Biofabrication最新文献

{"title":"Validation of the exosomal protein SERPINA11 as a potential atherosclerosis marker via bioprinted scaffold.","authors":"Kyung-Seob Kim, Seung-Cheol Choi, Ji-Min Noh, Myeong-Hwa Song, Seongmin Jun, Ji Eun Na, Im Joo Rhyu, Do-Sun Lim","doi":"10.1088/1758-5090/add8bf","DOIUrl":"https://doi.org/10.1088/1758-5090/add8bf","url":null,"abstract":"<p><p>Existing animal and human cell models have limitations in terms of heterogeneous differences or difficulties in sufficiently reproducing arterial structures and complex cell-cell interactions. The discovery of exosome-derived biomarkers using a 3D bioprinted atherosclerosis model provides a noninvasive and stable detection method and is expected to contribute to the development of early diagnosis and personalized treatment. To contribute to the discovery of exosome-derived biomarkers related to the early diagnosis and prognosis of cardiovascular diseases using a 3D bioprinted atherosclerosis model, we reproduced an arterial environment using 3D bioprinting composed of a biocompatible extracellular matrix (bioink) and various human cells in vitro. The 3D bioprintedatherosclerosis model composed of inflammatory macrophages, coronary artery smooth muscle cells, coronary artery endothelial cells, and collagen methacryloyl (ColMA) hydrogel was treated with LDL to induce atherosclerosis, and the atherosclerosis model was classified into Baseline (BL), Early Atherosclerosis (EA; Early Athero), and Late Atherosclerosis (LA; Late Athero) groups. The secreted exosomes were isolated according to the time period, and a characterization analysis was conducted to confirm the purity of the isolated exosomes. We evaluated the isolated exosomes qualitatively and quantitatively. Isolated exosomes were analyzed using proteomics and miRNA sequencing to verify whether the bioprinted atherosclerosis model induced atherosclerosis, and a novel early atherosclerosis biomarker, SERPINA11, was discovered. In conclusion, we verified that the bioprinted atherosclerosis model induced atherosclerosis and that the novel biomarker set of exosomal miRNAs (hsa-miR-143-5p and hsa-miR-6879-5p) expressed in early atherosclerosis and proteins (SERPINA11, AHSG, and F2) might be clinically useful in early diagnosis and prognosis.&#xD.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075785","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":"Bioprinted M2 macrophage-derived extracellular vesicle mimics attenuate foreign body reaction and enhance vascularized tissue regeneration.","authors":"Chao Zhang, Ze Fu, Qinghua Liu, Xu Guo, Zhao Li, Wei Song, Yi Kong, Jinpeng Du, Yanlin Su, Bingyang Yu, Yue Kong, Feng Tian, Xiaobing Fu, Xiaohui Du, Sha Huang","doi":"10.1088/1758-5090/add49f","DOIUrl":"https://doi.org/10.1088/1758-5090/add49f","url":null,"abstract":"<p><p>Foreign body reaction (FBR) and insufficient vascularization greatly hinder the integration of 3D-bioprinted tissue substitutes with host tissues. Previous studies have shown that these problems are exacerbated by the stiffness of the 3D-bioprinted constructions, which is highly associated with the abnormal polarization of macrophages. Therefore, we developed an engineering strategy using membrane extrusion to prepare macrophage-derived extracellular vesicle mimics (EVMs). The EVMs derived from M1 and M2 macrophages (M1-EVMs and M2-EVMs) were rich in functional proteins. In the 2D environment, M1-EVMs promoted the fibrotic phenotype of fibroblasts, vascularization, and the M1 polarization of macrophages. In contrast, M2-EVMs effectively avoided the fibrotic trend, showed stronger angiogenic capabilities, and prevented excessive M1 polarization, demonstrating their potential to inhibit FBR and promote neovascularization. After bioprinting the EVMs loaded by gelatin-alginate bioink, the basic physical properties of the bioink were not significantly affected, and the biological functions of EVMs remain stable, indicating their potential as bioink additives. In the subcutaneous implantation model, unlike the FBR-aggravating effects of M1-EVMs, 3D-bioprinted M2-EVMs successfully reduced the immune response, prevented fibrous capsule formation, and increased vascular density. When applied to skin wound treatment, 3D-bioprinted M2-EVMs not only inhibited inflammatory levels but also exhibited pleiotropic pro-regenerative effects, effectively promoting vascularization, re-epithelialization, and appendage regeneration. As an innovative additive for bioinks, M2-EVMs present a promising approach to enhance the survival of bioengineered tissues and can further serve as a targeted drug loading system, promoting the development of regenerative medicine and improving clinical outcomes.