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Enzyme-responsive vitamin D-based micelles for paclitaxel-controlled delivery and synergistic pancreatic cancer therapy
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-04 DOI: 10.1016/j.mtbio.2025.101555
Diana Peixoto , João M. Ravasco , Barbara Blanco-Fernandez , Francisco Veiga , Angel Concheiro , João Conde , Ana Cláudia Paiva-Santos , Carmen Alvarez-Lorenzo
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most feared diseases worldwide owing to its poor prognosis, negligible therapeutic advances, and high mortality. Herein, multifunctional enzyme-responsive micelles for the controlled delivery of paclitaxel (PTX) were prepared to circumvent its current clinical challenges. Accordingly, two enzyme-responsive structural units composed of Vitamin D3 (VD3) conjugated with polyethylene glycol of different molecular weights (600 Da and 2000 Da) were synthesized and characterized using different analytical methods. By applying the solvent evaporation method, these bioactive structural units self-assembled into sub-100 nm VD3 micelles with minimal batch-to-batch variation, monomodal particle size distribution, and high encapsulation efficiency. The enzyme-triggered disassembly of PTX-loaded VD3 micelles was demonstrated by release studies in the presence of a high esterase content typically featured by PDAC cells. PTX-loaded VD3 micelles also exhibited prominent cell internalization and induced a considerable cytotoxic synergistic effect against human PDAC cells (BxPC-3 cells) in 2D and 3D cell culture models compared with free PTX. The PTX-loaded VD3 micelles were hemocompatible and stable after long-term storage in the presence of biorelevant media, and showed higher efficiency to inhibit the tumor growth compared to the approved clinical nanoformulation (Abraxane®) in an in ovo tumor model. The findings reported here indicate that VD3S-PEG micelles may have a promising role in PDAC therapy, since VD3 could act not only as a hydrophobic core of the micelles but also as a therapeutic agent that provides synergetic therapeutic effects with the encapsulated PTX.
{"title":"Enzyme-responsive vitamin D-based micelles for paclitaxel-controlled delivery and synergistic pancreatic cancer therapy","authors":"Diana Peixoto ,&nbsp;João M. Ravasco ,&nbsp;Barbara Blanco-Fernandez ,&nbsp;Francisco Veiga ,&nbsp;Angel Concheiro ,&nbsp;João Conde ,&nbsp;Ana Cláudia Paiva-Santos ,&nbsp;Carmen Alvarez-Lorenzo","doi":"10.1016/j.mtbio.2025.101555","DOIUrl":"10.1016/j.mtbio.2025.101555","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) remains one of the most feared diseases worldwide owing to its poor prognosis, negligible therapeutic advances, and high mortality. Herein, multifunctional enzyme-responsive micelles for the controlled delivery of paclitaxel (PTX) were prepared to circumvent its current clinical challenges. Accordingly, two enzyme-responsive structural units composed of Vitamin D<sub>3</sub> (VD<sub>3</sub>) conjugated with polyethylene glycol of different molecular weights (600 Da and 2000 Da) were synthesized and characterized using different analytical methods. By applying the solvent evaporation method, these bioactive structural units self-assembled into sub-100 nm VD<sub>3</sub> micelles with minimal batch-to-batch variation, monomodal particle size distribution, and high encapsulation efficiency. The enzyme-triggered disassembly of PTX-loaded VD<sub>3</sub> micelles was demonstrated by release studies in the presence of a high esterase content typically featured by PDAC cells. PTX-loaded VD<sub>3</sub> micelles also exhibited prominent cell internalization and induced a considerable cytotoxic synergistic effect against human PDAC cells (BxPC-3 cells) in 2D and 3D cell culture models compared with free PTX. The PTX-loaded VD<sub>3</sub> micelles were hemocompatible and stable after long-term storage in the presence of biorelevant media, and showed higher efficiency to inhibit the tumor growth compared to the approved clinical nanoformulation (Abraxane®) in an <em>in ovo</em> tumor model. The findings reported here indicate that VD<sub>3</sub>S-PEG micelles may have a promising role in PDAC therapy, since VD<sub>3</sub> could act not only as a hydrophobic core of the micelles but also as a therapeutic agent that provides synergetic therapeutic effects with the encapsulated PTX.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101555"},"PeriodicalIF":8.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Improving ferroptosis-mediated immunotherapy for colorectal cancer through lysosome-targeted photodynamic therapy
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-04 DOI: 10.1016/j.mtbio.2025.101552
Zhian Chen , Yutong Wang , Zhenhao Li , Meijuan Chen , Yingshi Li , Chuyue Lu , Zhenyu Lin , Hua Zheng , Lujia Chen , Qianbing Zhang
Lysosomes is emerging as a promising therapeutic target for improving immunotherapy, which dysfunction would trigger lysosomal membrane permeabilization increase and subsequent leakage of reduced iron, which contributed to ferroptosis through cell-intrinsic Fenton chemistry. However, the integrity of lysosomal membranes is not susceptible to disrupt, owing to the presence of several Endo-lysosomal damage-response mechanisms. Herein, we developed a lysosome-targeted photosensitizer (TLA), which possessed robust light stability, good bio-compatibility, and high photodynamic therapy (PDT) effect. Upon internalized by cancer cells, TLA was specifically accumulated in lysosome, and which would destroy the integrity of lysosomal membranes and inhibit protective autophagy upon exposure to light irradiation. Subsequently, the cancer cells were suffered from ferroptosis through triggering cell-intrinsic Fenton chemistry and mitochondrial dysfunction, which would release damage-associated molecular pattern molecules (DAMPs) to induce immunogenic cell death and remodel immunosuppressive tumor microenvironment. Notably, combined with PD-L1 antibody and TLA could greatly potentiate the immune response and exhibit highest anti-tumor effects. In summary, this novel lysosome-targeted photosensitizer could serve as a promising strategy for the treatment of colorectal cancer.
