Biomaterials research最新文献

{"title":"A Magnetic-Responsive Biomimetic Nanosystem Coated with Glioma Stem Cell Membranes Effectively Targets and Eliminates Malignant Gliomas.","authors":"Song Deng, Dekang Nie, Yue Huang, Yu Yang, Qianqian Liu, Zesheng Sun, Qiaoji Jiang, Yuejuan Ling, Ya Wen, Jiahua Qu, Jialiang Lin, Yi Wang, Rongqin Huang, Jinlong Shi","doi":"10.34133/bmr.0123","DOIUrl":"10.34133/bmr.0123","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is among the most challenging malignant brain tumors, making the development of new treatment strategies highly necessary. Glioma stem cells (GSCs) markedly contribute to drug resistance, radiation resistance, and tumor recurrence in GBM. The therapeutic potential of nanomaterials targeting GSCs in GBM urgently needs to be explored. A magnetic-responsive biomimetic nanosystem (FDPM), coated with glioma stem cell membranes (CMs), was designed for the targeted eradication of GSCs as well as their associated tumor cells. Identified nanobodies were extensively characterized with various assays. The application tests on nanomaterials were conducted in vitro and in vivo. The tumor-suppressive effects of the nanosystem were evaluated in vitro and in vivo. FDPM can be artificially directed under magnetic guidance while inheriting various biological functions from CM. Upon intravenous injection, FDPM was drawn to the tumor site by magnetic attraction, where it could cross the blood-brain barrier aided by CM. Its homologous targeting ability originates from active proteins on CM, enabling it to specifically target GSCs and related tumor cells. The encapsulated doxorubicin (DOX) within the nanoparticle then destroyed these tumor cells. FDPM demonstrated excellent biocompatibility and tumor-targeting efficiency, effectively targeting malignant gliomas initiated by GSCs. FDPM significantly reduced tumor cells, inhibited tumor growth, and notably extended the survival of glioma-bearing nude mice. The findings position FDPM as a promising nanoplatform to target GSCs and related tumor cells for improving the therapeutic effect of glioma.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0123"},"PeriodicalIF":8.1,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11676004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Throughput Screening of 3-Dimensional Co-culture Hair Follicle Mimetic Tissue with an Enhanced Extracellular Matrix for the Screening of Hair Growth-Promoting Compounds.","authors":"Huyen T M Pham, Hyo-Sop Kim, Duc Long Nguyen, Hyun Woo Joo, Min Kyu Kim, Young Kwan Sung, Minh Hung Vu, Heung Sik Hahm, Woo Jung Kim, Jae-Ho Kim, Hyun-Ji Park","doi":"10.34133/bmr.0125","DOIUrl":"10.34133/bmr.0125","url":null,"abstract":"<p><p>Hair follicle cells reside within a complex extracellular matrix (ECM) environment in vivo, where physical and chemical cues regulate their behavior. The ECM is crucial for hair follicle development and regeneration, particularly through epithelial-mesenchymal interactions. Current in vitro models often fail to replicate this complexity, leading to inconsistencies in evaluating hair loss treatments. Advanced 3-dimensional (3D) culture systems that better mimic in vivo ECM dynamics are needed for more effective therapeutic assessments. Here, we introduce a 3D co-culture system designed to replicate in vivo ECM dynamics. The system incorporates primary dermal papilla cells from human patients, co-cultured with neonatal keratinocytes. This platform facilitates uniform spheroid formation through cell sliding and aggregation, enabling the evaluation of approximately 60 spheroids per well. The model is optimized for high-throughput screening, allowing precise assessments of hair-loss-inducing compounds under consistent conditions. We successfully generated dermal papilla cell and keratinocyte spheroids that closely resemble the native ECM structure, providing an optimal microenvironment for studying hair follicle biology. The 3D co-culture model supported efficient spheroid formation with consistent cellular organization and polarization, along with enhanced ECM-related gene expression crucial for hair follicle regeneration. Uniform spheroid formation and reproducibility were demonstrated across experiments. Overall, the novel 3D co-culture system provides a robust platform for replicating in vivo-like ECM conditions, enabling effective assessment of potential hair loss treatments through epithelial-mesenchymal interactions. Its high-throughput capacity, combined with reproducibility and ease of use, makes it a valuable tool for screening therapeutic candidates and advancing hair loss treatment development.