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":"17 3","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972633","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":"Ultra-tiny-scale technology for engineering human ear therapeutics.","authors":"Harshita Sharma, Woochan Kim, Sejong Oh, Dream Kim, Shinyull Lee, Sangbae Park, Jooseon Oh, Sunho Park, Jangho Kim","doi":"10.1088/1758-5090/add210","DOIUrl":"https://doi.org/10.1088/1758-5090/add210","url":null,"abstract":"<p><p>Ultra-tiny-scale technology representing engineered micro- and nano-scale materials has gained considerable attention for a wide range of applications, including hearing restoration. The advent of hearing loss and its recovery has been the topic of intense discussion since many decades. Although conventional treatments partially support hearing recovery, they present certain limitations such as subsequent immune response and donor site morbidity leading to even worsened sensory disturbances. Microscale- and nanoscale-based approaches such as tissue engineering, nanoparticle-assisted drug delivery systems, and micro/nanofabrication-aided auditory stimulations have been shown to play an efficient role in recovery from hearing disorders. In particular, the introduction of different biomaterials and biopolymers (natural and synthetic) with influential topographical cues and excellent biocompatibility has been found to conveniently bypass previous challenges posed by rigid human ear structures and provided a new path for improved and advanced hearing-recovery approaches. This review is focused on the development of micro/nanoengineering-based hearing recovery therapeutics and their significant impact on the future of hearing research. It discusses the physiological functions associated with the human ear and the mechanism underlying distinct hearing loss disorders as well as highlights various engineered ultra-tiny-scale-assisted strategies for developing advanced hearing therapeutics. Finally, we deliberate on commercialization aspect and future perspectives of implementing micro/nanotechnologies for hearing restoration platforms.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":"17 3","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961891","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":"Development of a bioreactor and volumetric bioprinting protocol to enable perfused culture of biofabricated human epithelial mammary ducts and endothelial constructs.","authors":"Maj-Britt Buchholz, Paulina Nunez Bernal, Nils Bessler, Camille Bonhomme, Riccardo Levato, Anne Rios","doi":"10.1088/1758-5090/add20f","DOIUrl":"https://doi.org/10.1088/1758-5090/add20f","url":null,"abstract":"<p><p>Tissue function depends on the 3D spatial organization of cells, extracellular matrix components, as well as dynamic nutrient gradients and mechanical forces. Advances in biofabrication technologies have enabled the creation of increasingly sophisticated tissue models, but achieving native-like tissue maturation post-fabrication remains a challenge. The development of bioreactors and microfluidic systems capable of introducing dynamic culture platforms and controlled mechanical and biochemical stimulation for biofabricated tissue analogues is therefore imperative to address this. In this technical note, we introduce a multi-step pipeline to fabricate, seed and perfuse geometrically complex hydrogel constructs with quality control protocols through the computational analysis of confocal multispectral 3D imaging data for each step of the process. Employing ultra-fast volumetric bioprinting, chips with tunable channel architectures were fabricated. Furthermore, an autoclavable and transparent perfusion bioreactor inspired by open-source designs was developed to enable controlled, long-term perfusion (up to 28 days) and real-time monitoring of cell behavior. As proof-of-concept, employing this pipeline, we fabricated a human mammary ductal model and an endothelialized vessel on-a-chip, demonstrating the compatibility of the platform with epithelial and endothelial cell lines, and investigated the effect of dynamic culture on tissue-specific cell organization. Dynamic perfusion underlined the influence of mechanical stimulation on cell organization and maturation. Various chip architectures, capable of recapitulating tissue-specific features (<i>i.e.</i>lobules) were printed, enabling the mono- and co-culture of human mammary epithelial and endothelial cells. Our pipeline, with the accompanying protocols and analysis scripts presented here, provide the potential to be applied for the dynamic culture of a wide range of tissues.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":"17 3","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953505","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":"Simulating big mechanically-active culture systems (BigMACS) using paired biomechanics-histology FEA modelling to derive mechanobiology design relationships.","authors":"Sabrina Schoenborn, Mingyang Yuan, Cody A Fell, Chuanhai Liu, David F Fletcher, Selene Priola, Hon Fai Chan, Mia Woodruff, Zhiyong Li, Yi-Chin Toh, Mark C Allenby","doi":"10.1088/1758-5090/adcd9f","DOIUrl":"https://doi.org/10.1088/1758-5090/adcd9f","url":null,"abstract":"<p><p>Big mechanically-active culture systems (BigMACS) are promising to stimulate, control, and pattern cell and tissue behaviours with less soluble factor requirements. However, it remains challenging to predict if and how distributed mechanical forces impact single-cell behaviours to pattern tissue. In this study, we introduce a tissue-scale finite element analysis framework able to correlate sub-cellular quantitative histology with centimetre-scale biomechanics. Our framework is relevant to diverse BigMACS, including media perfusion, tensile-stress, magnetic, and pneumatic tissue culture platforms. We apply our framework to understand how the design and operation of a multi-axial soft robotic bioreactor can spatially control