Panagiota Kakni, Barry Jutten, Daniel Teixeira Oliveira Carvalho, John Penders, Roman Truckenmüller, Pamela Habibovic, Stefan Giselbrecht
{"title":"Hypoxia-tolerant apical-out intestinal organoids to model host-microbiome interactions.","authors":"Panagiota Kakni, Barry Jutten, Daniel Teixeira Oliveira Carvalho, John Penders, Roman Truckenmüller, Pamela Habibovic, Stefan Giselbrecht","doi":"10.1177/20417314221149208","DOIUrl":"https://doi.org/10.1177/20417314221149208","url":null,"abstract":"<p><p>Microbiome is an integral part of the gut and is essential for its proper function. Imbalances of the microbiota can be devastating and have been linked with several gastrointestinal conditions. Current gastrointestinal models do not fully reflect the in vivo situation. Thus, it is important to establish more advanced in vitro models to study host-microbiome/pathogen interactions. Here, we developed for the first time an apical-out human small intestinal organoid model in hypoxia, where the apical surface is directly accessible and exposed to a hypoxic environment. These organoids mimic the intestinal cell composition, structure and functions and provide easy access to the apical surface. Co-cultures with the anaerobic strains <i>Lactobacillus casei</i> and <i>Bifidobacterium longum</i> showed successful colonization and probiotic benefits on the organoids. These novel hypoxia-tolerant apical-out small intestinal organoids will pave the way for unraveling unknown mechanisms related to host-microbiome interactions and serve as a tool to develop microbiome-related probiotics and therapeutics.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/85/d4/10.1177_20417314221149208.PMC9869231.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10677635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Soraya Williams, Aveen R Jalal, Mark P Lewis, Owen G Davies
{"title":"A survey to evaluate parameters governing the selection and application of extracellular vesicle isolation methods.","authors":"Soraya Williams, Aveen R Jalal, Mark P Lewis, Owen G Davies","doi":"10.1177/20417314231155114","DOIUrl":"https://doi.org/10.1177/20417314231155114","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) continue to gain interest across the scientific community for diagnostic and therapeutic applications. As EV applications diversify, it is essential that researchers are aware of challenges, in particular the compatibility of EV isolation methods with downstream applications and their clinical translation. We report outcomes of the first cross-comparison study looking to determine parameters (EV source, starting volume, operator experience, application and implementation parameters such as cost and scalability) governing the selection of popular EV isolation methods across disciplines. Our findings highlighted an increased clinical focus, with 36% of respondents applying EVs in therapeutics and diagnostics. Data indicated preferential selection of ultracentrifugation for therapeutic applications, precipitation reagents in clinical settings and size exclusion chromatography for diagnostic applications utilising biofluids. Method selection was influenced by operator experience, with increased method diversity when EV research was not the respondents primary focus. Application and implementation criteria were indicated to be major influencers in method selection, with UC and SEC chosen for their abilities to process large and small volumes, respectively. Overall, we identified parameters influencing method selection across the breadth of EV science, providing a valuable overview of practical considerations for the effective translation of research outcomes.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9996742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9104715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiah Shin Chin, Ulla Milbreta, David L Becker, Sing Yian Chew
{"title":"Targeting connexin 43 expression via scaffold mediated delivery of antisense oligodeoxynucleotide preserves neurons, enhances axonal extension, reduces astrocyte and microglial activation after spinal cord injury.","authors":"Jiah Shin Chin, Ulla Milbreta, David L Becker, Sing Yian Chew","doi":"10.1177/20417314221145789","DOIUrl":"https://doi.org/10.1177/20417314221145789","url":null,"abstract":"<p><p>Injury to the central nervous system (CNS) provokes an inflammatory reaction and secondary damage that result in further tissue damage and destruction of neurons away from the injury site. Upon injury, expression of connexin 43 (Cx43), a gap junction protein, upregulates and is responsible for the spread and amplification of cell death signals through these gap junctions. In this study, we hypothesise that the downregulation of Cx43 by scaffold-mediated