Biofabrication最新文献

{"title":"Purified adipose tissue-derived extracellular vesicles facilitate adipose organoid vascularization through coordinating adipogenesis and angiogenesis.","authors":"Congxiao Zhu, Zonglin Huang, Hongru Zhou, Xuefeng Han, Lei Li, Ningbei Yin","doi":"10.1088/1758-5090/adb2e7","DOIUrl":"10.1088/1758-5090/adb2e7","url":null,"abstract":"<p><p>One of the major challenges in the way of better fabricating vascularized adipose organoids is the destructive effect of adipogenic differentiation on preformed vasculature, which probably stems from the discrepancy between the<i>in vivo</i>physiological microenvironment and the<i>in vitro</i>culture conditions. As an intrinsic component of adipose tissue (AT), adipose tissue-derived extracellular vesicles (AT-EVs) have demonstrated both adipogenic and angiogenic ability in recent studies. However, whether AT-EVs could be employed to coordinate the angiogenesis and adipogenesis in the vascularization of adipose organoids remains largely unexplored. Herein, we present an efficient method for isolating higher-purity AT-EV preparations from lipoaspirates, and verify the superiority of AT-EV preparations' angiogenic and adipogenic capabilities over those from unpurified lipoaspirates. Next, in the spheroid culture model, it was discovered that the addition of AT-EVs could effectively improve the aggregation through enhancing intercellular adhesion of monoculture spheroids composed of human umbilical vascular endothelial cells (HUVECs), and helped produce vascularized adipose organoids with proper lipolysis and glucose uptake ability in the coculture spheroids comprised of adipose-derived stem cells (ADSCs) and HUVECs. Subsequently, it was observed that AT-EVs could exert a retaining effect on the vasculature of prevascularized coculture spheroids cultured in an adipogenic environment, compared to the reduced vascular networks where AT-EVs were absent. Altogether, these results indicate that AT-EVs, by means of releasing bioactive molecules that emulate the<i>in vivo</i>microenvironment, can modify non-replicative<i>in vitro</i>microenvironments, coordinate<i>in vitro</i>adipogenesis and angiogenesis, and facilitate the fabrication of vascularized adipose organoids.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254350","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":"Current progress of<i>in vitro</i>vascular models on microfluidic chips.","authors":"Ran Wang, Hangyu Zhang, Shijun Li, Peishi Yan, Shuai Shao, Bo Liu, Na Li","doi":"10.1088/1758-5090/adb182","DOIUrl":"10.1088/1758-5090/adb182","url":null,"abstract":"<p><p>The vascular tissue, as an integral component of the human circulatory system, plays a crucial role in retaining normal physiological functions within the body. Pathologies associated with the vasculature, whether direct or indirect, also constitute significant public health concerns that afflict humanity, leading to the wide studies on vascular physiology and pathophysiology. Given the precious nature of human derived vascular tissue, substantial efforts have been dedicated to the construction of vascular models. Due to the high cost associated with animal experimentation and the inability to directly translate results to human, there is an increasing emphasis on the use of primary human cells for the development of<i>in vitro</i>vascular models. For instance, obtaining an ApoE^-/-mouse model for atherosclerosis research typically requires feeding a high-fat diet for over 10 weeks, whereas<i>in vitro</i>vascular models can usually be formed within 2 weeks. With advancements in microfluidic technology,<i>in vitro</i>vascular models capable of precisely emulating the hemodynamic environment within human vessels are becoming increasingly sophisticated. Microfluidic vascular models are primarily constructed through two approaches: (1) directly constructing the vascular models based on the three-layer structure of the vascular wall; (2) co-culture of endothelial cells and supporting cells within hydrogels. The former is effective to replicate vascular tissue structure mimicking vascular wall, while the latter has the capacity to establish microvascular networks. This review predominantly presents and discusses recent advancements in template design, construction methods, and potential applications of microfluidic vascular models based on polydimethylsiloxane (PDMS) soft lithography. Additionally, some refined methodologies addressing the limitations of conventional PDMS-based soft lithography techniques are also elaborated, which might hold profound importance in the field of vascular tissue engineering on microfluidic chips.