International Journal of Bioprinting最新文献

{"title":"Advancements in 3D bioprinting for nanoparticle evaluation: Techniques, models, and biological applications","authors":"Moon Sup Yoon, Jae Min Lee, Min Jeong Jo, Su Jeong Kang, Myeong Kyun Yoo, So Yeon Park, Ji-Hyun Kang, Chan-Su Park, Chun-Woong Park, Jin-Seok Kim, A. Bernardos, Vicente Martí-Centelles, Ramón Martínez-Máñez, Dae Hwan Shin","doi":"10.36922/ijb.4273","DOIUrl":"https://doi.org/10.36922/ijb.4273","url":null,"abstract":"Three-dimensional bioprinting technology has opened new possibilities for nanoparticle evaluation. This review discusses the latest research trends using various disease models created through 3D bioprinting for biological evaluation of nanoparticles. The focus is on tumor models, vessel models, and skin models. In tumor models, evaluations include antitumor effects, gene expression analysis, and cytotoxicity comparisons between 2D and 3D models. Vessel models assess restenosis prevention, ischemic repair, and vascular regeneration. Skin models investigate nanoparticle toxicity, drug release, and transdermal penetration. These studies highlight the versatility of 3D bioprinting in replicating complex biological environments, enabling more accurate nanoparticle testing. The use of various bioinks and cell types enhances the relevance of in vitro findings. The integration of nanoparticles with 3D bioprinted models shows significant potential in advancing therapeutic strategies, including cancer treatment, vascular repair, and drug delivery systems. Overall, this comprehensive review underscores the importance of 3D bioprinting as an innovative platform for nanoparticle research, bridging the gap between traditional 2D cell cultures and in vivo studies, and contributing to the development of nanomedicines and personalized medical treatments, providing selected examples to illustrate the concepts.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141925315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methacrylic anhydride-assisted one-step in-situ extrusion 3D bioprinting of collagen hydrogels for enhanced full-thickness skin regeneration","authors":"Xiaxia Yang, Linyan Yao, Wenhua Li, Xiaodi Huang, Na Li, Jianxi Xiao","doi":"10.36922/ijb.4069","DOIUrl":"https://doi.org/10.36922/ijb.4069","url":null,"abstract":"Full-thickness skin injuries cause extended inflammation, compromised angiogenesis, and protracted wound healing, presenting considerable health risks. Herein, we introduce an innovative technique utilizing methacrylic anhydride (MA)-enhanced, one-step in-situ extrusion 3D bioprinting of collagen hydrogels, specifically engineered for the effective repair of full-thickness skin injuries. This method capitalizes on the inherent bioactivity of collagen, surmounting its mechanical constraints via a streamlined, one-step extrusion process enabled by MA. The resultant biomaterial ink, an optimized mix of collagen, MA, and photoinitiator, demonstrates superior printability, mechanical robustness, and stability, making it an ideal candidate for direct application onto wound sites. The bioprinted collagen scaffolds exhibit improved mechanical strength, reduced swelling, and enhanced resistance to enzymatic degradation, providing a durable matrix for cell proliferation and tissue in-growth. In vitro assessments reveal that the scaffolds support human foreskin fibroblast adhesion, proliferation, and migration, creating a conducive environment for skin regeneration. In vivo evaluations, conducted using a rat full-thickness skin injury model, further validate the scaffold's efficacy in promoting rapid and orderly tissue repair, characterized by accelerated re-epithelialization and organized collagen deposition. This MA-enhanced, in-situ extrusion 3D bioprinting technique generates collagen hydrogel scaffolds that significantly accelerate wound healing, offering promising advancements in tissue engineering and regenerative medicine.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141922697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteocytic PGE2 receptors EP2/4 signaling create a physiological osteogenic microenvironment in polycaprolactone 3D module","authors":"Jingjing Chen, Qiuling Guo, Jinling Zhang, Ying Zhang, Yangxi Liu, Pengtao Wang, Chengzhu Zhao, Linda F Bonewald, Xiaolin Tu","doi":"10.36922/ijb.3959","DOIUrl":"https://doi.org/10.36922/ijb.3959","url":null,"abstract":"3D bioprinting is a focused field in orthopedics, and its application with physiological osteogenic microenvironments (POME) is a prerequisite for authentic bone reconstruction. Mechanical stimulation produces PGE2 in mechanosensory osteocytes, but it is still unclear whether osteocytic PGE2 is a POME. PGE2 is an inducer of osteogenesis by acting on bone marrow stromal cells through its receptors EP2/EP4 to initiate osteogenic differentiation and mineralization. Unfortunately, clinical trials of PGE2 have shown side effects, including fever and drowsiness, so targeting the PGE2 receptor on specific tissues can avoid side effects. Here, we show that MLO-Y4 osteocytes treated with EP2/EP4 agonists for 24 h develop the functions of promoting osteogenic differentiation and mineralization