ACS Biomaterials Science & Engineering最新文献

{"title":"Data-Driven Framework for the Prediction of PEGDA Hydrogel Mechanics.","authors":"Yongkui Tang, Michal Levin, Olivia G Long, Claus D Eisenbach, Noy Cohen, Megan T Valentine","doi":"10.1021/acsbiomaterials.4c01762","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01762","url":null,"abstract":"<p><p>Poly(ethylene glycol) diacrylate (PEGDA) hydrogels are biocompatible and photo-cross-linkable, with accessible values of elastic modulus ranging from kPa to MPa, leading to their wide use in biomedical and soft material applications. However, PEGDA gels possess complex microstructures, limiting the use of standard polymer theories to describe them. As a result, we lack a foundational understanding of how to relate their composition, processing, and mechanical properties. To address this need, we use a data-driven approach to develop an empirical predictive framework based on high-quality data obtained from uniaxial compression tests and validated using prior data found in the literature. The developed framework accurately predicts the hydrogel shear modulus and the strain-stiffening coefficient using only synthesis parameters, such as the molecular weight and initial concentration of PEGDA, as inputs. These results provide simple and reliable experimental guidelines for precisely controlling both the low-strain and high-strain mechanical responses of PEGDA hydrogels, thereby facilitating their design for various applications.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue-Safe Low-Temperature Plasma Treatment for Effective Management of Mature Peri-Implantitis Biofilms on Titanium Surfaces.","authors":"Beatriz H D Panariello, Giovanna C Denucci, Caroline C Tonon, George J Eckert, Lukasz Witek, Vasudev V Nayak, Paulo G Coelho, Simone Duarte","doi":"10.1021/acsbiomaterials.4c01413","DOIUrl":"10.1021/acsbiomaterials.4c01413","url":null,"abstract":"<p><p>The unique screw-shape design and microstructure of implants pose a challenge for mechanical debridement in removing biofilms. Biofilms exhibit increased resistance to antimicrobials relative to single planktonic cells, emphasizing the need for effective biofilm removal during periodontal therapy for peri-implantitis treatment. To tackle this issue, our team evaluated the effectiveness of low-temperature plasma (LTP) for disinfecting titanium discs contaminated with multispecies biofilms associated with peri-implantitis, specifically focusing on biofilms matured for 14 and 21 days as well as biofilms that had formed on Straumann^Ⓡ Ti-SLA implants for 21 days. The biofilms included <i>Actinomyces naeslundii</i>, <i>Porphyromonas gingivalis</i>, <i>Streptococcus oralis</i>, and <i>Veillonella dispar</i>, which were grown in anaerobic conditions. These biofilms were subjected to LTP treatment for 1, 3, and 5 min, using distances of 3 or 10 mm from the LTP nozzle to the samples. Control groups included biofilms formed on Ti discs or implants that received no treatment, exposure to argon flow at 3 or 10 mm of distance for 1, 3, or 5 min, application for 1 min of 14 μg/mL amoxicillin, 140 μg/mL metronidazole, or a blend of both, and treatment with 0.12% chlorhexidine (CHX) for 1 min. For the implants, 21-day-old biofilms were treated with 0.12% CHX 0.12% for 1 min and LTP for 1 min at a distance of 3 mm for each quadrant. Biofilm viability was assessed through bacterial counting and confocal laser scanning microscopy. The impact of LTP was investigated on reconstituted oral epithelia (ROE) contaminated with <i>P. gingivalis</i>, evaluating cytotoxicity, cell viability, and histology. The results showed that a 1 min exposure to LTP at distances of 3 or 10 mm significantly lowered bacterial counts on implants and discs compared to the untreated controls (<i>p</i> < 0.017). LTP exposure yielded lower levels of cytotoxicity relative to the untreated contaminated control after 12 h of contamination (<i>p</i> = 0.038), and cell viability was not affected by LTP (<i>p</i> ≥ 0.05); thus, LTP-treated samples were shown to be safe for tissue applications, with low cytotoxicity and elevated cell viability post-treatment, and these results were validated by qualitative histological analysis. In conclusion, the study's results support the effectiveness of 1 min LTP exposure in successfully disinfecting mature peri-implantitis multispecies biofilms on titanium discs and implants. Moreover, it validated the safety of LTP on ROE, suggesting its potential as an adjunctive treatment for peri-implantitis.