controlled delivery of antisense oligodeoxynucleotide (asODN), would minimise secondary injuries and cell death, and thereby support tissue regeneration after nerve injuries. Specifically, using spinal cord injury (SCI) as a proof-of-principle, we utilised a fibre-hydrogel scaffold for sustained delivery of Cx43asODN, while providing synergistic topographical cues to guide axonal ingrowth. Correspondingly, scaffolds loaded with Cx43asODN, in the presence of NT-3, suppressed Cx43 up-regulation after complete transection SCI in rats. These scaffolds facilitated the sustained release of Cx43asODN for up to 25 days. Importantly, asODN treatment preserved neurons around the injury site, promoted axonal extension, decreased glial scarring, and reduced microglial activation after SCI. Our results suggest that implantation of such scaffold-mediated asODN delivery platform could serve as an effective alternative SCI therapeutic approach.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6e/0c/10.1177_20417314221145789.PMC9926388.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10748981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Modified black phosphorus quantum dots promotes spinal cord injury repair by targeting the AKT signaling pathway.","authors":"Dong-Mei Xie, Chuanwei Sun, Qingqiang Tu, Suyi Li, Yu Zhang, Xifan Mei, Yuanlong Li","doi":"10.1177/20417314231180033","DOIUrl":"https://doi.org/10.1177/20417314231180033","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a serious refractory disease of the central nervous system (CNS), which mostly caused by high-energy trauma. Existing interventions such as hormone shock and surgery are insufficient options, which relate to the secondary inflammation and neuronal dysfunction. Hydrogel with neuron-protective behaviors attracts tremendous attention, and black phosphorus quantum dots (BPQDs) encapsulating with Epigallocatechin-3-gallate (EGCG) hydrogels (E@BP) is designed for inflammatory modulation and SCI treatment in this study. E@BP displays good stability, biocompatibility and safety profiles. E@BP incubation alleviates lipopolysaccharide (LPS)-induced inflammation of primary neurons and enhances neuronal regeneration in vitro. Furthermore, E@BP reconstructs structural versus functional integrity of spinal cord tracts, which promotes recovery of motor neuron function in SCI rats after transplantation. Importantly, E@BP restarts the cell cycle and induces nerve regeneration. Moreover, E@BP diminishes local inflammation of SCI tissues, characterized by reducing accumulation of astrocyte, microglia, macrophages, and oligodendrocytes. Indeed, a common underlying mechanism of E@BP regulating neural regenerative and inflammatory responses is to promote the phosphorylation of key proteins related to AKT signaling pathway. Together, E@BP probably repairs SCI by reducing inflammation and promoting neuronal regeneration via the AKT signaling pathway.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d5/62/10.1177_20417314231180033.PMC10272649.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10291236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Raúl Sanz-Horta, Ana Matesanz, Alberto Gallardo, Helmut Reinecke, José Luis Jorcano, Pablo Acedo, Diego Velasco, Carlos Elvira
{"title":"Technological advances in fibrin for tissue engineering.","authors":"Raúl Sanz-Horta, Ana Matesanz, Alberto Gallardo, Helmut Reinecke, José Luis Jorcano, Pablo Acedo, Diego Velasco, Carlos Elvira","doi":"10.1177/20417314231190288","DOIUrl":"https://doi.org/10.1177/20417314231190288","url":null,"abstract":"<p><p>Fibrin is a promising natural polymer that is widely used for diverse applications, such as hemostatic glue, carrier for drug and cell delivery, and matrix for tissue engineering. Despite the significant advances in the use of fibrin for bioengineering and biomedical applications, some of its characteristics must be improved for suitability for general use. For example, fibrin hydrogels tend to shrink and degrade quickly after polymerization, particularly when they contain embedded cells. In addition, their poor mechanical properties and batch-to-batch variability affect their handling, long-term stability, standardization, and reliability. One of the most widely used approaches to improve their properties has been modification of the structure and composition of fibrin hydrogels. In this review, recent advances in composite fibrin scaffolds, chemically modified fibrin hydrogels, interpenetrated polymer network (IPN) hydrogels composed of fibrin and other synthetic or natural polymers are critically reviewed, focusing on their use for tissue engineering.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/29/ea/10.1177_20417314231190288.PMC10426312.