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121990","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":"Enhanced osteogenic differentiation in hyaluronic acid methacrylate (HAMA) matrix: a comparative study of hPDC and hBMSC spheroids for bone tissue engineering.","authors":"Ane Albillos Sanchez, Filipa Castro Teixeira, Paula Casademunt, Ivo Beeren, Lorenzo Moroni, Carlos Mota","doi":"10.1088/1758-5090/adb2e6","DOIUrl":"10.1088/1758-5090/adb2e6","url":null,"abstract":"<p><p>Bone tissue engineering (BTE) seeks to overcome the limitations of traditional bone repair methods, such as autografts and allografts, which are often limited by availability, donor-site morbidity, immune rejection, and infection risks. Recent advancements have highlighted the potential of spheroids or microtissues as building blocks for BTE. This study aimed to investigate the osteogenic differentiation of spheroids formed from human periosteum-derived cells (hPDCs) and bone marrow-derived mesenchymal stromal cells (hBMSCs) in a hyaluronic acid methacrylate (HAMA) matrix, using encapsulation and extrusion bioprinting methods. Results showed significant morphological changes, high viability, and osteogenic differentiation of spheroids from hPDCs or hBMSCs in three-dimensional HAMA environments. Notably, hPDC spheroids demonstrated higher mineralization capabilities and superior hydrogel colonization than hBMSC spheroids. These findings reveal the potential of HAMA bioink containing hPDC spheroids to produce mineralized bone grafts using a bioprinting approach.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254217","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":"Bioinks for engineering gradient-based osteochondral and meniscal tissue substitutes: a review.","authors":"Mahdieh Heydarigoojani, Maryam Farokhi, Sara Simorgh","doi":"10.1088/1758-5090/adb0f4","DOIUrl":"10.1088/1758-5090/adb0f4","url":null,"abstract":"<p><p>Gradient tissues are anisotropic structure with gradual transition in structural and biological properties. The gradient in structural, mechanical and biochemical properties of osteochondral and meniscal tissues play a major role in defining tissue functions. Designing tissue substitutes that replicate these gradient properties is crucial to facilitate regeneration of tissue functions following injuries. Advanced manufacturing technologies such as 3D bioprinting hold great potentials for recreating gradient nature of tissues through using zone-specific bioinks and layer-by-layer deposition of spatially defined biomaterials, cell types and bioactive cues. This review highlighted the gradients in osteochondral and meniscal tissues in detail, elaborated on individual components of the bioink, and reviewed recent advancements in 3D gradient-based osteochondral and meniscal tissue substitutes. Finally, key challenges of the field and future perspectives for developing gradient-based tissue substitutes were discussed. The insights from these advances can broaden the possibilities for engineering gradient tissues.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073660","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":"Advancement of 3D biofabrication in repairing and regeneration of cartilage defects.","authors":"Zenghui Zheng, Dongmei Yu, Haoyu Wang, Hao Wu, Zhen Tang, Qi Wu, Pengfei Cao, Zhiyuan Chen, Hai Huang, Xiaokang Li, Chaozong Liu, Zheng Guo","doi":"10.1088/1758-5090/ada8e1","DOIUrl":"10.1088/1758-5090/ada8e1","url":null,"abstract":"<p><p>Three-dimensional (3D) bioprinting, an additive manufacturing technology, fabricates biomimetic tissues that possess natural structure and function. It involves precise deposition of bioinks, including cells, and bioactive factors, on basis of computer-aided 3D models. Articular cartilage injuries, a common orthopedic issue. Current repair methods, for instance microfracture procedure (MF), autologous chondrocyte implantation (ACI), and osteochondral autologous transfer surgery have been applied in clinical practice. However, each procedure has inherent limitation. For instance, MF surgery associates with increased subchondral cyst formation and brittle subchondral bone. ACI procedure involves two surgeries, and associate with potential risks infection and delamination of the regenerated cartilage. In addition, chondrocyte implantation's efficacy depends on the patient's weight, joint pathology, gender-related histological changes of cartilage, and hormonal influences that affect treatment and prognosis. So far, it is a still a grand challenge for achieving a clinical satisfactory in repairing and regeneration of cartilage defects using conditional strategies. 3D biofabrication provide a potential to fabricate biomimetic articular cartilage construct that has shown promise in specific cartilage repair and regeneration of patients. This review reported the techniques of 3D bioprinting applied for cartilage repair, and analyzed their respective merits and demerits, and limitations in clinical application. A summary of commonly used bioinks has been provided, along with an outlook on the challenges and prospects faced by 3D bioprinting in the application of cartilage tissue repair. It provided an overall review of current development and promising application of 3D biofabrication technology in articular cartilage repair.