{"title":"Rosalind Franklin Society Proudly Announces the 2023 Award Recipient for Tissue Engineering Part C.","authors":"Jenneke Klein-Nulend","doi":"10.1089/ten.tec.2024.33445.rfs2023","DOIUrl":"https://doi.org/10.1089/ten.tec.2024.33445.rfs2023","url":null,"abstract":"","PeriodicalId":23154,"journal":{"name":"Tissue engineering. Part C, Methods","volume":"1 1","pages":"365"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nickolas G Diodati, Zadia E Dupee, Felipe T Lima, Jack Famiglietti, Ryan A Smolchek, Ganlin Qu, Yana Goddard, Duy T Nguyen, W Gregory Sawyer, Edward A Phelps, Borna Mehrad, Matthew A Schaller
{"title":"3D Culture Analysis of Cancer Cell Adherence to <i>Ex Vivo</i> Lung Microexplants.","authors":"Nickolas G Diodati, Zadia E Dupee, Felipe T Lima, Jack Famiglietti, Ryan A Smolchek, Ganlin Qu, Yana Goddard, Duy T Nguyen, W Gregory Sawyer, Edward A Phelps, Borna Mehrad, Matthew A Schaller","doi":"10.1089/ten.TEC.2024.0146","DOIUrl":"10.1089/ten.TEC.2024.0146","url":null,"abstract":"<p><p><i>Ex vivo</i> 3D culture of human tissue explants addresses many limitations of traditional monolayer cell culture techniques, namely the lack of cellular heterogeneity and absence of 3D intercellular spatial relationships, but presents challenges with regard to repeatability owing to the difficulty of acquiring multiple tissue samples from the same donor. In this study, we used a cryopreserved bank of human lung microexplants, ∼1 mm<sup>3</sup> fragments of peripheral lung from donors undergoing lung resection surgery, and a liquid-like solid 3D culture matrix to describe a method for the analysis of non-small-cell lung cancer adhesion to human lung tissue. H226 (squamous cell carcinoma), H441 (lung adenocarcinoma), and H460 (large cell carcinoma) cell lines were cocultured with lung microexplants. Confocal fluorescence microscopy was used to visualize the adherence of each cell line to lung microexplants. Adherent cancer cells were quantified following filtration of nonadherent cells, digestion of cultured microexplants, and flow cytometry. This method was used to evaluate the role of integrins in cancer cell adherence. A statistically significant decrease in the adherence of H460 cells to lung microexplants was observed when anti-integrins were administered to H460 cells before coculture with lung microexplants.</p>","PeriodicalId":23154,"journal":{"name":"Tissue engineering. Part C, Methods","volume":" ","pages":"343-352"},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Erfan Jabari, Robert H Choe, Blake Kuzemchak, Alejandro Venable-Croft, Ji Young Choi, Shannon McLoughlin, Jonathan D Packer, John P Fisher
{"title":"Strategies for the Codelivery of Osteoclasts and Mesenchymal Stem Cells in 3D-Printable Osteochondral Scaffolds.","authors":"Erfan Jabari, Robert H Choe, Blake Kuzemchak, Alejandro Venable-Croft, Ji Young Choi, Shannon McLoughlin, Jonathan D Packer, John P Fisher","doi":"10.1089/ten.TEC.2024.0162","DOIUrl":"10.1089/ten.TEC.2024.0162","url":null,"abstract":"<p><p>Osteochondral defects, characterized by structural compromises to articular cartilage and subchondral bone, can cause pain and lead to progressive cartilage damage and eventual osteoarthritis. Unfortunately, repairing these defects remains difficult because of the poor regenerative properties of cartilage and complex mechanical demands of the joint. As such, the field of tissue engineering aims to develop multiphasic implants that replace pathological cartilage and bone tissue and restore mechanical functionality to the joint. Recent bone physiology investigations have demonstrated that osteoclast (OC) lineage cells are inextricably involved in osteoblastic bone formation through an extensive network of anabolic signaling pathways, and so the codelivery OC and osteoblast (OB) lineage cells within scaffolds is being actively explored for bone tissue engineering purposes. However, it remains unclear how these cells can be incorporated into the design of multiphasic osteochondral scaffolds to potentially enhance subchondral bone formation and subsequent implant osseointegration. To explore this question, we examined