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7647-7656"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outer Membrane Vesicle-Cancer Hybrid Membrane Coating Indocyanine Green Nanoparticles for Enhancing Photothermal Therapy Efficacy in Tumors.","authors":"Jing Zhao, Bo Yu, Lujing Li, Sihua Guo, Xuan Sha, Waner Ru, Guo-Qing Du, Jing-Yi Xue","doi":"10.1021/acsbiomaterials.4c01251","DOIUrl":"10.1021/acsbiomaterials.4c01251","url":null,"abstract":"<p><p>Cell membrane-coated nanomaterials are increasingly recognized as effective in cancer treatment due to their unique benefits. This study introduces a novel hybrid membrane coating nanoparticle, termed cancer cell membrane (CCM)-outer membrane vesicle (OMV)@Lip-indocyanine green (ICG), which combines CCMs with bacterial OMV to encapsulate ICG-loaded liposomes. Comprehensive analyses were conducted to assess its physical and chemical properties as well as its functionality. Demonstrating targeted delivery capabilities and good biocompatibility, CCM-OMV@Lip-ICG nanoparticles showed promising photothermal and immunotherapeutic effects in tumor models. By inducing hyperthermia-induced tumor therapy and bolstering antitumor immunity, CCM-OMV@Lip-ICG nanoparticles exhibit a synergistic therapeutic effect, providing a new perspective for the management of cancer.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7619-7631"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogels Treat Atopic Dermatitis by Transporting Marine-Derived miR-100-5p-Abundant Extracellular Vesicles.","authors":"Zijie Wu, Lei He, Linhong Yan, Baoyi Tan, Lihua Ma, Guoli He, Zhenqing Dai, Ruikun Sun, Chengyong Li","doi":"10.1021/acsbiomaterials.4c01649","DOIUrl":"10.1021/acsbiomaterials.4c01649","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a prevalent skin disorder worldwide. However, many AD medications are unsuitable for long-term use due to low therapeutic efficacy and side effects. Extracellular vesicles (EVs) extracted from <i>Pinctada martensii</i> mucus have demonstrated therapeutic efficacy in AD. It is hypothesized that EVs may exert their activity on mammalian cells through their specific contents. In this study, we analyzed the results of miRNA sequencing of the EVs and investigated the potency of highly expressed miR-100-5p in treating AD. To enhance the therapeutic efficiency of the EVs in AD, we developed oxidized sodium alginate (OSA)-carboxymethyl chitosan (CMCS) self-cross-linked hydrogels as a vehicle to deliver the EVs to BALB/c mice with dermatitis. The miR-100-5p in EVs exhibited a favorable anti-inflammatory function, while the hydrogels provided enhanced skin residency. Additionally, its efficacy in inflammation inhibition and collagen synthesis was demonstrated in in vivo experiments. Mechanistically, miR-100-5p in EVs exerted anti-inflammatory effects by inhibiting the expression of FOXO3, consequently suppressing the activation of the downstream NLRP3 signaling pathway. This study underscores the significance of utilizing OSA-CMCS hydrogels as a vehicle for delivering miR-100-5p in <i>P. martensii</i> mucus-derived EVs for the treatment of AD.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7667-7682"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Piezo1 Mediates Glycolysis-Boosted Pancreatic Ductal Adenocarcinoma Chemoresistance within a Biomimetic Three-Dimensional Matrix Stiffness.","authors":"Haopeng Pan, Xue Zhang, Shajun Zhu, Biwen Zhu, Di Wu, Jiashuai Yan, Xiaoqi Guan, Yan Huang, Yahong Zhao, Yumin Yang, Yibing Guo","doi":"10.1021/acsbiomaterials.4c01319","DOIUrl":"10.1021/acsbiomaterials.4c01319","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a very low 5-year survival rate, which is partially attributed to chemoresistance. Although the regulation of chemoresistance through biochemical signaling is well-documented, the influence of three-dimensional (3D) matrix stiffness is poorly understood. In this study, gelatin methacrylate (GelMA) hydrogels were reconstructed with stiffnesses spanning the range from normal to cancerous PDAC tissues, which are termed as the soft group and stiff group. The PDAC cell lines (Mia-PaCa2 and CFPAC-1) encapsulated in the stiff group displayed a chemoresistance phenotype and were prominent against gemcitabine. RNA-sequencing and bioinformatics analysis indicated that glycolysis was apparently enriched in the stiff group <i>versus</i> the soft group, which was also validated through assays of glucose uptake, lactate production, and the expression of GLUT2, HK2, and LDHA. A rescue assay with 2-deoxy-d-glucose and <i>N</i>-acetylcysteine demonstrated that glycolysis is involved in chemoresistance. Furthermore, the expression of Piezo1 and the content of Ca²⁺ were elevated in the stiff group. The addition of Yoda1 (Piezo1 agonist) in the soft group promoted glycolysis, whereas in the stiff group, treatment with GsMTx4 (Piezo1 inhibitor) inhibited glycolysis, which showcased that Piezo1 participated in 3D matrix stiffness-induced glycolysis. Taken together, Piezo1-mediated glycolysis was involved in PDAC chemoresistance triggered by the 3D matrix stiffness. Our study sheds light on the mechanism underlying chemoresistance in PDAC from the perspective of 3D mechanical cues.