{"title":"Improving ferroptosis-mediated immunotherapy for colorectal cancer through lysosome-targeted photodynamic therapy","authors":"Zhian Chen ,&nbsp;Yutong Wang ,&nbsp;Zhenhao Li ,&nbsp;Meijuan Chen ,&nbsp;Yingshi Li ,&nbsp;Chuyue Lu ,&nbsp;Zhenyu Lin ,&nbsp;Hua Zheng ,&nbsp;Lujia Chen ,&nbsp;Qianbing Zhang","doi":"10.1016/j.mtbio.2025.101552","DOIUrl":"10.1016/j.mtbio.2025.101552","url":null,"abstract":"<div><div>Lysosomes is emerging as a promising therapeutic target for improving immunotherapy, which dysfunction would trigger lysosomal membrane permeabilization increase and subsequent leakage of reduced iron, which contributed to ferroptosis through cell-intrinsic Fenton chemistry. However, the integrity of lysosomal membranes is not susceptible to disrupt, owing to the presence of several Endo-lysosomal damage-response mechanisms. Herein, we developed a lysosome-targeted photosensitizer (TLA), which possessed robust light stability, good bio-compatibility, and high photodynamic therapy (PDT) effect. Upon internalized by cancer cells, TLA was specifically accumulated in lysosome, and which would destroy the integrity of lysosomal membranes and inhibit protective autophagy upon exposure to light irradiation. Subsequently, the cancer cells were suffered from ferroptosis through triggering cell-intrinsic Fenton chemistry and mitochondrial dysfunction, which would release damage-associated molecular pattern molecules (DAMPs) to induce immunogenic cell death and remodel immunosuppressive tumor microenvironment. Notably, combined with PD-L1 antibody and TLA could greatly potentiate the immune response and exhibit highest anti-tumor effects. In summary, this novel lysosome-targeted photosensitizer could serve as a promising strategy for the treatment of colorectal cancer.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101552"},"PeriodicalIF":8.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lymph node-targeted delivery of Lonicera japonica thunb. polysaccharides for enhancing antitumor immunotherapy
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-04 DOI: 10.1016/j.mtbio.2025.101559
Jiatong Zhang , Jintong Liu , Hong Zhang , Biao Liu , Lujie Li , Yifan Li , Jingrou Pei , Qiao Lin , Qi Chen , Jiahao Lin
Dendritic cells (DCs) are crucial for the initiation and regulation of innate and adaptive immunity. Their maturity and infiltration in the tumor largely determine the efficiency of antigen presentation, the CTL responses, and the prognosis of tumors. However, the application of common immunoregulatory plant polysaccharides to DCs in vivo still represents major challenges due to the off-target effect and short biological lifespan. Lonicera japonica Thunb. polysaccharides (LJP) were found to exert benign immunoregulatory ability, but the effectiveness of utilizing LJP alone is unsatisfactory. As a result, we innovatively encapsulated LJP in into the exosomes derived from mouse bone mesenchymal stem cells (BMSCs) to form a DC-activated inducer (LJP-exosome). LJP-exosomes possessed a profound ability to target lymph nodes and the co-stimulatory capability of DCs compared with the application of LJP alone. Adequate results have shown that DCs primed by LJP-exosomes enhanced the tumor-reactive CD8+ T cell responses, leading to prophylactic tumor inhibition in an immunologically ignorant tumor model. The study proposed offers a promising strategy for enhancing the immune activation efficacy of extracted polysaccharides of traditional Chinese medicine by building the patients’ immunity, thus consolidating the overall prognosis.