while inhibiting adipogenesis of the stromal cell line ST2 and inducing tubule formation and angiogenic marker expression in HUVEC cells. Mechanistically, activation of the PGE2 signaling pathway in osteocytes appears to have autocrine effects by inducing the expression of the EP2 and EP4 receptors and COX-2 (Ptgs2), further auto-amplifying PGE2 signaling. PGE2 produced by the treated MLO-Y4 cells appears responsible for osteogenesis in addition to other unknown factors. MLO-Y4 and ST2 cells were incorporated into POME 3D constructs with greater than 95% viability within 7 days. Treatment of osteocytes with a PGE2 receptor agonist lineally proliferates ST2 cells, enhances the expression of osteoblast markers and mineralization. Due to 3D bioprinting being the closest model to in vivo research, these data showed that osteocytic PGE2 receptor signaling is a safe and mild POME with great potential for translational applications.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141926085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimental and numerical approaches for optimizing conjunction area design to enhance switching efficiency in single-nozzle multi-ink bioprinting systems","authors":"Mitsuyuki Hidaka, Masaru Kojima, Colin Zhang, Yasunori Okano, Shinji Sakai","doi":"10.36922/ijb.4091","DOIUrl":"https://doi.org/10.36922/ijb.4091","url":null,"abstract":"Three-dimensional (3D) bioprinting has emerged as a promising technology in the field of tissue engineering. Notably, the advancement of multi-ink printing technology is crucial for further progress in 3D bioprinting. In this study, we developed a single-nozzle system with multiple inlets for multi-ink bioprinting that achieves high switching efficiency through a combination of numerical and experimental approaches. This single-nozzle system demonstrates the potential for higher-resolution printing and quicker ink switching compared with multi-nozzle printing systems. In general, inks used in bioprinting have low viscosity (<10 Pa・s); however, their behaviors inside a single nozzle have not been thoroughly investigated. Initially, we conducted numerical simulations to analyze fluid behavior within single nozzles, focusing on the junction of multiple ink inlets, to propose an advanced nozzle design. We proposed a novel index, Se, for evaluating the switching behavior of the bioink inside the single nozzle. Numerical simulation results showed that the nozzle design and combinations of inks affected Se. In addition, subsequent experimental analysis confirmed the consistency of the simulation results. The proposed design, developed using simulations, featured a single nozzle with enhanced switching efficiency, demonstrating a smaller transition length compared with that of conventional single nozzles or T-junction nozzles in printing line structures of different viscous inks. This is the first study to employ numerical simulation in designing a single nozzle with multiple inlets to switch ink in multi-ink bioprinting. This methodology will broaden the potential of single nozzles for high-resolution printing in bioprinting applications.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141926055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and fabrication of anisotropic SiO2 gyroid bioscaffolds with tunable properties","authors":"K. Yeung, Chi-Yeung Mang, Quan-Jing Mei, Chi Ho Wong, Chak-Yin Tang, Xin Zhao, Wing-Cheung Law, G. Tsui, Zhenjia Huang","doi":"10.36922/ijb.3609","DOIUrl":"https://doi.org/10.36922/ijb.3609","url":null,"abstract":"This paper introduces a mathematical approach and additive manufacturing process to customize the mechanical properties of sheet gyroid bioscaffolds and mimicking the intricate architecture of natural bone. By defining the parameters of the level-set equation, scaffolds with spatially controlled porosity and anisotropic properties can be fabricated though digital light processing and microwave heating. A new susceptor-assisted hybrid pyrolysis-sintering process was developed, resulting in a significant enhancement in quality and mechanical properties of the three-dimensional (3D)-printed ceramic compared to conventional methods. The enhancements are originated from the improved densification, accelerated sintering kinetics, promotion of cristobalite phase transformation, and reduced defect volume under microwave heating. Sheet gyroid scaffolds with radially graded porosity and anisotropic properties were fabricated. Despite the porosity distribution, an increase in the unit cell’s aspect ratio amplified the anisotropic mechanical properties. This was also accompanied by a slight decrease in cell proliferation efficiency possibly due to variations in Gaussian curvatures.  ","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141927717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photoacoustic imaging for three-dimensional bioprinted constructs","authors":"Donghyeon Oh, H. Choi, Chulhong Kim, Jinah Jang","doi":"10.36922/ijb.3448","DOIUrl":"https://doi.org/10.36922/ijb.3448","url":null,"abstract":"Bioimaging is used to inspect the successful growth and functional differentiation of cells in printed biomaterials, which are ultimately finalized into functional artificial tissues capable of replacing native tissues. While optical bioimaging techniques are commonly utilized, the current trend in three-dimensional (3D) bioprinting towards replicating complex 3D microarchitectures poses a challenge for conventional optical imaging techniques in providing clear cross-sectional images due to the opaque nature of tissue. Consequently, these limitations necessitate lengthy and destructive preparation processes, which are associated with sacrificing cell viability and damaging the bioprinted material. Photoacoustic imaging (PAI) is a versatile imaging technique that extends the advantages of the optical bioimaging technique to undiscovered depths enabled by its acoustic hybridity, making itself a promising tool for non-destructive imaging of 3D bioprinted constructs. In this review, we introduce the flexible spectral contrasts provided by PAI, which are potentially applicable to 3D-bioprinted constructs, and summarize bioprinting studies that functionally implement PAI for in vitro and in vivo assessments. Finally, we provide an outlook on practical considerations for the more complete integration of these two fields, anticipating more fruitful discoveries as bioprinting advances towards more complex hierarchies.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141812127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D-bioprinted gelatin methacryloyl hydrogel culture system emulating the oviduct environment for enhanced preimplantation embryo development","authors":"Yun Dong Koo, Min-Hee Kang, Dahong Kim, Min Jeong Cho, Yu Jin Kim, JuYi Jang, Seon Ju Yeo, Geehong Kim, Su A Park, Jae Ho Lee","doi":"10.36922/ijb.3346","DOIUrl":"https://doi.org/10.36922/ijb.3346","url":null,"abstract":"Oviducts have specific biomechanical properties that support fertilization and preimplantation embryo development, both of which are essential for successful pregnancy. However, conventional plastic-based human embryo culture does not recapitulate the biomechanical environment of the oviduct. Therefore, oviduct mimic culture systems that accurately emulate biophysical conditions for reproductive cells are a significant unmet clinical need. In the present study, we designed a three-dimensional (3D)-bioprinted optimal soft hydrogel system that accurately mimics the oviduct environment and investigated signaling factors during embryo development. We developed an oviduct tube-mimic hydrogel culture dish using gelatin methacryloyl (GelMA) 3D-bioprinted hydrogel. Quantitative assessment of hydrogel mechanical properties depended on the stiffness of the GelMA 3D-bioprinted hydrogel. Embryo quality was evaluated based on cleavage speed and blastocyst ratio on the GelMA hydrogel. Whole-transcriptome next-generation sequencing (NGS) analysis of embryos was used to identify biomechanical signaling factors. Our findings revealed that 10 kPa GelMA hydrogel culture conditions performed better with respect to development speed, blastocyst ratio, and hatching ratio than the control condition. Whole transcriptome NGS revealed up-regulation of mRNA processing genes and protein transport genes by the 7 and 10 kPa hydrogels. Furthermore, the inner cell mass and the number of Oct4+ cells were significantly higher in blastocysts cultured on 10 kPa hydrogel dishes than in those cultured on conventional hard plastic dishes. These findings demonstrate that optimized oviduct-mimic hydrogel-based 3D GelMA culture dishes could improve in vitro embryo development. Hence, 3D GelMA culture dishes may be useful as human embryo culture systems for assisted reproductive techniques.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141814445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":" A functionally graded gyroid-type three-periodic minimal surface framework applied to implant-supported fixed complete dentures","authors":"Jiwei Ren, Renkai Huang, linqin Huang, Shaoying Yang, Chunrong Pan, Yuchun Sun, Sukun Tian, Xuehua Wu, Dongsheng Wang, Youwen Yang","doi":"10.36922/ijb.3453","DOIUrl":"https://doi.org/10.36922/ijb.3453","url":null,"abstract":"Titanium alloy, particularly Ti6Al4V, is commonly used for constructing the framework of implant-supported fixed complete dentures (IFCDs) but exhibits poor specific strength and impact toughness. Three-periodic minimal surface (TPMS) porous structures have the advantages of high specific strength, lightweight, and shock and energy absorption. Therefore, the functionally graded TPMS porous structure was adopted to design the framework for IFCDs in this study. Nine types of TPMS-based lattice structures with radial gradient variations were designed. Finite element analysis and experimental results indicate that the relative density increases outward and the cell size decreases outward from the center. The B-I porous structure has the highest strength and impact toughness compared to other gradient porous structure types. Moreover, the IFCD framework, utilizing the B-I porous structure, exhibited a 50% reduction in weight compared to the solid framework. When compared to the hollow framework with the same weight, the B-I framework demonstrated a 42.81% lower maximum equivalent stress under normal chewing conditions without undergoing plastic deformation. Therefore, the B-I framework meets the mechanical performance requirements for daily chewing and exhibits superior mechanical properties over conventional structures.