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963690","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":"One-step bioprinting of endothelialized, self-supporting arterial and venous networks.","authors":"Betty Cai, David Kilian, Sadegh Ghorbani, Julien G Roth, Alexis J Seymour, Lucia G Brunel, Daniel Ramos Mejia, Ricardo J Rios, Isabella M Szabo, Sean Chryz Iranzo, Andy Perez, Rameshwar R Rao, Sungchul Shin, Sarah C Heilshorn","doi":"10.1088/1758-5090/adab26","DOIUrl":"10.1088/1758-5090/adab26","url":null,"abstract":"<p><p>Advances in biofabrication have enabled the generation of freeform perfusable networks mimicking vasculature. However, key challenges remain in the effective endothelialization of these complex, vascular-like networks, including cell uniformity, seeding efficiency, and the ability to pattern multiple cell types. To overcome these challenges, we present an integrated fabrication and endothelialization strategy to directly generate branched, endothelial cell-lined networks using a diffusion-based, embedded 3D bioprinting process. In this strategy, a gelatin microparticle sacrificial ink delivering both cells and crosslinkers is extruded into a crosslinkable gel precursor support bath. A self-supporting, perfusable structure is formed by diffusion-induced crosslinking, after which the sacrificial ink is melted to allow cell release and adhesion to the printed lumen. This approach produces a uniform cell lining throughout networks with complex branching geometries, which are challenging to uniformly and efficiently endothelialize using conventional perfusion-based approaches. Furthermore, the biofabrication process enables high cell viability (>90%) and the formation of a confluent endothelial layer providing vascular-mimetic barrier function and shear stress response. Leveraging this strategy, we demonstrate for the first time the patterning of multiple endothelial cell types, including arterial and venous cells, within a single arterial-venous-like network. Altogether, this strategy enables the fabrication of multi-cellular engineered vasculature with enhanced geometric complexity and phenotypic heterogeneity.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999557","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":"Recent trends in embedded 3D bioprinting of vascularized tissue constructs.","authors":"Won-Woo Cho, Wonbin Park, Dong-Woo Cho","doi":"10.1088/1758-5090/adafdd","DOIUrl":"10.1088/1758-5090/adafdd","url":null,"abstract":"<p><p>3D bioprinting technology offers significant advantages in the fabrication of tissue and organ structures by allowing precise layer-by-layer patterning of cells and various biomaterials. However, conventional bioinks exhibit poor mechanical properties, which limit their use in the fabrication of large-scale vascularized tissue constructs. To address these limitations, recent studies have focused on the development of rapidly crosslinkable bioinks through chemical modification. These enable rapid crosslinking within minutes, offering substantial advantages for engineering large-scale tissue constructs. Nevertheless, challenges remain in the production of constructs that fully incorporate the complex vascular networks inherent to native tissues. Recently, embedded bioprinting technique, which involves the direct writing of bioink into a support bath that provides physical support, has gained significant attention for enabling the freeform fabrication of 3D structures. This method has been extensively studied and offers the advantage of fabricating structures ranging from tissue constructs with simple vascular channels to complex structures containing multiscale vascular networks. This review presents an overview of the various materials utilized in embedded bioprinting and elucidates the rheological properties of these materials. Furthermore, it examines the current research trends in the biofabrication of vascularized tissue constructs using embedded bioprinting techniques, along with their associated limitations. The review concludes by proposing areas for future improvement, specifically addressing material and biofabrication approaches as well as bioprinting systems.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063494","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":"Digital light processing 3D bioprinting of biomimetic corneal stroma equivalent using gelatin methacryloyl and oxidized carboxymethylcellulose interpenetrating network hydrogel.","authors":"Rashik Chand, Gopinathan Janarthanan, Kamil Elkhoury, Sanjairaj Vijayavenkataraman","doi":"10.1088/1758-5090/adab27","DOIUrl":"10.1088/1758-5090/adab27","url":null,"abstract":"<p><p>Corneal blindness, a leading cause of visual impairment globally, has created a pressing need for alternatives to corneal transplantation due to the severe shortage of donor tissues. In this study, we present a novel interpenetrating network hydrogel composed of gelatin methacryloyl (GelMA) and oxidized carboxymethyl cellulose (OxiCMC) for bioprinting a biomimetic corneal stroma equivalent. We tested different combinations of GelMA and OxiCMC to optimize printability and subsequently evaluated these combinations using rheological studies for gelation and other physical, chemical, and biological properties. Using digital light processing (DLP) bioprinting, with tartrazine as a photoabsorber, we successfully biofabricated three-dimensional constructs with improved shape fidelity, high resolution, and excellent reproducibility. The bioprinted constructs mimic the native corneal stroma's curvature, with central and peripheral thicknesses of 478.9 ± 56.5<i>µ</i>m and 864.0 ± 79.3<i>µ</i>m, respectively. The dual crosslinking strategy, which combines Schiff base reaction and photocrosslinking, showed an improved compressive modulus (106.3 ± 7.7 kPa) that closely matched that of native tissues (115.3 ± 13.6 kPa), without relying on synthetic polymers, toxic crosslinkers, or nanoparticles. Importantly, the optical transparency of tartrazine-containing corneal constructs was comparable to the native cornea following phosphate-buffered saline washing. Morphological analyses using scanning electron microscopy confirmed the improved porosity, interconnected network, and structural integrity of the GelMA-OxiCMC hydrogel, facilitating better nutrient diffusion and cell viability.