{"title":"Lymph node-targeted delivery of Lonicera japonica thunb. polysaccharides for enhancing antitumor immunotherapy","authors":"Jiatong Zhang ,&nbsp;Jintong Liu ,&nbsp;Hong Zhang ,&nbsp;Biao Liu ,&nbsp;Lujie Li ,&nbsp;Yifan Li ,&nbsp;Jingrou Pei ,&nbsp;Qiao Lin ,&nbsp;Qi Chen ,&nbsp;Jiahao Lin","doi":"10.1016/j.mtbio.2025.101559","DOIUrl":"10.1016/j.mtbio.2025.101559","url":null,"abstract":"<div><div>Dendritic cells (DCs) are crucial for the initiation and regulation of innate and adaptive immunity. Their maturity and infiltration in the tumor largely determine the efficiency of antigen presentation, the CTL responses, and the prognosis of tumors. However, the application of common immunoregulatory plant polysaccharides to DCs <em>in vivo</em> still represents major challenges due to the off-target effect and short biological lifespan. <em>Lonicera japonica</em> Thunb. polysaccharides (LJP) were found to exert benign immunoregulatory ability, but the effectiveness of utilizing LJP alone is unsatisfactory. As a result, we innovatively encapsulated LJP in into the exosomes derived from mouse bone mesenchymal stem cells (BMSCs) to form a DC-activated inducer (LJP-exosome). LJP-exosomes possessed a profound ability to target lymph nodes and the co-stimulatory capability of DCs compared with the application of LJP alone. Adequate results have shown that DCs primed by LJP-exosomes enhanced the tumor-reactive CD8<sup>+</sup> T cell responses, leading to prophylactic tumor inhibition in an immunologically ignorant tumor model. The study proposed offers a promising strategy for enhancing the immune activation efficacy of extracted polysaccharides of traditional Chinese medicine by building the patients’ immunity, thus consolidating the overall prognosis.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101559"},"PeriodicalIF":8.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sustained slow-release TGF-β3 in a three-dimensional-printed titanium microporous scaffold composite system promotes ligament-to-bone healing
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-04 DOI: 10.1016/j.mtbio.2025.101549
Liwei Zhu, Yuzhe Liu, Yifu Sun, Zhenjia Che, Youbin Li, Tengyue Liu, Xudong Li, Chengzhe Yang, Lanfeng Huang
The treatment of tendon/ligament-to-bone injury is a long-standing research challenge in orthopedics and bone tissue engineering. Orderly healing of the fibrocartilage layer and mineralized bone layer is crucial for treating tendon-bone interface injuries. We designed a three-dimensional printed porous titanium scaffold composite system with thermosensitive collagen hydrogel loaded with transforming growth factor β3 (TGF-β3), formulated for the sustained slow release of TGF-β3 at a constant rate. In vitro, the composite system exhibited good biocompatibility and was beneficial for the adhesion and proliferation of bone marrow mesenchymal stem cells (BMSCs), which showed high growth activity. Moreover, the composite system promoted the differentiation of BMSCs via osteogenesis and chondrogenesis. In vivo, the composite system provided active substances at the injured site, promoting the repair of the fibrocartilage layer and of the mineralized bone layer at the interface between the ligament and bone. Micro-CT results demonstrated that the complex promotes the osseointegration of titanium scaffolds in bone defects. Hard tissue sections showed that the new bone, ligament, and the titanium alloy scaffold system formed a closely integrated whole; the composite system provided suitable attachment points for ligament growth. Additionally, the biomechanical strength of the tendon interface improved to some extent. Our results indicate that the composite system has potential as a bioactive implant interface for repairing ligament and bone injuries.
{"title":"Sustained slow-release TGF-β3 in a three-dimensional-printed titanium microporous scaffold composite system promotes ligament-to-bone healing","authors":"Liwei Zhu,&nbsp;Yuzhe Liu,&nbsp;Yifu Sun,&nbsp;Zhenjia Che,&nbsp;Youbin Li,&nbsp;Tengyue Liu,&nbsp;Xudong Li,&nbsp;Chengzhe Yang,&nbsp;Lanfeng Huang","doi":"10.1016/j.mtbio.2025.101549","DOIUrl":"10.1016/j.mtbio.2025.101549","url":null,"abstract":"<div><div>The treatment of tendon/ligament-to-bone injury is a long-standing research challenge in orthopedics and bone tissue engineering. Orderly healing of the fibrocartilage layer and mineralized bone layer is crucial for treating tendon-bone interface injuries. We designed a three-dimensional printed porous titanium scaffold composite system with thermosensitive collagen hydrogel loaded with transforming growth factor β3 (TGF-β3), formulated for the sustained slow release of TGF-β3 at a constant rate. <em>In vitro</em>, the composite system exhibited good biocompatibility and was beneficial for the adhesion and proliferation of bone marrow mesenchymal stem cells (BMSCs), which showed high growth activity. Moreover, the composite system promoted the differentiation of BMSCs via osteogenesis and chondrogenesis. <em>In vivo</em>, the composite system provided active substances at the injured site, promoting the repair of the fibrocartilage layer and of the mineralized bone layer at the interface between the ligament and bone. Micro-CT results demonstrated that the complex promotes the osseointegration of titanium scaffolds in bone defects. Hard tissue sections showed that the new bone, ligament, and the titanium alloy scaffold system formed a closely integrated whole; the composite system provided suitable attachment points for ligament growth. Additionally, the biomechanical strength of the tendon interface improved to some extent. Our results indicate that the composite system has potential as a bioactive implant interface for repairing ligament and bone injuries.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101549"},"PeriodicalIF":8.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integrated microfluidics-based construction of anti-BTN2A2 gel droplet cell preparations for non-invasive tumor-infiltrating lymphocyte therapy
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-04 DOI: 10.1016/j.mtbio.2025.101545