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0125"},"PeriodicalIF":8.1,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11675628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to \"An Ultrasoft and Flexible PDMS-Based Balloon-Type Implantable Device for Controlled Drug Delivery\".","authors":"Tausif Muhammad, ByungWook Park, Aseer Intisar, Minseok S Kim, Jin-Kyu Park, Sohee Kim","doi":"10.34133/bmr.0126","DOIUrl":"10.34133/bmr.0126","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.34133/bmr.0012.].</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0126"},"PeriodicalIF":8.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Biological Effects of Magnesium-Based Implants on the Skeleton and Their Clinical Implications in Orthopedic Trauma Surgery.","authors":"Elena Müller, Till Schoberwalter, Konrad Mader, Jan-Marten Seitz, Alexander Kopp, Anke Baranowsky, Johannes Keller","doi":"10.34133/bmr.0122","DOIUrl":"10.34133/bmr.0122","url":null,"abstract":"<p><p>Magnesium (Mg)-based implants have evolved as a promising innovation in orthopedic trauma surgery, with the potential to revolutionize the treatment of bone diseases, including osteoporotic fractures and bone defects. Available clinical studies mostly show excellent patient outcomes of resorbable Mg-based implants, without the need for subsequent implant removal. However, the occurrence of radiolucent zones around Mg-based implants seems to be a noticeable drawback for a more widespread clinical use. Mechanistically, both in vivo and in vitro studies demonstrated beneficial effects on the formation of new bone, a unique characteristic of Mg-based implants. In this regard, Mg has been shown to exert pleiotropic functions on osteogenic differentiation and migration of osteoblasts and their precursors. Additionally, collective evidence suggests that Mg-based implants promote angiogenesis in newly formed bone and exert immunomodulatory effects in the bone microenvironment. Likewise, Mg-based implants and their degradation products were shown to inhibit bone resorption by impairing osteoclastogenesis. The purpose of this review is to provide a state-of-the-art summary of the clinical and basic science evidence regarding the performance of currently used Mg-based implants. In addition to the status of in vivo and in vitro research and clinical applications, future challenges and perspectives of Mg-based orthopedic implants are discussed.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0122"},"PeriodicalIF":8.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Custom-Made Ce-Mn Bimetallic Nanozyme for the Treatment of Intervertebral Disc Degeneration by Inhibiting Oxidative Stress and Modulating Macrophage M1/M2 Polarization.","authors":"Jianwei Wu, Zhenhao Chen, Han Huang, Hongwei Wang, Xianghe Wang, Zian Lu, Haocheng Xu, Xiaosheng Ma, Feng Zeng, Hongli Wang","doi":"10.34133/bmr.0118","DOIUrl":"10.34133/bmr.0118","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IDD)-induced lower back pain (LBP) brings heavy burden worldwide. In the degenerated intervertebral disc, there is an increase in the accumulation of reactive oxygen species (ROS) and the infiltration of M1 macrophages, which leads to abnormal local inflammatory microenvironment and exacerbates IDD. In this study, we developed a novel injectable polyethylene glycol (PEG)-capped cerium ion-manganese ion (Ce-Mn) bimetallic nanozyme (CeMn-PEG) with strong ROS scavenging and M2-type macrophage polarizing abilities to efficiently alleviate IDD. In vitro experiments demonstrated that CeMn-PEG effectively scavenged excess ROS in both nucleus pulposus (NP) and RAW264.7 cells. In addition, we found that CeMn-PEG markedly protected NP cells from H₂O₂-induced overproduction of inflammatory cytokines, excessive cell apoptosis and autophagy, and imbalance between extracellular matrix (ECM) degradation. Moreover, CeMn-PEG induced macrophages to transition from the M1 phenotype to the M2 phenotype and the increased M2-type macrophages could alleviate H₂O₂-induced ECM degradation and cell apoptosis in NP cells. In a puncture-induced mouse IDD model, CeMn-PEG treatment could effectively ameliorate the progression of disc degeneration and mitigate puncture-induced mechanical hyperalgesia. Thus, our study demonstrated the effectiveness of CeMn-PEG as a novel treatment strategy for the treatment of IDD and a range of other inflammatory diseases.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0118"},"PeriodicalIF":8.