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10355843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tissue engineering in growth plate cartilage regeneration: Mechanisms to therapeutic strategies.","authors":"Ruoyi Guo, Hanjie Zhuang, Xiuning Chen, Yulong Ben, Minjie Fan, Yiwei Wang, Pengfei Zheng","doi":"10.1177/20417314231187956","DOIUrl":"https://doi.org/10.1177/20417314231187956","url":null,"abstract":"<p><p>The repair of growth plate injuries is a highly complex process that involves precise spatiotemporal regulation of multiple cell types. While significant progress has been made in understanding the pathological mechanisms underlying growth plate injuries, effectively regulating this process to regenerate the injured growth plate cartilage remains a challenge. Tissue engineering technology has emerged as a promising therapeutic approach for achieving tissue regeneration through the use of functional biological materials, seed cells and biological factors, and it is now widely applied to the regeneration of bone and cartilage. However, due to the unique structure and function of growth plate cartilage, distinct strategies are required for effective regeneration. Thus, this review provides an overview of current research on the application of tissue engineering to promote growth plate regeneration. It aims to elucidates the underlying mechanisms by which tissue engineering promotes growth plate regeneration and to provide novel insights and therapeutic strategies for future research on the regeneration of growth plate.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f7/be/10.1177_20417314231187956.PMC10359656.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Augmented effect of fibroblast growth factor 18 in bone morphogenetic protein 2-induced calvarial bone healing by activation of CCL2/CCR2 axis on M2 macrophage polarization.","authors":"Worachat Namangkalakul, Shigenori Nagai, Chengxue Jin, Ken-Ichi Nakahama, Yuki Yoshimoto, Satoshi Ueha, Kazunari Akiyoshi, Kouji Matsushima, Tomoki Nakashima, Masaki Takechi, Sachiko Iseki","doi":"10.1177/20417314231187960","DOIUrl":"https://doi.org/10.1177/20417314231187960","url":null,"abstract":"<p><p>Fibroblast growth factor (FGF) signaling plays essential roles in various biological events. FGF18 is one of the ligands to be associated with osteogenesis, chondrogenesis and bone healing. The mouse critical-sized calvarial defect healing induced by the bone morphogenetic protein 2 (BMP2)-hydrogel is stabilized when FGF18 is added. Here, we aimed to investigate the role of FGF18 in the calvarial bone healing model. We first found that FGF18 + BMP2 hydrogel application to the calvarial bone defect increased the expression of anti-inflammatory markers, including those related to tissue healing M2 macrophage (M2-Mø) prior to mineralized bone formation. The depletion of macrophages with clodronate liposome hindered the FGF18 effect. We then examined how FGF18 induces M2-Mø polarization by using mouse primary bone marrow (BM) cells composed of macrophage precursors and BM stromal cells (BMSCs). In vitro studies demonstrated that FGF18 indirectly induces M2-Mø polarization by affecting BMSCs. Whole transcriptome analysis and neutralizing antibody treatment of BMSC cultured with FGF18 revealed that chemoattractant chemokine (c-c motif) ligand 2 (CCL2) is the major mediator for M2-Mø polarization. Finally, FGF18-augmented activity toward favorable bone healing with BMP2 was diminished in the calvarial defect in <i>Ccr2-</i>deleted mice. Altogether, we suggest a novel role of FGF18 in M2-Mø modulation via stimulation of CCL2 production in calvarial bone healing.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c2/72/10.1177_20417314231187960.PMC10387695.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10304672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jae Wan Suh, Kyoung-Mi Lee, Eun Ae Ko, Dong Suk Yoon, Kwang Hwan Park, Hyun Sil Kim, Jong In Yook, Nam Hee Kim, Jin Woo Lee
{"title":"Promoting angiogenesis and diabetic wound healing through delivery of protein transduction domain-BMP2 formulated nanoparticles with hydrogel.","authors":"Jae Wan Suh, Kyoung-Mi Lee, Eun Ae Ko, Dong Suk Yoon, Kwang Hwan Park, Hyun Sil Kim, Jong In Yook, Nam Hee Kim, Jin Woo Lee","doi":"10.1177/20417314231190641","DOIUrl":"https://doi.org/10.1177/20417314231190641","url":null,"abstract":"<p><p>Decreased angiogenesis contributes to delayed wound healing in diabetic patients. Recombinant human bone morphogenetic protein-2 (rhBMP2) has also been demonstrated to promote angiogenesis. However, the short half-lives of soluble growth factors, including rhBMP2, limit their use in wound-healing applications. To address this limitation, we propose a novel delivery model using a protein transduction domain (PTD) formulated in a lipid nanoparticle (LNP). We aimed to determine whether a gelatin hydrogel dressing loaded with LNP-formulated PTD-BMP2 (LNP-PTD-BMP2) could enhance the angiogenic function of BMP2 and improve diabetic wound healing. In vitro, compared to the control and rhBMP2, LNP-PTD-BMP2 induced greater tube formation in human umbilical vein endothelial cells and increased the cell recruitment capacity of HaCaT cells. We inflicted large, full-thickness back skin wounds on streptozotocin-induced diabetic mice and applied gelatin hydrogel (GH) cross-linked by microbial transglutaminase containing rhBMP2, LNP-PTD-BMP2, or a control to these wounds. Wounds treated with LNP-PTD-BMP2-loaded GH exhibited enhanced wound closure, increased re-epithelialization rates, and higher collagen deposition than those with other treatments. Moreover, LNP-PTD-BMP2-loaded GH treatment resulted in more CD31- and α-SMA-positive cells, indicating greater neovascularization capacity than rhBMP2-loaded GH or GH treatments alone. Furthermore, in vivo near-infrared fluorescence revealed that LNP-PTD-BMP2 has a longer half-life than rhBMP2 and that BMP2 localizes around wounds. In conclusion, LNP-PTD-BMP2-loaded GH is a viable treatment option for diabetic wounds.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/67/f6/10.1177_20417314231190641.PMC10434183.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10305939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In vivo vascularized scaffold with different shear-exposed models for lymphatic tissue regeneration.","authors":"Hui-Yi Hsiao, Gina Alicia Mackert, Yung-Chun Chang, Jia-Wei Liu, Frank Chun-Shin Chang, Jung-Ju Huang","doi":"10.1177/20417314231196212","DOIUrl":"https://doi.org/10.1177/20417314231196212","url":null,"abstract":"<p><p>Current clinical treatments on lymphedema provide promising results, but also result in donor site morbidities. The establishment of a microenvironment optimized for lymphangiogenesis can be an alternative way to enhance lymphatic tissue formation. Hemodynamic flow stimuli have been confirmed to have an influential effect on angiogenesis in tissue engineering, but not on lymphatic vessel formation. Here, the three <i>in vivo</i> scaffolds generated from different blood stimuli in the subcutaneous layer, in the flow through pedicle, and in an arterio-venous (AV) loop model, were created to investigate potential of lymphangiogenesis of scaffolds containing lymphatic endothelial cells (LECs). Our results indicated that AV loop model displayed better lymphangiogenesis in comparison to the other two models with slower flow or no stimuli. Other than hemodynamic force, the supplement of LECs is required for lymphatic vessel regeneration. The <i>in vivo</i> scaffold generated from AV loop model provides an effective approach for engineering lymphatic tissue in the clinical treatment of lymphedema.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fa/4d/10.1177_20417314231196212.PMC10472829.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10669331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhaohua Wang, Si Wen, Meiqi Zhong, Ziming Yang, Wei Xiong, Kuo Zhang, Shude Yang, Huizheng Li, Shu Guo
{"title":"Epigenetics: Novel crucial approach for osteogenesis of mesenchymal stem cells.","authors":"Zhaohua Wang, Si Wen, Meiqi Zhong, Ziming Yang, Wei Xiong, Kuo Zhang, Shude Yang, Huizheng Li, Shu Guo","doi":"10.1177/20417314231175364","DOIUrl":"https://doi.org/10.1177/20417314231175364","url":null,"abstract":"<p><p>Bone has a robust regenerative potential, but its capacity to repair critical-sized bone defects is limited. In recent years, stem cells have attracted significant interest for their potential in tissue engineering. Applying mesenchymal stem cells (MSCs) for enhancing bone regeneration is a promising therapeutic strategy. However, maintaining optimal cell efficacy or viability of MSCs is limited by several factors. Epigenetic modification can cause changes in gene expression levels without changing its sequence, mainly including nucleic acids methylation, histone modification, and non-coding RNAs. This modification is believed to be one of the determinants of MSCs fate and differentiation. Understanding the epigenetic modification of MSCs can improve the activity and function of stem cells. This review summarizes recent advances in the epigenetic mechanisms of MSCs differentiation into osteoblast lineages. We expound that epigenetic modification of MSCs can be harnessed to treat bone defects and promote bone regeneration, providing potential therapeutic targets for bone-related diseases.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/45/be/10.1177_20417314231175364.PMC10278427.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}