<i>In vitro</i>biological assays demonstrated high cell viability (>93%) and desirable proliferation of human corneal keratocytes within the biofabricated constructs. Our findings indicate that the GelMA-OxiCMC hydrogel system for DLP bioprinting presents a promising alternative for corneal tissue engineering, offering a potential solution to the donor cornea shortage and advancing regenerative medicine for corneal repair.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999546","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":"Collagen silver-doped hydroxyapatite scaffolds reinforced with 3D printed frameworks for infection prevention and enhanced repair of load-bearing bone defects.","authors":"Katelyn J Genoud, Joanna M Sadowska, Rachael N Power, Lara S Costard, Emily J Ryan, Austyn R Matherson, Arlyng G Gonzalez-Vazquez, Mark Lemoine, Kian Eichholz, Pierluca Pitacco, Gang Chen, Brenton Cavanagh, Orquidea Garcia, Ciara M Murphy, Caroline M Curtin, Daniel J Kelly, Fergal J O'Brien","doi":"10.1088/1758-5090/adaf59","DOIUrl":"10.1088/1758-5090/adaf59","url":null,"abstract":"<p><p>Osteomyelitis, a severe bone infection, is an extremely challenging complication in the repair of traumatic bone defects. Furthermore, the use of long-term high-dose antibiotics in standard treatment increases the risks of antibiotic resistance. Herein, an antibiotic-free, collagen silver-doped hydroxyapatite (coll-AgHA) scaffold reinforced with a 3D printed polycaprolactone (PCL) framework was developed with enhanced mechanical properties to be used in the repair of load-bearing defects with antimicrobial properties as a preventative measure against osteomyelitis. The AgHA particles were fabricated in varying Ag doses and loaded within freeze-dried collagen scaffolds at two concentrations. The optimised Ag dose (1.5 mol% Ag) and AgHA concentration (200 wt%) within the collagen scaffold demonstrated<i>in vitro</i>osteogenic and antibacterial properties against<i>S. aureus (S. aureus),</i>the main causative pathogen of osteomyelitis. The addition of the PCL framework to the coll-AgHA scaffolds significantly enhanced the compressive modulus from 4 to 12 MPa while maintaining high porosity as well as both pro-osteogenic and antibacterial properties. The reinforced coll-AgHA scaffolds were implanted<i>in vivo</i>and demonstrated enhanced bone repair, significantly greater vessel formation, and calcified tissue in a load-bearing critical sized defect in rats. Taken together, these results confirm the capacity of this novel biomaterial scaffold as a preventative measure against infection in bone repair for use in load-bearing defects, without the use of antibiotics.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057845","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":"Advances in biomaterials-based tissue engineering for regeneration of female reproductive tissues.","authors":"Yong Ho Kim, Hyung-Sik Kim, In-Sun Hong","doi":"10.1088/1758-5090/adae38","DOIUrl":"10.1088/1758-5090/adae38","url":null,"abstract":"<p><p>The anatomical components of the female reproductive system-comprising the ovaries, uterus, cervix, vagina, and fallopian tubes-interact intricately to provide the structural and hormonal support essential for reproduction. However, this system is susceptible to various detrimental factors, both congenital and acquired, that can impair fertility and adversely affect quality of life. Recent advances in bioengineering have led to the development of sophisticated three-dimensional models that mimic the complex architecture and functionality of reproductive organs. These models, incorporating diverse cell types and tissue layers, are crucial for understanding physiological processes within the reproductive tract. They offer insights into decidualization, ovulation, folliculogenesis, and the progression of reproductive cancers, thereby enhancing personalized medical treatments and addressing female infertility. This review highlights the pivotal role of tissue engineering in diagnosing and treating female infertility, emphasizing the importance of considering factors like biocompatibility, biomaterial selection, and mechanical properties in the design of bioengineered systems. The challenge of replicating the functionally specialized and structurally complex organs, such as the uterus and ovary, underscores the need for reliable techniques that improve morphological and functional restoration. Despite substantial progress, the goal of creating a fully artificial female reproductive system is still a challenge. Nonetheless, the recent fabrication of artificial ovaries, uteruses, cervixes, and vaginas marks significant advancements toward this aim. Looking forward, the challenges in bioengineering are expected to spur further innovations in both basic and applied sciences, potentially hastening the clinical adoption of these technologies.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036653","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}