Yishen Tian , Jingxuan Li , Na Yang , Yang Zhao , Jiancao Zuo , Hang Xiong , Yiwen Pan , Li Xiao , Min Su , Feng Han , Zhixu He , Rong Hu
Tumor infiltrating lymphocyte therapy (TIL therapy) is one of the effective treatments for solid tumors. However, certain periods or sites of solid tumors are not amenable to surgical resection. Meanwhile, the abundant and dense extracellular matrix (ECM) and regulatory cells (e.g., regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSC)) in solid tumors when infused back into the treatment will prevent T cell infiltration and proliferation, thus inhibiting the efficacy of this approach. In this study, a novel cell preparation was successfully developed by integrating microfluidic chip design with carbodiimide chemical modification. This preparation was surface modified with BTN2A2 antibodies and internally contained T cells isolated from the blood of tumor hosts, along with simulated collagen peptide CMP. Specifically, the cell preparation exerted its anti-tumor effects through multiple mechanisms: Firstly, the surface BTN2A2 antibodies effectively inhibited the proliferation of Tregs and MDSCs within the tumor microenvironment; Secondly, leveraging the T cell antigen receptors (TCRs) present in the blood T cells, which were similar to those of tumor-infiltrating lymphocytes, significantly enhanced their targeting and cytotoxic capabilities; Furthermore, the CMP component within the droplets effectively promoted the infiltration of T cells into tumor tissues. In the complex immunosuppressive microenvironment, the synergistic action of these components markedly enhanced the clearance efficacy of the immune system. Experimental results demonstrated that this cellular preparation exhibited promising therapeutic effects in both melanoma and pancreatic cancer models. This research provided a novel platform for the synergistic cooperation of various methods in tumor immunotherapy, holding broad application prospects.
{"title":"Integrated microfluidics-based construction of anti-BTN2A2 gel droplet cell preparations for non-invasive tumor-infiltrating lymphocyte therapy","authors":"Yishen Tian ,&nbsp;Jingxuan Li ,&nbsp;Na Yang ,&nbsp;Yang Zhao ,&nbsp;Jiancao Zuo ,&nbsp;Hang Xiong ,&nbsp;Yiwen Pan ,&nbsp;Li Xiao ,&nbsp;Min Su ,&nbsp;Feng Han ,&nbsp;Zhixu He ,&nbsp;Rong Hu","doi":"10.1016/j.mtbio.2025.101545","DOIUrl":"10.1016/j.mtbio.2025.101545","url":null,"abstract":"<div><div>Tumor infiltrating lymphocyte therapy (TIL therapy) is one of the effective treatments for solid tumors. However, certain periods or sites of solid tumors are not amenable to surgical resection. Meanwhile, the abundant and dense extracellular matrix (ECM) and regulatory cells (e.g., regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSC)) in solid tumors when infused back into the treatment will prevent T cell infiltration and proliferation, thus inhibiting the efficacy of this approach. In this study, a novel cell preparation was successfully developed by integrating microfluidic chip design with carbodiimide chemical modification. This preparation was surface modified with BTN2A2 antibodies and internally contained T cells isolated from the blood of tumor hosts, along with simulated collagen peptide CMP. Specifically, the cell preparation exerted its anti-tumor effects through multiple mechanisms: Firstly, the surface BTN2A2 antibodies effectively inhibited the proliferation of Tregs and MDSCs within the tumor microenvironment; Secondly, leveraging the T cell antigen receptors (TCRs) present in the blood T cells, which were similar to those of tumor-infiltrating lymphocytes, significantly enhanced their targeting and cytotoxic capabilities; Furthermore, the CMP component within the droplets effectively promoted the infiltration of T cells into tumor tissues. In the complex immunosuppressive microenvironment, the synergistic action of these components markedly enhanced the clearance efficacy of the immune system. Experimental results demonstrated that this cellular preparation exhibited promising therapeutic effects in both melanoma and pancreatic cancer models. This research provided a novel platform for the synergistic cooperation of various methods in tumor immunotherapy, holding broad application prospects.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101545"},"PeriodicalIF":8.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143378943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nanozyme based ultra-stretchable, low-hysteresis, and dual-mode antibacterial composite hydrogels for wound healing
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-03 DOI: 10.1016/j.mtbio.2025.101547
Yanyan Li , Weiqi Kang , Jian Zhang , Ping Shi , Jianshu Li , Yongping Lu
Wound care always presents challenges as they are susceptible to bacterial infections and have mechanical compatibility issues with wound dressings, leading to a delayed recovery of the structure and functional integrity of skin tissue. Herein, an iron-based metal-organic framework loaded with gold (Fe-MIL-88NH2-Au) nanozyme based composite hydrogel (HMAux) with excellent mechanical compatibility and dual-mode antibacterial properties was designed for wound care. To obtain HMAux, Fe-MIL-88NH2-Au nanozyme with photothermal properties and peroxidase-like and oxidase-like activities was prepared. Then it was introduced into the hydrogel system with a sea-island structure which was prepared via the copolymerization of acrylamide and acryloyl Pluronic F127 (PF127-DA) in the aqueous solution. Using dynamic micelles as the energy dissipation mechanism, double bonds and intermolecular interactions as two crosslinking methods in HMAux make it possess good stretchability (3244 %–4524 %), toughness (593.8 kJ/m3 to 421.5 kJ/m3), and low hysteresis (0.13–0.15). Furthermore, the synergistic photothermal and chemodynamic effects provide good antibacterial performance under mild conditions, with killing rates of approximately 95.02 % and 97.28 % for S. aureus and E. coli, respectively. In vivo experiments have proved that HMAux can effectively adapt to the contour of the wound and treat wound infections.
