wound healing. The Gel-Al hydrogel-based ASC system therefore represents an innovative therapeutic strategy for diabetic wound repair.
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Biomedical Physics & Engineering Express
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2023
·Vol. 9
·期 3
·035027
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IF 1.4
Danni Wang,Xingming Wang,Ximing Pu,Guangfu Yin,Zhenrong Zhu,Xiaoran An,Wen Zhang
The high wastage rate and low survival rate of seed cells in conventional bone tissue engineering (BTE) are always a challenge for tissue regeneration. Constructing scaffolds that could continuously recruit endogenous stem cells is considered a novel way to promote tissue repair. In this study, a GelMA fiber hydrogel membrane loaded interleukin 8 (IL8) (IL8-GelMA), was prepared via electrostatic spinning technology. Compared with Gelatin fiber, GelMA fiber possessed a smooth morphology with nanoscale diameter and better physical properties including hydrophilicity, elastic modulus, swelling rate and degradation rate. In addition, IL8-GelMA fiber membranes could lead an osteogenic differentiation of BMSCs. Moreover, the results of chemotaxis experiment demonstrated that both IL8 and IL8-GelMA fiber membranes promote the migration of BMSCs in vitro. These results suggested that IL8-GelMA fiber membranes can be used for cell-free scaffold of bone repair, which can not only recruit endogenous BMSCs, but also promote osteogenic differentiation of BMSCs.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Teng Wang,Yang Yu,Bingjie Wang,Tianze Jiang,Xin Meng,Xia Zhao
Recurrence and metastasis have been recognized as a great challenge in cancer treatment. Cancer stem cells (CSCs), as a small subset of cancer cells, are closely associated with tumor metastasis and recurrence due to their resistance and multi-differentiation characteristics. Herein, we developed a local injectable hyaluronic acid (HA) composite hydrogel (HAAG) that targets CSCs, which can continuously release all-trans retinoic acid (ATRA) and gold nanoparticles (AuNPs) at tumor sites. The composite hydrogel was endowed with the ability to target CSCs through the specific binding of HA to CD44. ATRA was loaded into HA micelles to induce CSCs to differentiate into normal cancer cells, while AuNPs was incorporated into the hydrogel for photothermal therapy (PTT). HAAG exhibited good injectability, photothermal properties and CSCs targeting ability. HAAG not only significantly inhibited the growth of 4T1 mouse breast cancer cells and 4T1-CSCs in vitro , but also effectively inhibited tumor recurrence and metastasis in a 4T1-CSC mouse model in vivo . Our study provides a novel strategy of local differentiation combined with PTT for inhibiting the recurrence and metastasis of breast cancer.
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Small
·
2023
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IF 13.3
Yuan Li,Kuo Zhang,Xuezheng Ai,Qingshi Zhang,Lu Jiang,Jiang Long,Huange Xu,Chencheng Feng,Yaqing Zhang,Guoke Tang,Fanli Chong,Lei Wang,Bo Huang
Maintaining quiescence of stem cells is a potential way to decrease cell nutrition demand for restoring the organization. Herein, a biomimetic peptide to maintain quiescence of stem cells through C-X-C motif chemokine ligand 8 (CXCL8)-C-X-C motif chemokine receptor 1 (CXCR1) pathway against intervertebral disc degeneration (IVDD) is developed. First, it is confirmed that quiescence can be induced via inhibiting phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in nucleus pulposus stem cells (NPSCs). Meanwhile, it is well known that CXCR1, a chemokine receptor, can be targeted by CXCL8, resulting in cell proliferation via activating PI3K/Akt/mTOR pathway. Second, a biomimetic peptide (OAFF) that can bind to CXCR1 and form fibrous networks on NPSCs, mimicking extracellular matrix formation is developed. The multivalent effect and long-term binding to CXCR1 on NPSCs of OAFF fibers offer forcefully competitive inhibition with natural CXCL8, which induces NPSCs quiescence and ultimately overcomes obstacle in intradiscal injection therapy. In rat caudal disc puncture model, OAFF nanofibers still maintain at 5 weeks after operation and inhibit degeneration process of intervertebral disc in terms of histopathology and imageology. In situ fibrillogenesis of biomimetic peptide on NPSCs provides promising stem cells for intradiscal injection therapy against IVDD.
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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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Advanced Healthcare Materials
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2023
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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
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2023
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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
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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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