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osseointegration-Related Exosomes for Surface Functionalization of Titanium Implants.","authors":"Boqiong Li, Huanming Chen, Ruiqiang Hang","doi":"10.34133/bmr.0124","DOIUrl":"10.34133/bmr.0124","url":null,"abstract":"<p><p>Despite that the clinical application of titanium-based implants has achieved great success, patients' own diseases and/or unhealthy lifestyle habits often lead to implant failure. Many studies have been carried out to modify titanium implants to promote osseointegration and implant success. Recent studies showed that exosomes, proactively secreted extracellular vesicles by mammalian cells, could selectively target and modulate the functions of recipient cells such as macrophages, nerve cells, endothelial cells, and bone marrow mesenchymal stem cells that are closely involved in implant osseointegration. Accordingly, using exosomes to functionalize titanium implants has been deemed as a novel and effective way to improve their osseointegration ability. Herein, recent advances pertaining to surface functionalization of titanium implants with exosomes are analyzed and discussed, with focus on the role of exosomes in regulating the functions of osseointegration-related cells, and their immobilization strategies as well as resultant impact on osseointegration ability.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0124"},"PeriodicalIF":8.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Polygonum multiflorum</i> Extracellular Vesicle-Like Nanovesicle for Skin Photoaging Therapy.","authors":"Junjia He, Luoqin Fu, Yeyu Shen, Yan Teng, Youming Huang, Xiaoxia Ding, Danfeng Xu, Hong Cui, Mingang Zhu, Jiahao Xie, Yue Su, Ting Li, Weitao Huang, Xiaozhou Mou, Qiong Bian, Yibin Fan","doi":"10.34133/bmr.0098","DOIUrl":"10.34133/bmr.0098","url":null,"abstract":"<p><p>Ultraviolet (UV) irradiation leads to the degradation of the extracellular matrix and collagen, thereby accelerating skin aging and imposing substantial psychological burden on patients. Current anti-aging strategies are limited and often associated with high costs or strong side effects. Plant-derived extracellular vesicle-like nanovesicles, with advantages such as natural availability and cost-effectiveness, show potential in anti-aging interventions. This study extracted extracellular vesicle-like nanovesicle from <i>Polygonum multiflorum</i> (PMELNVs) and systematically investigated their composition and metabolic pathways, further examining their efficacy and underlying mechanisms in combating photoaging. Results revealed the excellent antioxidative properties of PMELNVs, alleviating UV-induced oxidative stress, inhibiting matrix metalloproteinase production, reducing extracellular matrix degradation, promoting collagen synthesis, and ultimately exerting anti-photoaging effects. Additionally, safety assessments demonstrated favorable biocompatibility of PMELNVs. This study provides novel evidence supporting PMELNVs' ability to resist photoaging by reducing oxidative stress and enhancing collagen expression, thereby offering potential as a new natural therapeutic agent against skin photoaging and promising a safer and more effective local anti-aging strategy.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0098"},"PeriodicalIF":8.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Chondrogenic Differentiation of Electrically Primed Human Mesenchymal Stem Cells for the Regeneration of Osteochondral Defects.","authors":"Jongdarm Yi, Yujin Byun, Seong Soo Kang, Kyung Mi Shim, Kwangsik Jang, Jae Young Lee","doi":"10.34133/bmr.0109","DOIUrl":"10.34133/bmr.0109","url":null,"abstract":"<p><p><b>Background:</b> Mesenchymal stem cells (MSCs) offer a promising avenue for cartilage regeneration; however, their therapeutic efficacy requires substantial improvement. Cell priming using electrical stimulation (ES) is a promising approach to augmenting the therapeutic potential of MSCs and has shown potential for various regenerative applications. This study aimed to promote the ES-mediated chondrogenic differentiation of human MSCs and facilitate the repair of injured articular cartilage. <b>Methods:</b> MSCs were subjected to ES under various conditions (e.g., voltage, frequency, and number of repetitions) to enhance their capability of chondrogenesis and cartilage regeneration. Chondrogenic differentiation of electrically primed MSCs (epMSCs) was assessed based on gene expression and sulfated glycosaminoglycan production, and epMSCs with hyaluronic acid were transplanted into a rat osteochondral defect model. Transcriptomic analysis was performed to determine changes in gene expression by ES. <b>Results:</b> epMSCs exhibited significantly increased chondrogenic gene expression and sulfated glycosaminoglycan production compared with those in unstimulated controls. Macroscopic and histological results showed that in vivo epMSC transplantation considerably enhanced cartilage regeneration. Furthermore, ES markedly altered the expression of numerous genes of MSCs, including those associated with the extracellular matrix, the Wnt signaling pathway, and cartilage development. <b>Conclusion:</b> ES can effectively prime MSCs to improve articular cartilage repair, offering a promising strategy for enhancing the efficacy of various MSC-based therapies.