{"title":"Nanozyme based ultra-stretchable, low-hysteresis, and dual-mode antibacterial composite hydrogels for wound healing","authors":"Yanyan Li ,&nbsp;Weiqi Kang ,&nbsp;Jian Zhang ,&nbsp;Ping Shi ,&nbsp;Jianshu Li ,&nbsp;Yongping Lu","doi":"10.1016/j.mtbio.2025.101547","DOIUrl":"10.1016/j.mtbio.2025.101547","url":null,"abstract":"<div><div>Wound care always presents challenges as they are susceptible to bacterial infections and have mechanical compatibility issues with wound dressings, leading to a delayed recovery of the structure and functional integrity of skin tissue. Herein, an iron-based metal-organic framework loaded with gold (Fe-MIL-88NH<sub>2</sub>-Au) nanozyme based composite hydrogel (HMAux) with excellent mechanical compatibility and dual-mode antibacterial properties was designed for wound care. To obtain HMAux, Fe-MIL-88NH<sub>2</sub>-Au nanozyme with photothermal properties and peroxidase-like and oxidase-like activities was prepared. Then it was introduced into the hydrogel system with a sea-island structure which was prepared <em>via</em> the copolymerization of acrylamide and acryloyl Pluronic F127 (PF127-DA) in the aqueous solution. Using dynamic micelles as the energy dissipation mechanism, double bonds and intermolecular interactions as two crosslinking methods in HMAux make it possess good stretchability (3244 %–4524 %), toughness (593.8 kJ/m<sup>3</sup> to 421.5 kJ/m<sup>3</sup>), and low hysteresis (0.13–0.15). Furthermore, the synergistic photothermal and chemodynamic effects provide good antibacterial performance under mild conditions, with killing rates of approximately 95.02 % and 97.28 % for <em>S. aureus</em> and <em>E. coli</em>, respectively. <em>In vivo</em> experiments have proved that HMAux can effectively adapt to the contour of the wound and treat wound infections.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101547"},"PeriodicalIF":8.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Designing hydrogel for application in spinal surgery
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-03 DOI: 10.1016/j.mtbio.2025.101536
Rongpeng Dong, Shuang Zheng, Xueliang Cheng
Spinal diseases and injuries are prevalent in clinical settings and impose a substantial burden on healthcare systems. Current treatments for spinal diseases are predominantly limited to surgical interventions, drug injections, and conservative treatments. Generally, these treatment modalities have limited or no long-term benefits. Hydrogel-based treatments have emerged as potentially powerful paradigms for improving therapeutic outcomes and the quality of life of patients. Hydrogels can be injected into target sites, including the epidural, intraspinal, and nucleus pulposus spaces, in a minimally invasive manner and fill defects to provide mechanical support. Hydrogels can be designed for the localized and controlled delivery of pharmacological agents to enhance therapeutic effects and reduce adverse reactions. Hydrogels can act as structural supports for transplanted cells to improve cell survival, proliferation, and differentiation, as well as integration into adjacent host tissues. In this review, we summarize recent advances in the design of hydrogels for the treatment of spinal diseases and injuries commonly found in clinical settings, including intervertebral disc degeneration, spinal cord injury, and dural membrane injury. We introduce the design considerations for different hydrogel systems, including precursor polymers and crosslinking mechanisms. Herein, we discuss the therapeutic outcomes of these hydrogels in terms of providing mechanical support, delivering cells/bioactive agents, regulating local inflammation, and promoting tissue regeneration and functional recovery.