direct surface seeding and hydrogel encapsulation as potential scaffold cellularization strategies. First, we examined how OC precursor cells and peripheral blood monocytes (PBMCs) influence early-stage bone matrix development and osteogenesis in 2D coculture. Then, we evaluated the osteogenic potential of mesenchymal stem cells (MSCs) and PBMCs cocultures encapsulated within a gelatin methacrylate (GelMA) hydrogel system. Our findings demonstrate that coculturing PBMCs with MSCs in 2D cultures significantly enhanced cell proliferation, early bone matrix deposition, and the formation of cell clusters by Day 28. However, we observed no significant difference in type I collagen deposition between GelMA hydrogel scaffolds cultured in basal and OC conditions during the same period. In addition, we found that the GelMA hydrogel system with MSC/PBMC cocultures in OC conditions exhibited decreased osteogenic activity by Day 28. Collectively, our findings support the osteogenic potential of OC-lineage cells in 2D culture conditions, and the potential benefits of surface-seeding for the codelivery of OC-lineage cells and MSCs in osteo-scaffolds for enhanced osteochondral regeneration and broader bone tissue engineering purposes.</p>","PeriodicalId":23154,"journal":{"name":"Tissue engineering. Part C, Methods","volume":" ","pages":"323-334"},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rui Wang, Zejian Jin, Jianfeng Gao, Yan Ma, Qianqian Han
{"title":"Effectiveness and Biocompatibility Evaluation of a Novel Absorbable Bone Wax Used in Bone Tissue.","authors":"Rui Wang, Zejian Jin, Jianfeng Gao, Yan Ma, Qianqian Han","doi":"10.1089/ten.TEC.2024.0144","DOIUrl":"10.1089/ten.TEC.2024.0144","url":null,"abstract":"<p><p>This study aims to determine the hemostatic effectivity and biocompatibility of a novel absorbable bone wax in comparison with a commercially available product. Eighteen small fat-tail sheep were used to simulate clinical surface bleeding of sternal injury. Hemostasis effectiveness, the degree of bone healing, micro-computed tomography, and histopathology were evaluated over a period after the application of the material to the surgically created wound. The absorbable bone wax used in the study stopped bleeding immediately and did not affect bone healing. The histopathological results also showed that there were no complications associated with the new material. The results showed that the new absorbable bone wax used in this study was effective and biocompatible.</p>","PeriodicalId":23154,"journal":{"name":"Tissue engineering. Part C, Methods","volume":" ","pages":"353-363"},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ziyu Wang, Hugh Paterson, Lisa Partel, Innes Wise, Matthew Adams, David Cistulli, Dominic Ng, Raffi Qasabian, John O'Sullivan, Sean Lal, Anthony S Weiss, Paul Bannon, Robert D Hume
{"title":"Preventing Sheep Carotid Artery Spasm for Vascular Graft Surgery and Computed Tomography Angiography.","authors":"Ziyu Wang, Hugh Paterson, Lisa Partel, Innes Wise, Matthew Adams, David Cistulli, Dominic Ng, Raffi Qasabian, John O'Sullivan, Sean Lal, Anthony S Weiss, Paul Bannon, Robert D Hume","doi":"10.1089/ten.TEC.2024.0113","DOIUrl":"10.1089/ten.TEC.2024.0113","url":null,"abstract":"<p><p>The development of small-diameter vascular grafts requires testing in large animal models before advancing to clinical trials. Vascular graft interposition implantation in sheep carotid arteries (CAs) is the most widely used model, but ovine CAs are prone to severe spasm following surgical manipulation, potentially impairing graft performance assessment. There is paucity in the literature on reducing sheep CA spasm using effective vasodilator therapeutic protocols. In this study, four healthy Merino cross White Suffolk wethers (1-2 years, 52.1 ± 0.8 kg) underwent CT angiography and CA graft surgery. CT angiography using iodinated contrast agent was performed with innominate artery access through the CA or ascending aortic arch access through the femoral artery. Sheep then underwent right CA sham surgery or left CA vascular graft implantation. A variety of vasodilators, including