mesenchymal stem cell (MSC) proliferation, orientation, differentiation to smooth muscle, and extracellular vascular matrix deposition. We find MSC proliferation and matrix deposition to positively correlate with mechanical stimulation but cannot be locally patterned by soft robot mechanical stimulation within a centimetre scale tissue. In contrast, local stress distribution was able to locally pattern MSC orientation and differentiation to smooth muscle phenotypes, where MSCs aligned perpendicular to principal stress direction and expressed increased α-SMA with increasing 3D Von Mises Stresses from 0 to 15 kPa. Altogether, our new biomechanical-histological simulation framework is a promising technique to derive the future mechanical design equations to control cell behaviours and engineer patterned tissue.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":"17 3","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960869","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":"Filamented light (FLight) biofabrication of mini-tendon models show tunable matrix confinement and nuclear morphology.","authors":"Hao Liu, Lynn Scherpe, Linnea B Hummer, Jess Gerrit Snedeker, Marcy Zenobi-Wong","doi":"10.1088/1758-5090/adce35","DOIUrl":"https://doi.org/10.1088/1758-5090/adce35","url":null,"abstract":"<p><p>One hallmark of healthy tendon tissue is the high confinement of tenocytes between tightly packed, highly aligned collagen fibers. During tendinopathy, this organization becomes dysregulated, leading to cells with round-shaped morphology and collagen fibers which exhibit crimping and misalignment. The elongated nuclei in healthy tendons are linked to matrix homeostasis through distinct mechanotransduction pathways, and it is believed that the loss of nuclear confinement could upregulate genes associated with abnormal matrix remodeling. Replicating the cell and nuclear morphology of healthy and diseased states of tendon, however, remains a significant challenge for engineered<i>in vitro</i>tendon models. Here we report on a high throughput biofabrication of mini-tendons that mimick the tendon core compartment based on the filamented light (FLight) approach. Each mini-tendon, with a length of 4 mm, was composed of parallel hydrogel microfilaments (2-5<i>µ</i>m diameter) and microchannels (2-10<i>µ</i>m diameter) that confined the cells. We generated four distinct matrices with varying stiffness (7-40 kPa) and microchannel dimensions. After 14 d of culture, 29% of tenocytes in the softest matrix with the largest microchannel diameter were aligned, exhibiting an average nuclear aspect ratio (nAR) of 2.1. In contrast, 84% of tenocytes in the stiffest matrix with the smallest microchannel diameter were highly aligned, with a mean nAR of 3.4. When tenocytes were cultured<i>on</i>the FLight hydrogels (2D) as opposed to within the hydrogels three-dimensional (3D), the mean nAR was less than 1.9, indicating that nuclear morphology is significantly more confined in 3D environments. By tuning the stiffness and microarchitecture of the FLight matrix, we demonstrated that mechanical confinement can be modulated to exert control over the extent of nuclear confinement. This high-throughput, tunable platform offers a promising approach for studying the mechanobiology of healthy and diseased tendons and for eventual testing of drug compounds against tendinopathy.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":"17 3","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974166","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":"Cardiomyocyte sheet stacking using fibrin enables high-speed construction of three-dimensional myocardial tissue and high transplantation efficiency.","authors":"Katsuhisa Sakaguchi, Kazuki Nakazono, Kodai Tahara, Yuto Hinata, Yusuke Tobe, Jun Homma, Hidekazu Sekine, Katsuhisa Matsuura, Kiyotaka Iwasaki, Satoshi Tsuneda, Tatsuya Shimizu","doi":"10.1088/1758-5090/adcb6e","DOIUrl":"https://doi.org/10.1088/1758-5090/adcb6e","url":null,"abstract":"<p><p>Despite the development of three-dimensional (3D) tissues that promises remarkable advances in myocardial therapies and pharmaceutical research, vascularization is required for the repair of damaged hearts using cardiac tissue engineering. In this study, we developed a method for rapid generation of a 3D cardiac tissue, with extremely high engraftment efficiency, by stacking cardiomyocyte sheets using fibrin as an adhesive. Cell sheets were created by peeling off confluent cultured cells from a culture dish grafted with a polymer that induced surface hydrophilicity in response to low temperatures. The high engraftment rate was attributed to the retention of the adhesive protein. The multistacked vascularized cell sheets prepared using fibrin, when transplanted into the subcutaneous tissue and at myocardial infarction site in rats, yielded a transplanted 3D myocardial tissue. Furthermore, multilayered cardiomyocyte sheets were transplanted twice at 1 week intervals to create a 3D myocardial tissue. Our data suggest that fibrin-based rapidly layered cell sheets can advance tissue-engineered transplantation therapy and should aid the development of next-generation tissue-engineered products in the fields of regenerative medicine and drug screening.