{"title":"Designing hydrogel for application in spinal surgery","authors":"Rongpeng Dong,&nbsp;Shuang Zheng,&nbsp;Xueliang Cheng","doi":"10.1016/j.mtbio.2025.101536","DOIUrl":"10.1016/j.mtbio.2025.101536","url":null,"abstract":"<div><div>Spinal diseases and injuries are prevalent in clinical settings and impose a substantial burden on healthcare systems. Current treatments for spinal diseases are predominantly limited to surgical interventions, drug injections, and conservative treatments. Generally, these treatment modalities have limited or no long-term benefits. Hydrogel-based treatments have emerged as potentially powerful paradigms for improving therapeutic outcomes and the quality of life of patients. Hydrogels can be injected into target sites, including the epidural, intraspinal, and nucleus pulposus spaces, in a minimally invasive manner and fill defects to provide mechanical support. Hydrogels can be designed for the localized and controlled delivery of pharmacological agents to enhance therapeutic effects and reduce adverse reactions. Hydrogels can act as structural supports for transplanted cells to improve cell survival, proliferation, and differentiation, as well as integration into adjacent host tissues. In this review, we summarize recent advances in the design of hydrogels for the treatment of spinal diseases and injuries commonly found in clinical settings, including intervertebral disc degeneration, spinal cord injury, and dural membrane injury. We introduce the design considerations for different hydrogel systems, including precursor polymers and crosslinking mechanisms. Herein, we discuss the therapeutic outcomes of these hydrogels in terms of providing mechanical support, delivering cells/bioactive agents, regulating local inflammation, and promoting tissue regeneration and functional recovery.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101536"},"PeriodicalIF":8.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143101119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
NIR-triggered programmable nanomotor with H2S and NO generation for cascading oncotherapy by three-pronged reinforcing ICD
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-03 DOI: 10.1016/j.mtbio.2025.101540
Jinlong Zhang , Quan Jing , Longlong Yuan , Xianhui Zhou , Duolong Di , Jinyao Li , Dong Pei , Zhongxiong Fan , Jun Hai
Gas therapy (GT) and/or phototherapy have been recently employed as immunogenic cell death (ICD) agents for activating immunotherapy, whereas the effective activation of sufficient immune responses remains an enormous challenge in such single therapeutic modality. In this study, a near-infrared (NIR)-triggered programmable nanomotor with hydrogen sulfide (H2S) and nitric oxide (NO) generation is well designed to achieve oncotherapy by cascading mild photothermal, gas, and reactive oxygen species (ROS)-reinforced immunogenic cell death. In brief, a gas signal molecule donor NOSH with H2S and NO capable of on-demand H2S and NO release was synthesized and then loaded into hollow mesoporous copper sulfide nanoparticles (termed as HCuSNPs) with an inherent NIR absorption and surface modification activity to obtain the programmable nanomotor (termed as NOSH@PEG-HCuSNPs). In particular, NOSH@PEG-HCuSNPs can effectively achieve the simultaneous spatiotemporal co-delivery of NOSH and HCuSNPs, thereby exerting the synergistic effects of GT and mild photothermal therapy (mPTT). It is worth noting that the anti-tumor response of mPTT is effectively enhanced by GT by disrupting the mitochondrial respiratory chain, inhibiting ATP production, and promoting tumor cell apoptosis. One by one, a large number of peroxynitrite anion (ONOO) radicals are generated by the interactions of ROS from mPTT and NO from NOSH. Meanwhile, the unique protective mechanism of H2S is utilized to induce tumor thermal ablation by reducing the overexpression of heat shock protein 90 (HSP 90) and minimize the unnecessary damage toward normal tissues. Finally, ICD is markedly augmented by the cascading effects of mPTT, ONOO⁻radicals, and H2S. Concurrently, the immunosuppressive tumor microenvironment is reprogrammed, effectively inhibiting distant tumor tissues and preventing metastasis and tumor recurrence. Taken together, this study provides a new perspective for innovation in the field of oncotherapy.