papaverine, sodium nitroprusside, verapamil, and their combination, were tested for preventing or treating CA spasms intraoperatively. Blood flow was reassessed immediately after CA surgery using CT angiography. The results showed that innominate artery access through the CA for CT angiography in sheep induced presurgical CA spasm with reduced arterial flow. Conversely, ascending aortic arch access through the femoral artery for CT angiography did not cause CA spasm and maintained arterial flow. During CA graft surgery, surgical trauma induced CA spasm, which was prevented by localized intra-arterial administration of vasodilators papaverine hydrochloride and verapamil before significant surgical manipulation.</p>","PeriodicalId":23154,"journal":{"name":"Tissue engineering. Part C, Methods","volume":" ","pages":"335-342"},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexis Franco, Bo Van Durme, Sandra Van Vlierberghe, Christine Dupont-Gillain
{"title":"Misleading Pore Size Measurements in Gelatin and Alginate Hydrogels Revealed by Confocal Microscopy.","authors":"Alexis Franco, Bo Van Durme, Sandra Van Vlierberghe, Christine Dupont-Gillain","doi":"10.1089/ten.TEC.2024.0117","DOIUrl":"10.1089/ten.TEC.2024.0117","url":null,"abstract":"<p><p>It is a well-documented phenomenon that the porous structure of hydrogels observed with vacuum-based imaging techniques is generated during the freezing and drying process employed prior to observation. Nevertheless, vacuum-based techniques, such as scanning electron microscopy (SEM), are still being commonly used to measure pore sizes in hydrogels, which is often not representative of the actual pore size in hydrated conditions. The frequent underestimation of the impact of freezing and drying on hydrogel structures could stem from a lack of cross-fertilization between materials science and biomedical or food science communities, or from the simplicity and visually appealing nature of SEM imaging, which may lead to an overemphasis on its use. Our study provides a straightforward and impactful way of pinpointing this phenomenon exploiting two hydrogels ubiquitously applied in tissue engineering, including gelatin methacryloyl and alginate as proof-of-concept hydrogels. By comparing images of the samples in the native hydrated state, followed by freezing, freeze-drying, and rehydration using SEM and confocal microscopy, we highlight discrepancies between hydrogel pore sizes in the hydrated versus the dry state. To conclude, our study offers recommendations for researchers seeking insight in hydrogel properties and emphasizes key factors that require careful control when using SEM as a characterization tool.</p>","PeriodicalId":23154,"journal":{"name":"Tissue engineering. Part C, Methods","volume":" ","pages":"307-313"},"PeriodicalIF":2.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Auricular Chondrocytes as a Cell Source for Scaffold-Free Elastic Cartilage Tissue Engineering.","authors":"Nicole Gonzales, Carissa Garrity, Iris Rivas, Heather McEligot, Natalia Vapniarsky","doi":"10.1089/ten.TEC.2024.0106","DOIUrl":"10.1089/ten.TEC.2024.0106","url":null,"abstract":"<p><p>Current tissue engineering (TE) methods utilize chondrocytes primarily from costal or articular sources. Despite the robust mechanical properties of neocartilages sourced from these cells, the lack of elasticity and invasiveness of cell collection from these sources negatively impact clinical translation. These limitations invited the exploration of naturally elastic auricular cartilage as an alternative cell source. This study aimed to determine if auricular chondrocytes (AuCs) can be used for TE scaffold-free neocartilage constructs and assess their biomechanical properties. Neocartilages were successfully generated from a small quantity of primary neonatal AuCs of three minipig donors (<i>n</i> = 3). Neocartilage constructs had instantaneous moduli of 200.5 kPa ± 43.34 and 471.9 ± 92.8 kPa at 10% and 20% strain, respectively. TE constructs' relaxation moduli (Er) were 36.99 ± 6.47 kPa Er and 110.3 ± 16.99 kPa at 10% and 20% strain, respectively. The Young's modulus was 2.0 MPa ± 0.63, and the ultimate tensile strength was 0.619 ± 0.177 MPa. AuC-derived neocartilages contained 0.144 ± 0.011 µg collagen, 0.185 µg ± 0.002 glycosaminoglycans per µg dry weight, and 1.7e-3 µg elastin per µg dry weight. In conclusion, this study shows that AuCs can be used as a reliable and easily accessible cell source for TE of biomimetic and mechanically robust elastic neocartilage implants.