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":"17 3","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975926","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":"Review of 3D-printed bioceramic/biopolymer composites for bone regeneration: fabrication methods, technologies and functionalized applications.","authors":"Yumeng Tang, Yi Zhang, Li Zou, Chengli Sun, Weizhe Tang, Youce Zou, Aiwu Zhou, Weili Fu, Fuyou Wang, Kang Li, Qiang Zhang, Xiaosheng Zhang","doi":"10.1088/1758-5090/adcbd7","DOIUrl":"https://doi.org/10.1088/1758-5090/adcbd7","url":null,"abstract":"<p><p>Biomaterials for orthopedic applications must have biocompatibility, bioactivity, and optimal mechanical performance. A suitable biomaterial formulation is critical for creating desired devices. Bioceramics with biopolymer composites and biomimetics with components similar to that of bone tissue, have been recognized as an area of research for orthopedic applications. The combination of bioceramics with biopolymers has the advantage of satisfying the need for robust mechanical support and extracellular matrices at the same time. Three-dimensional (3D) printing is a powerful method for restoring large bone defects and skeletal abnormalities owing to the favorable merits of preparing large, porous, patient-specific, and other intricate architectures. Bioceramic/biopolymer composites produced using 3D printing technology have several advantages, including desirable optimal architecture, enhanced tissue mimicry, and improved biological and physical properties. This review describes various 3D printing bioceramic/biopolymer composites for orthopedic applications. We hope that these technologies will inspire the future design and fabrication of 3D printing bioceramic/biopolymer composites for clinical and commercial applications.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":"17 3","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972715","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":"Biofabrication of small-diameter vascular graft with acellular human amniotic membrane: a proof-of-concept study in pig.","authors":"O Aung, Peter J Rossi, Yingnan Zhai, Kenneth P Allen, Mitchell R Dyer, Jackie Chang, Xiaolong Wang, Chase Caswell, Austin Stellpflug, Yiliang Chen, Brandon J Tefft, Linxia Gu, Rongxue Wu, Bo Wang","doi":"10.1088/1758-5090/adcb6d","DOIUrl":"https://doi.org/10.1088/1758-5090/adcb6d","url":null,"abstract":"<p><p>Expanded polytetrafluoroethylene (ePTFE) grafts are Food and Drug Administration approved and effective for large vessel surgeries but face challenges in smaller vessels (Inner Diameter, ID ⩽ 6 mm) due to reduced blood flow and higher risks of thrombosis, stenosis, and infection. This study developed a vascular graft with an ID of 6 mm from decellularized human amniotic membrane (DAM graft) and compared its performance to ePTFE grafts in a porcine carotid artery model for one month. DAM grafts retained key extracellular matrix structures and mechanical properties post-decellularization, with customizable layers and stiffness to meet specific clinical needs. DAM grafts demonstrated successful carotid artery replacement, showing good surgical feasibility, patency, and post-operative recovery in all animals. In contrast to ePTFE grafts, which exhibited significant neointimal hyperplasia (NIH), poor endothelialization, and inflammation, DAM grafts displayed organized endothelial coverage, smooth muscle alignment, and reduced inflammation, minimizing NIH, thrombosis, and graft failure. These findings position DAM grafts as a promising alternative to synthetic grafts, especially for small-diameter applications. Future research should focus on improving endothelialization, exploring molecular mechanisms, and assessing long-term outcomes to further optimize DAM grafts for clinical use.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":"17 3","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960745","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":"Injectable microgel and micro-granular hydrogels for bone tissue engineering.","authors":"Melika Mansouri Moghaddam, Elaheh Jooybar, Rana Imani","doi":"10.1088/1758-5090/adcc58","DOIUrl":"https://doi.org/10.1088/1758-5090/adcc58","url":null,"abstract":"<p><p>Injectable microgels, made from both natural and synthetic materials, are promising platforms for the encapsulation of cells or bioactive agents, such as drugs and growth factors, for delivery to injury sites. They can also serve as effective micro-scaffolds in bone tissue engineering (BTE), offering a supportive environment for cell proliferation or differentiation into osteoblasts. Microgels can be injected in the injury sites individually or in the form of aggregated/jammed ones named micro-granular hydrogels. This review focuses on common materials and fabrication techniques for preparing injectable microgels, as well as their characteristics and applications in BTE. These applications include their use as cell carriers, delivery systems for bioactive molecules, micro-granular hydrogels, bio-inks for bioprinting, three-dimensional microarrays, and the formation of microtissues. Furthermore, we discuss the current and potential future applications of microgels in bone tissue regeneration.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":"17 3","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967602","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}