{"title":"NIR-triggered programmable nanomotor with H2S and NO generation for cascading oncotherapy by three-pronged reinforcing ICD","authors":"Jinlong Zhang ,&nbsp;Quan Jing ,&nbsp;Longlong Yuan ,&nbsp;Xianhui Zhou ,&nbsp;Duolong Di ,&nbsp;Jinyao Li ,&nbsp;Dong Pei ,&nbsp;Zhongxiong Fan ,&nbsp;Jun Hai","doi":"10.1016/j.mtbio.2025.101540","DOIUrl":"10.1016/j.mtbio.2025.101540","url":null,"abstract":"<div><div>Gas therapy (GT) and/or phototherapy have been recently employed as immunogenic cell death (ICD) agents for activating immunotherapy, whereas the effective activation of sufficient immune responses remains an enormous challenge in such single therapeutic modality. In this study, a near-infrared (NIR)-triggered programmable nanomotor with hydrogen sulfide (H<sub>2</sub>S) and nitric oxide (NO) generation is well designed to achieve oncotherapy by cascading mild photothermal, gas, and reactive oxygen species (ROS)-reinforced immunogenic cell death. In brief, a gas signal molecule donor NOSH with H<sub>2</sub>S and NO capable of on-demand H<sub>2</sub>S and NO release was synthesized and then loaded into hollow mesoporous copper sulfide nanoparticles (termed as HCuSNPs) with an inherent NIR absorption and surface modification activity to obtain the programmable nanomotor (termed as NOSH@PEG-HCuSNPs). In particular, NOSH@PEG-HCuSNPs can effectively achieve the simultaneous spatiotemporal co-delivery of NOSH and HCuSNPs, thereby exerting the synergistic effects of GT and mild photothermal therapy (mPTT). It is worth noting that the anti-tumor response of mPTT is effectively enhanced by GT by disrupting the mitochondrial respiratory chain, inhibiting ATP production, and promoting tumor cell apoptosis. One by one, a large number of peroxynitrite anion (ONOO<sup>−</sup>) radicals are generated by the interactions of ROS from mPTT and NO from NOSH. Meanwhile, the unique protective mechanism of H<sub>2</sub>S is utilized to induce tumor thermal ablation by reducing the overexpression of heat shock protein 90 (HSP 90) and minimize the unnecessary damage toward normal tissues. Finally, ICD is markedly augmented by the cascading effects of mPTT, ONOO⁻radicals, and H<sub>2</sub>S. Concurrently, the immunosuppressive tumor microenvironment is reprogrammed, effectively inhibiting distant tumor tissues and preventing metastasis and tumor recurrence. Taken together, this study provides a new perspective for innovation in the field of oncotherapy.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101540"},"PeriodicalIF":8.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143271774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The anti-depression effect and mechanism of harmonious rosemary essential oil and its application in microcapsules
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-03 DOI: 10.1016/j.mtbio.2025.101546
Yunwei Niu, Liyang Xu, Mengdong Qiao, Yamei Wang
Depression imposes a heavy burden on patients and society, and current antidepressants often cause side effects such as dryness in the mouth and constipation. The explorations about aromatic plant essential oils provide a new method for the treatment of depression, but the mechanisms of antidepressant effect of these oils are not deeply enough. Here, the rosemary essential oil analyzed by GC-O and GC-MS techniques, whose main aromatic compounds are determined as 1,8-cineole (OAV = 1869.27, AI = 9.4), linalool (OAV = 1668.90, AI = 5.4), and ethyl decanoate (OAV = 1169.09, AI = 6.9). The network pharmacology was employed to investigate the possible pathway of action for antidepressant effects of the rosemary essential oil, and Gface software that can capture facial expressions was used to harmony the aroma to make the oil more pleasant. Then, the harmonious essential oil was proved to have antidepressant effects. For addressing issues of strong volatility and oxidation susceptibility of essential oil, dendrimer-like γ-cyclodextrin was prepared and encapsulate the essential oil. The obtained microcapsule prolonged fragrance duration and presented good stability, which are applied in aromatherapy and daily care products. This study lays a theoretical and methodological foundation for essential oil efficacy research and provides new strategies for designing and producing functional products related to essential oils.
{"title":"The anti-depression effect and mechanism of harmonious rosemary essential oil and its application in microcapsules","authors":"Yunwei Niu,&nbsp;Liyang Xu,&nbsp;Mengdong Qiao,&nbsp;Yamei Wang","doi":"10.1016/j.mtbio.2025.101546","DOIUrl":"10.1016/j.mtbio.2025.101546","url":null,"abstract":"<div><div>Depression imposes a heavy burden on patients and society, and current antidepressants often cause side effects such as dryness in the mouth and constipation. The explorations about aromatic plant essential oils provide a new method for the treatment of depression, but the mechanisms of antidepressant effect of these oils are not deeply enough. Here, the rosemary essential oil analyzed by GC-O and GC-MS techniques, whose main aromatic compounds are determined as 1,8-cineole (OAV = 1869.27, AI = 9.4), linalool (OAV = 1668.90, AI = 5.4), and ethyl decanoate (OAV = 1169.09, AI = 6.9). The network pharmacology was employed to investigate the possible pathway of action for antidepressant effects of the rosemary essential oil, and Gface software that can capture facial expressions was used to harmony the aroma to make the oil more pleasant. Then, the harmonious essential oil was proved to have antidepressant effects. For addressing issues of strong volatility and oxidation susceptibility of essential oil, dendrimer-like γ-cyclodextrin was prepared and encapsulate the essential oil. The obtained microcapsule prolonged fragrance duration and presented good stability, which are applied in aromatherapy and daily care products. This study lays a theoretical and methodological foundation for essential oil efficacy research and provides new strategies for designing and producing functional products related to essential oils.