</p>","PeriodicalId":23154,"journal":{"name":"Tissue engineering. Part C, Methods","volume":" ","pages":"314-322"},"PeriodicalIF":2.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carolyn A Nietupski, Andreja Moset Zupan, Stacey C Schutte
{"title":"Impact of Cyclic Strain on Elastin Synthesis in a 3D Human Myometrial Culture Model.","authors":"Carolyn A Nietupski, Andreja Moset Zupan, Stacey C Schutte","doi":"10.1089/ten.TEC.2024.0038","DOIUrl":"10.1089/ten.TEC.2024.0038","url":null,"abstract":"<p><p>The synthesis and assembly of mature, organized elastic fibers remains a limitation to the clinical use of many engineered tissue replacements. There is a critical need for a more in-depth understanding of elastogenesis regulation for the advancement of methods to induce and guide production of elastic matrix structures in engineered tissues that meet the structural and functional requirements of native tissue. The dramatic increase in elastic fibers through normal pregnancy has led us to explore the potential role of mechanical stretch in combination with pregnancy levels of the steroid hormones 17β-estradiol and progesterone on elastic fiber production by human uterine myometrial smooth muscle cells in a three-dimensional (3D) culture model. Opposed to a single strain regimen, we sought to better understand how the amplitude and frequency parameters of cyclic strain influence elastic fiber production in these myometrial tissue constructs (MTC). Mechanical stretch was applied to MTC at a range of strain amplitudes (5%, 10%, and 15% at 0.5 Hz frequency) and frequencies (0.1 Hz, 0.5 Hz, 1 Hz, and constant 0 Hz at 10% amplitude), with and without pregnancy-level hormones, for 6 days. MTC were assessed for cell proliferation, matrix elastin protein content, and expression of the main elastic fiber genes, tropoelastin (ELN) and fibrillin-1 (FBN1). Significant increases in elastin protein and ELN and FBN1 mRNA were produced from samples subjected to a 0.5 Hz, 10% strain regimen, as well as samples stretched at higher amplitude (15%, 0.5 Hz) and higher frequency (1 Hz, 10%); however, no significant effects because of third-trimester mimetic hormone treatment were determined. These results establish that a minimum level of strain is required to stimulate the synthesis of elastic fiber components in our culture model and show this response can be similarly enhanced by increasing either the amplitude or frequency parameter of applied strain. Further, our results demonstrate strain alone is sufficient to stimulate elastic fiber production and suggest hormones may not be a significant factor in regulating elastin synthesis. This 3D culture model will provide a useful tool to further investigate mechanisms underlying pregnancy-induced <i>de novo</i> elastic fiber synthesis and assembly by uterine smooth muscle cells.</p>","PeriodicalId":23154,"journal":{"name":"Tissue engineering. Part C, Methods","volume":" ","pages":"279-288"},"PeriodicalIF":2.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ying Betty Li, Marina Rukhlova, Dongling Zhang, Jordan Nhan, Caroline Sodja, Erin Bedford, Jean-Philippe St-Pierre, Anna Jezierski