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7632-7646"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of Bone Defects and Nonunion via Novel Delivery Mechanisms, Growth Factors, and Stem Cells: A Review.","authors":"Quinn T Ehlen, Joseph P Costello, Nicholas A Mirsky, Blaire V Slavin, Marcelo Parra, Albert Ptashnik, Vasudev Vivekanand Nayak, Paulo G Coelho, Lukasz Witek","doi":"10.1021/acsbiomaterials.4c01279","DOIUrl":"10.1021/acsbiomaterials.4c01279","url":null,"abstract":"<p><p>Bone nonunion following a fracture represents a significant global healthcare challenge, with an overall incidence ranging between 2 and 10% of all fractures. The management of nonunion is not only financially prohibitive but often necessitates invasive surgical interventions. This comprehensive manuscript aims to provide an extensive review of the published literature involving growth factors, stem cells, and novel delivery mechanisms for the treatment of fracture nonunion. Key growth factors involved in bone healing have been extensively studied, including bone morphogenic protein (BMP), vascular endothelial growth factor (VEGF), and platelet-derived growth factor. This review includes both preclinical and clinical studies that evaluated the role of growth factors in acute and chronic nonunion. Overall, these studies revealed promising bridging and fracture union rates but also elucidated complications such as heterotopic ossification and inferior mechanical properties associated with chronic nonunion. Stem cells, particularly mesenchymal stem cells (MSCs), are an extensively studied topic in the treatment of nonunion. A literature search identified articles that demonstrated improved healing responses, osteogenic capacity, and vascularization of fractures due to the presence of MSCs. Furthermore, this review addresses novel mechanisms and materials being researched to deliver these growth factors and stem cells to nonunion sites, including natural/synthetic polymers and bioceramics. The specific mechanisms explored in this review include BMP-induced osteoblast differentiation, VEGF-mediated angiogenesis, and the role of MSCs in multilineage differentiation and paracrine signaling. While these therapeutic modalities exhibit substantial preclinical promise in treating fracture nonunion, there remains a need for further research, particularly in chronic nonunion and large animal models. This paper seeks to identify such translational hurdles which must be addressed in order to progress the aforementioned treatments from the lab to the clinical setting.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7314-7336"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local Stiffness Measurement of Hepatic Steatosis Model Liver Organoid by Fluorescence Imaging-Assisted Probe Indentation.","authors":"Dae-Seop Shin, Myung Jin Son, Myungae Bae, Hyunwoo Kim","doi":"10.1021/acsbiomaterials.4c01242","DOIUrl":"10.1021/acsbiomaterials.4c01242","url":null,"abstract":"<p><p>Mechanical stiffness of liver organoid is a key indicator for the progress of hepatic steatosis. Probe indentation is a noninvasive methodology to measure Young's modulus (YM); however, the inhomogeneous nature of the liver organoid induces measurement uncertainty requiring a large number of indentations covering a wide scanning area. Here, we demonstrate that lipid-stained fluorescence imaging-assisted probe indentation significantly reduces the number of measurements by specifying the highly lipid-induced area. Lipid-stained hepatic steatosis model liver organoid shows broad fluorescence distributions that are spatially correlated with a decreased YM on a lipid-filled region with bright fluorescence compared with that measured on a blank region with dark fluorescence. The organoid viability remained robust even after exposure to an ambient condition up to 6 h, showing that probe indentations can be noninvasive methods for liver organoid stiffness measurements.