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101546"},"PeriodicalIF":8.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143100610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
High paracrine activity of hADSCs cartilage microtissues inhibits extracellular matrix degradation and promotes cartilage regeneration 高旁分泌活性的hascs软骨微组织抑制细胞外基质降解,促进软骨再生
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-01 DOI: 10.1016/j.mtbio.2024.101372
Wei Liu , Hongyu Jiang , Jiajie Chen , Yue Tian , Ying He , Ying Jiao , Yanjun Guan , Zhibo Jia , Yanbin Wu , Cheng Huang , Yiben Ouyang , Wenjing Xu , Jianhong Qi , Jiang Peng , Aiyuan Wang
Due to its unique structure, articular cartilage has limited self-repair capacity. Microtissues are tiny tissue clusters that can mimic the function of target organs or tissues. Using cells alone for microtissue construction often results in the formation of necrotic cores. However, the extracellular matrix (ECM) of native cartilage can provide structural support and is an ideal source of microcarriers. Autologous adipose-derived mesenchymal stem cells (ADSCs) and bone marrow mesenchymal stem cells (BMSCs) are widely used in cartilage tissue engineering. In this study, we fabricated microcarriers and compared the behavior of two homologous cell types in the microcarrier environment. The microcarrier environment highlighted the advantages of ADSCs and promoted the proliferation and migration of these cells. Then, ADSCs microtissues (ADSCs-MT) and BMSCs microtissues (BMSCs-MT) were fabricated using a three-dimensional dynamic culture system. In vitro and in vivo experiments verified that the cartilage regeneration ability of ADSCs-MT was significantly superior to that of BMSCs-MT. Transcriptomics revealed that ADSCs-MT showed significantly lower expression levels of ECM degradation, osteogenesis, and fibrocartilage markers. Finally, the protective effect of microtissues on inflammatory chondrocytes was validated. Overall, the ADSCs-MT constructed in this study achieved excellent cartilage regeneration and could be promising for the autologous application of cartilage microtissues.
由于其独特的结构,关节软骨的自我修复能力有限。微组织是可以模仿目标器官或组织功能的微小组织簇。单独使用细胞进行微组织构建通常会导致坏死核心的形成。然而,天然软骨的细胞外基质(ECM)可以提供结构支持,是微载体的理想来源。自体脂肪源性间充质干细胞(ADSCs)和骨髓间充质干细胞(BMSCs)在软骨组织工程中有着广泛的应用。在本研究中,我们制备了微载体,并比较了两种同源细胞类型在微载体环境中的行为。微载体环境突出了ADSCs的优势,促进了ADSCs的增殖和迁移。然后利用三维动态培养系统制备ADSCs微组织(ADSCs- mt)和BMSCs微组织(BMSCs- mt)。体外和体内实验证实ADSCs-MT的软骨再生能力明显优于BMSCs-MT。转录组学显示,ADSCs-MT的ECM降解、成骨和纤维软骨标志物的表达水平显著降低。最后,验证了微组织对炎性软骨细胞的保护作用。综上所述,本研究构建的ADSCs-MT具有良好的软骨再生效果,在软骨显微组织的自体应用方面具有广阔的前景。
{"title":"High paracrine activity of hADSCs cartilage microtissues inhibits extracellular matrix degradation and promotes cartilage regeneration","authors":"Wei Liu ,&nbsp;Hongyu Jiang ,&nbsp;Jiajie Chen ,&nbsp;Yue Tian ,&nbsp;Ying He ,&nbsp;Ying Jiao ,&nbsp;Yanjun Guan ,&nbsp;Zhibo Jia ,&nbsp;Yanbin Wu ,&nbsp;Cheng Huang ,&nbsp;Yiben Ouyang ,&nbsp;Wenjing Xu ,&nbsp;Jianhong Qi ,&nbsp;Jiang Peng ,&nbsp;Aiyuan Wang","doi":"10.1016/j.mtbio.2024.101372","DOIUrl":"10.1016/j.mtbio.2024.101372","url":null,"abstract":"<div><div>Due to its unique structure, articular cartilage has limited self-repair capacity. Microtissues are tiny tissue clusters that can mimic the function of target organs or tissues. Using cells alone for microtissue construction often results in the formation of necrotic cores. However, the extracellular matrix (ECM) of native cartilage can provide structural support and is an ideal source of microcarriers. Autologous adipose-derived mesenchymal stem cells (ADSCs) and bone marrow mesenchymal stem cells (BMSCs) are widely used in cartilage tissue engineering. In this study, we fabricated microcarriers and compared the behavior of two homologous cell types in the microcarrier environment. The microcarrier environment highlighted the advantages of ADSCs and promoted the proliferation and migration of these cells. Then, ADSCs microtissues (ADSCs-MT) and BMSCs microtissues (BMSCs-MT) were fabricated using a three-dimensional dynamic culture system. In vitro and <em>in vivo</em> experiments verified that the cartilage regeneration ability of ADSCs-MT was significantly superior to that of BMSCs-MT. Transcriptomics revealed that ADSCs-MT showed significantly lower expression levels of ECM degradation, osteogenesis, and fibrocartilage markers. Finally, the protective effect of microtissues on inflammatory chondrocytes was validated. Overall, the ADSCs-MT constructed in this study achieved excellent cartilage regeneration and could be promising for the autologous application of cartilage microtissues.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101372"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Materials Today Bio
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