{"title":"Single-Step 3D Bioprinting of Alginate-Collagen Type I Hydrogel Fiber Rings to Promote Angiogenic Network Formation.","authors":"Ying Betty Li, Marina Rukhlova, Dongling Zhang, Jordan Nhan, Caroline Sodja, Erin Bedford, Jean-Philippe St-Pierre, Anna Jezierski","doi":"10.1089/ten.TEC.2024.0083","DOIUrl":"10.1089/ten.TEC.2024.0083","url":null,"abstract":"<p><p>In the advent of tissue engineering and regenerative medicine, the demand for innovative approaches to biofabricate complex vascular structures is increasing. We describe a single-step 3D bioprinting method leveraging Aspect Biosystems RX1 technology, which integrates the crosslinking step at a flow-focusing junction, to biofabricate immortalized adult rat brain endothelial cell (SV-ARBEC)-encapsulated alginate-collagen type I hydrogel rings. This single-step biofabrication process involves the strategic layer-by-layer assembly of hydrogel rings, encapsulating SV-ARBECs in a spatially controlled manner while optimizing access to media and nutrients. The spatial arrangement of the SV-ARBECs within the rings promotes spontaneous angiogenic network formation and the constrained deposition of cells within the hydrogel matrix facilitates tissue-like organized vascular-like network development. This approach provides a platform that can be adapted to many different endothelial cell types and leveraged to better understand the mechanisms driving angiogenesis and vascular-network formation in 3D bioprinted constructs supporting the development of more complex tissue and disease models for advancing drug discovery, tissue engineering, and regenerative medicine applications.</p>","PeriodicalId":23154,"journal":{"name":"Tissue engineering. Part C, Methods","volume":" ","pages":"289-306"},"PeriodicalIF":2.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of Physicochemical Surface Properties of Silicon-Substituted Hydroxyapatite on Angiogenesis.","authors":"Else Ellermann, Ruth E Cameron, Serena M Best","doi":"10.1089/ten.TEC.2024.0086","DOIUrl":"10.1089/ten.TEC.2024.0086","url":null,"abstract":"<p><p>Synthetic hydroxyapatite (HA) is a widely studied bioceramic for bone tissue engineering (BTE) due to its similarity to the mineral component of bone. As bone mineral contains various ionic substitutions that play a crucial role in bone metabolism, the bioactivity of HA can be improved by adding small amounts of physiologically relevant ions into its crystal structure, with silicate-substituted HA (Si-HA) showing particularly promising results. Nevertheless, it remains unclear how distinct material characteristics influence the bioactivity due to the intertwined nature of surface properties. A coculture methodology was optimized and applied for <i>in vitro</i> quantification of the biological response. Initially, HA and Si-HA samples were produced and characterized. To compare the bioactivity of the samples, a method was developed to measure interactions in an increasingly complex environment, first including fibronectin (FN) adsorption and subsequently cell adhesion in mono and coculture using primary human osteoblasts (hOBs) and human dermal microvascular endothelial cells (HDMECs), with and without FN precoating. An experimental set-up was designed to assess to what extent different surface features of the samples contribute to the induced biological response. An 8-nm gold sputter coating was applied to eradicate the electrochemical differences and polishing and abrading was used to reduce the differences in surface topographies. Overall, 1.25 wt% Si-HA exhibited most nanoscale variations in surface potential. In terms of bioactivity, 1.25 wt% Si-HA samples induced the highest osteoblast attachment and vessel formation. Additionally, <i>in vitro</i> vessel formation was established on Si-HA surfaces using a hOB:HDMEC cell ratio of 70:30 and a methodology was established that enabled the assessment of the relative effect of topographical and electrochemical features induced by silicon substitution in the HA lattice on their bioactivity. It was found that the difference in the amount of protein attached to HA and 1.25 wt% Si-HA after 2 h was affected by topographical differences. Conversely, electrochemical differences induced different vessel-like structure formation in coculture with a FN precoating. Without an FN precoating, both topographical and electrochemical differences dictated the differences in angiogenic response. Overall, 1.25 wt% Si-HA surface features appear to induce the most favorable protein adsorption and cell adhesion in mono and coculture with and without FN precoating.</p>","PeriodicalId":23154,"journal":{"name":"Tissue engineering. Part C, Methods","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}