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141821403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the effect of pregabalin on neuronal development using ultrashort self-assembling peptides: Assessing 3D neuronal cultures with high throughput robotic 3D bioprinting","authors":"Walaa F. Alsanie, Sherin Abdelrahman, M. Alhomrani, Alexander U. Valle-Pérez, Ebtisam Abdulah Alosimi, Hamza Habeeballah, Heba A. Alkhatabi, Raed I. Felimban, Abdulhakeem S. Alamri, Abdulaziz Alsharif, Bassem M. Raafat, Yusuf S. Althobaiti, Ahmed Gaber, Charlotte A. E. Hauser","doi":"10.36922/ijb.3010","DOIUrl":"https://doi.org/10.36922/ijb.3010","url":null,"abstract":"Pregabalin is a widely prescribed drug for various neurological disorders, yet its effects on embryonic cortical neuron development when given to pregnant women remain inadequately explored. In this study, we employed advanced three-dimensional (3D) culturing and in-house developed high-throughput robotic 3D bioprinting technologies to evaluate their potential in neuropharmacology applications, using pregabalin as a model compound. Using a robotic 3D bioprinter and tetrameric IIZK peptide hydrogel as bioink, we created constructs with pregabalin-treated and untreated primary mouse embryonic cortical neurons. This setup allowed us to study the drug’s effects on cell viability, expression of neuronal markers, and neuron development. Our comparative analysis between 2D and 3D peptide-based cell culture models revealed that at a therapeutic concentration of 10 μM, pregabalin does not affect neuronal viability or the morphogenesis of cortical neurons. However, it significantly alters adenosine triphosphate (ATP) release, suggesting potential disruptions in mitochondrial function. Moreover, gene expression analysis of key genes involved in the development of the forebrain and the differentiation and maturation of neurons revealed significant alterations, including the downregulation of Dlx2, Nhlh2, Otp, and Gad67. These findings, together with observed alterations in neuronal activity and oscillations, emphasize the complex impact of pregabalin on neuronal development and function. They highlight the necessity for comprehensive clinical evaluations of its use during pregnancy. Furthermore, our research demonstrates the feasibility and value of integrating 3D cultures with high-throughput 3D bioprinting in neuropharmacology, opening new avenues for investigating drug effects on neuronal development and function, and contributing to safer clinical practices.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141824829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D-printed Mg-substituted hydroxyapatite/ gelatin methacryloyl hydrogels encapsulated with PDA@DOX particles for bone tumor therapy and bone tissue regeneration","authors":"Shangsi Chen, Yue Wang, Junzhi Li, Haoran Sun, Ming-Fung Francis Siu, Shenglong Tan","doi":"10.36922/ijb.3526","DOIUrl":"https://doi.org/10.36922/ijb.3526","url":null,"abstract":"The development of bifunctional scaffolds for clinical applications, aimed at preventing tumor recurrence and promoting bone tissue regeneration simultaneously at the surgical site, is imperative in repairing bone tumor-related defects. In the current study, Mg-substituted hydroxyapatite (MgHAp) nanocomposites were synthesized via a biomineralization process. Doxorubicin hydrochloride (DOX), an anticancer drug, was incorporated in polydopamine (PDA) particles to synthesize PDA@DOX particles. MgHAp/gelatin methacryloyl (GelMA) hydrogels encapsulated with PDA@DOX particles were designed and fabricated to construct MgHAp/GelMA-PDA@DOX hydrogels via 3D printing. The 3D-printed MgHAp/GelMA-PDA@DOX hydrogels exhibited antitumor synergy by providing combined chemotherapy and phototherapy for bone tumor cell ablation. The hydrogels showed a good photothermal effect and could induce hyperthermia upon irradiation with an 808 nm near-infrared (NIR) laser. Moreover, MgHAp/GelMA-PDA@DOX hydrogels could release DOX sustainably and controllably. In vitro experiments demonstrated that 3D-printed MgHAp/GelMA-PDA@DOX hydrogels could effectively eradicate MG63 cells through the synergy of induced hyperthermia and DOX release. Furthermore, due to the sustained release of Mg2+, 3D-printed MgHAp/GelMA-PDA@DOX hydrogels could promote the proliferation of rat bone marrow-derived mesenchymal stem cells and facilitate alkaline phosphatase activity and the expression of osteogenic genes, such as osteocalcin (Ocn), type I collagen (Col1), runt-related transcription factor-2 (Runx2), and bone morphogenetic protein-2 (Bmp2), indicating their excellent osteogenic effect. As a result, 3D-printed MgHAp/GelMA-PDA@DOX hydrogels showed great potential in the treatment of bone tumor-related defects by effectively killing tumor cells and simultaneously promoting bone tissue regeneration.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141828049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}