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0109"},"PeriodicalIF":8.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11654951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highly Efficient Delivery of Novel MiR-13896 by Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Inhibits Gastric Cancer Progression by Targeting ATG2A-Mediated Autophagy.","authors":"Peipei Wu, Min Wang, Can Jin, Linli Li, Yuting Tang, Zhangfei Wang, Xianwen Wang, Wenrong Xu, Hui Qian","doi":"10.34133/bmr.0119","DOIUrl":"10.34133/bmr.0119","url":null,"abstract":"<p><p>Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related deaths worldwide. Despite recent advancements, clinical outcomes for GC remain unsatisfactory. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have shown promise in inhibiting tumor progression, but their role in GC, specifically human umbilical cord MSC-derived small EVs (hucMSC-sEVs), is not well understood. This study investigates the therapeutic potential of hucMSC-sEVs in GC treatment. We found that hucMSC-sEVs are captured by GC cells, substantially inhibiting their proliferation and inducing apoptosis. MiRNA sequencing revealed that hucMSC-sEVs were enriched with miRNAs having anticancer properties. Among these, miR-13896, a new miRNA, was identified as a potent inhibitor of GC cell proliferation and a promoter of apoptosis. Mechanistic studies revealed that miR-13896 targets and down-regulates the ATG2A-mediated autophagy pathway, suppressing GC cell growth and metastasis. Furthermore, we enriched hucMSC-sEVs with miR-13896 through electroporation. These engineered EVs specifically targeted tumor sites and significantly reduced GC cell growth and migration in vitro and in vivo. MiR-13896 emerged as a promising therapeutic target for GC. The delivery of miR-13896 via hucMSC-sEVs represents a novel and effective strategy for GC treatment, highlighting the potential of EV-based therapies to combat this malignancy.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0119"},"PeriodicalIF":8.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11654722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing Nanotechnology for Gout Therapy: Colchicine-Loaded Nanoparticles Regulate Macrophage Polarization and Reduce Inflammation.","authors":"Ning Zhang, Lanqing Zhao, Jinwei Li, Hongxi Li, Yu Chen","doi":"10.34133/bmr.0089","DOIUrl":"10.34133/bmr.0089","url":null,"abstract":"<p><p>Gout is a disease caused by hyperuricemia, characterized by inflammation reactions triggered by macrophage polarization. Colchicine is a commonly used drug for gout treatment, but its mechanism of action remains unclear. The aim of this study was to investigate the regulatory effect of colchicine on macrophage polarization to enhance the therapeutic effectiveness against gout inflammation. To accomplish this, a mouse model was established, and peripheral blood mononuclear cell samples were collected. Single-cell RNA sequencing was employed to reveal cellular heterogeneity and identify key genes. Molecular docking and experimental validation were performed to confirm the binding between the key genes and colchicine. Lentiviral intervention and biochemical indicator detection were conducted to assess the impact of key genes on gout mice. Additionally, the therapeutic effect of colchicine incorporated into neutrophil membrane-coated nanoparticles was investigated. The study found that macrophage polarization plays a critical role in gout, and AHNAK was identified as the key gene through which colchicine affects macrophage polarization. Lentiviral intervention to decrease AHNAK expression was shown to alleviate joint swelling in gout mice and regulate macrophage polarization. Colchicine encapsulated in R4F peptide-modified neutrophil membrane-coated Pluronic F127 nanoparticle (R4F-NM@F127) nanocarriers inhibited M1 macrophage polarization, induced M2 macrophage polarization, alleviated gout, and minimized toxicity to normal tissues. Colchicine suppressed M1 macrophage polarization and induced M2 macrophage polarization by binding to AHNAK protein, thereby alleviating gout. Colchicine incorporated into R4F-NM@F127 nanocarriers can serve as a targeted therapeutic drug to regulate macrophage polarization, alleviate gout, and reduce toxicity to normal tissues.</p>","PeriodicalId":93902,"journal":{"name":"Biomaterials research","volume":"28 ","pages":"0089"},"PeriodicalIF":8.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}