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7386-7393"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decellularized Extracellular Matrix Scaffolds: Recent Advances and Emerging Strategies in Bone Tissue Engineering.","authors":"Yunyang Li, Jingwen Wu, Peilin Ye, Yilin Cai, Mingfei Shao, Tong Zhang, Yanchuan Guo, Sujuan Zeng, Janak L Pathak","doi":"10.1021/acsbiomaterials.4c01764","DOIUrl":"10.1021/acsbiomaterials.4c01764","url":null,"abstract":"<p><p>Bone tissue engineering (BTE) is a complex biological process involving the repair of bone tissue with proper neuronal network and vasculature as well as bone surrounding soft tissue. Synthetic biomaterials used for BTE should be biocompatible, support bone tissue regeneration, and eventually be degraded in situ and replaced with the newly generated bone tissue. Recently, various forms of bone graft materials such as hydrogel, nanofiber scaffolds, and 3D printed composite scaffolds have been developed for BTE application. Decellularized extracellular matrix (DECM), a kind of natural biological material obtained from specific tissues and organs, has certain advantages over synthetic and exogenous biomaterial-derived bone grafts. Moreover, DECM can be developed from a wide range of biological sources and possesses strong molding abilities, natural 3D structures, and bioactive factors. Although DECM has shown robust osteogenic, proangiogenic, immunomodulatory, and bone defect healing potential, the rapid degradation and limited mechanical properties should be improved for bench-to-bed translation in BTE. This review summarizes the recent advances in DECM-based BTE and discusses emerging strategies of DECM-based BTE.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7372-7385"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surface Engineered Osteoblast-Extracellular Vesicles Serve as an Efficient Carrier for Drug and Small RNA to Actively Target Osteosarcoma.","authors":"Sasmita Samal, Gyanendra Prasad Panda, Sharmishtha Shyamal, Kapilash Das, Mamoni Dash","doi":"10.1021/acsbiomaterials.4c00952","DOIUrl":"10.1021/acsbiomaterials.4c00952","url":null,"abstract":"<p><p>Osteosarcoma (OS) is a rare malignant tumor that affects soft tissue and has high rates of lung metastasis and mortality. The primary treatments for OS include preoperative chemotherapy, surgical resection of the lesion, and postoperative chemotherapy. However, OS chemotherapy presents critical challenges related to treatment toxicity and multiple drug resistance. To address these challenges, nanotechnology has developed nanosystems that release drugs directly to OS cells, reducing the drug's toxicity. Extracellular vesicles (EVs) are nanosized lipid-bilayer bound vesicles that act as cell-derived vehicles and drug delivery systems for several cancers. This study aims to utilize EVs for OS management by co-delivering Hdac1 siRNA and zoledronic acid (zol). The EVs' surface is modified with folic acid (FA) and their targeting ability is compared to that of native EVs. The results showed that the EVs' targeting ability depends on the parent cell source, and FA conjugation further enhanced it. Furthermore, EVs were used as the carrier for co-loading drug (zol) and small RNA (Hdac-1). This approach of using surface engineered EVs as carriers for cargo loading and delivery can be a promising strategy for osteosarcoma management.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7466-7481"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Hydroxyapatite Nanowires on Formation and Bioactivity of Osteoblastic Cell Spheroid.","authors":"Hanjing Li, Hongwei Chen, Chunyuan Du, Yucheng Liu, Li Wan, Fanrong Ai, Kui Zhou","doi":"10.1021/acsbiomaterials.4c01159","DOIUrl":"10.1021/acsbiomaterials.4c01159","url":null,"abstract":"<p><p>Compared with traditional high-density cell spheroids, which are more prone to core necrosis, nanowires effectively improve the biological activity of core cells in spheroids, emanating more innovations for optimizing the internal cell survival environment and providing differentiation signals. In this study, hydroxyapatite nanowires (HAW), which provide numerous material exchange channels for internal cells by interpenetrating into cell spheroids, were added to osteoblast precursor (MC3T3-E1) cell spheroids. HAW, synthesized using the hydrothermal method, was used as a regulatory material to prepare uniformly sized 3D composite spheroids with good biological activity. Subsequently, material characterization and biocompatibility tests were performed on HAW, and the biological activity and osteogenic differentiation ability of the cell spheroids were tested. Notably, in 2D coculture, HAW displayed a certain attraction to MC3T3-E1 cells and promoted cell aggregation toward it. The content of HAW determined whether composite cell spheroids can form aggregated spherical structures, and incorporation of HAW alleviated core necrosis and enhanced the osteogenic phenotype. In summary, these findings indicate that the prepared HAW-bone cell composite spheroids can potentially be used as building blocks for the construction of large high-density biomimetic tissues and organoids using 3D bioprinting technology.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7413-7428"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}