Yanan Jing , Guidan Wang , Ruolin Shi , Wenjing Wen , Wenjie Wang , Xuan Zhao , Gaofeng Liang
{"title":"Novel microsphere scaffold-based islet organoids for rescuing type 1 diabetes and reversing hyperglycemia","authors":"Yanan Jing , Guidan Wang , Ruolin Shi , Wenjing Wen , Wenjie Wang , Xuan Zhao , Gaofeng Liang","doi":"10.1016/j.engreg.2025.05.001","DOIUrl":"10.1016/j.engreg.2025.05.001","url":null,"abstract":"<div><div>Type 1 diabetes (T1D) is an autoimmune deficiency disease characterized by elevated blood sugar levels and insulin resistance, leading to various adverse health effects and complications, such as diabetic cardiomyopathy and diabetic ketoacidosis. Currently, T1D is primarily treated through organoid transplantation and extracorporeal insulin injection. However, the clinical utility of these treatments is limited by increased systemic immunosuppression due to graft donor shortages and the side effects associated with exogenous insulin therapy. Recently, the emergence of bioengineered islet-like organs has opened up possibilities for constructing insulin-secreting cells in vitro to treat insulin-dependent diabetes. In this study, we developed a novel microsphere scaffold-based islet cell spheroid culture system that integrates islet organoids with 3D microsphere scaffolds, enabling the consistent generation of 3D islet cell spheroids. Following transplantation into the renal capsule of diabetic mice, these organoids demonstrated significant hypoglycemic effects, with detectable insulin secretion in the serum. On day 30 post-transplantation, β-cell marker expression was significantly increased in the grafts. We further investigated the glucose-related proteins that microsphere scaffold-based islet organoids may regulate. Our findings confirm that islet-like organoids can effectively secrete insulin and play a role in maintaining blood sugar stability. These results indicate that islet-like organs generated via microsphere scaffolds exhibit similar endocrine functions to those of natural islets, can survive in the host body for extended periods, and can effectively exert hypoglycemic effects, thereby providing a solid foundation for the application of islet-like organs in type 1 diabetes research.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"6 1","pages":"Pages 121-132"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hun Jin Jeong, Alia Koch, Soomin Park, Solaiman Tarafder, Chang H. Lee
{"title":"Bioactive scaffolds integrated with micro-precise spatiotemporal delivery and in vivo degradation tracking for complex tissue regeneration","authors":"Hun Jin Jeong, Alia Koch, Soomin Park, Solaiman Tarafder, Chang H. Lee","doi":"10.1016/j.engreg.2025.01.001","DOIUrl":"10.1016/j.engreg.2025.01.001","url":null,"abstract":"<div><div>Three-dimensional (3D) printing has evolved to incorporate controlled delivery systems to guide the regeneration of complex tissues, with limited clinical translation. The challenges include the limited precision in spatiotemporal delivery and poorly understood <em>in vivo</em> scaffold degradation rates. Here, we report auspicious preclinical outcomes in the functional regeneration of temporomandibular joint (TMJ) discs of mini-pigs. TMJ disc has been an extremely challenging target for regenerative engineering given the uniquely heterogeneous matrix distribution and region-variant anisotropic orientation. We optimally implemented advanced 3D printing technologies with micro-precise spatiotemporal delivery to build anatomically correct, bioactive scaffolds with native-like regionally variant microstructure and mechanical properties. We also applied quantum dots (QDs) labeling of scaffolds to enable non-invasive <em>in vivo</em> degradation tracking. In mini-pigs, the scaffold implantation upon discectomy has successfully led to <em>in-situ</em> regeneration of TMJ discs by 3 months, exhibiting native-like heterogeneity and multi-scale mechanical properties without any sign of cartilage damage. In addition, our non-invasive imaging resulted in reliable <em>in vivo</em> tracking of scaffold degradation, exhibiting notably different degradation rates between individual animals. Our findings suggest a significant translational potential of our cell-free, bioactive scaffolds equipped with non-invasive tracking modality for in-situ tissue engineering of TMJ discs.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"6 ","pages":"Pages 34-44"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanan Jing , Guidan Wang , Ruolin Shi , Wenjing Wen , Wenjie Wang , Xuan Zhao , Gaofeng Liang
{"title":"Novel microsphere scaffold-based islet organoids for rescuing type 1 diabetes and reversing hyperglycemia","authors":"Yanan Jing , Guidan Wang , Ruolin Shi , Wenjing Wen , Wenjie Wang , Xuan Zhao , Gaofeng Liang","doi":"10.1016/j.engreg.2025.05.001","DOIUrl":"10.1016/j.engreg.2025.05.001","url":null,"abstract":"<div><div>Type 1 diabetes (T1D) is an autoimmune deficiency disease characterized by elevated blood sugar levels and insulin resistance, leading to various adverse health effects and complications, such as diabetic cardiomyopathy and diabetic ketoacidosis. Currently, T1D is primarily treated through organoid transplantation and extracorporeal insulin injection. However, the clinical utility of these treatments is limited by increased systemic immunosuppression due to graft donor shortages and the side effects associated with exogenous insulin therapy. Recently, the emergence of bioengineered islet-like organs has opened up possibilities for constructing insulin-secreting cells in vitro to treat insulin-dependent diabetes. In this study, we developed a novel microsphere scaffold-based islet cell spheroid culture system that integrates islet organoids with 3D microsphere scaffolds, enabling the consistent generation of 3D islet cell spheroids. Following transplantation into the renal capsule of diabetic mice, these organoids demonstrated significant hypoglycemic effects, with detectable insulin secretion in the serum. On day 30 post-transplantation, β-cell marker expression was significantly increased in the grafts. We further investigated the glucose-related proteins that microsphere scaffold-based islet organoids may regulate. Our findings confirm that islet-like organoids can effectively secrete insulin and play a role in maintaining blood sugar stability. These results indicate that islet-like organs generated via microsphere scaffolds exhibit similar endocrine functions to those of natural islets, can survive in the host body for extended periods, and can effectively exert hypoglycemic effects, thereby providing a solid foundation for the application of islet-like organs in type 1 diabetes research.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"6 ","pages":"Pages 121-132"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Greg Sacks, Vincent DeStefano, Claire Parker, Ryan Lebens, Harry Mushlin
{"title":"Corrigendum to “The Artificial Disc Nucleus and Other Strategies for Replacement of the Nucleus Pulposus: Past, Present and Future Designs for an Emerging Surgical Solution” [Engineered Regeneration 5(2024), 269-281]","authors":"Greg Sacks, Vincent DeStefano, Claire Parker, Ryan Lebens, Harry Mushlin","doi":"10.1016/j.engreg.2024.12.001","DOIUrl":"10.1016/j.engreg.2024.12.001","url":null,"abstract":"","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"5 4","pages":"Page 521"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yang Yu , Yinxiang Tang , Weiwen Liang , Yuanbin Wang , Yang Ouyang , Wenxuan Xiong , Bingna Zheng , Lili Chu , Hui Wang
{"title":"Asymmetric porous composite hydrogel patch for microenvironment-adapted repair of contaminated abdominal wall defects","authors":"Yang Yu , Yinxiang Tang , Weiwen Liang , Yuanbin Wang , Yang Ouyang , Wenxuan Xiong , Bingna Zheng , Lili Chu , Hui Wang","doi":"10.1016/j.engreg.2024.03.004","DOIUrl":"10.1016/j.engreg.2024.03.004","url":null,"abstract":"<div><div>Effective antibacterial property and long-term mechanical support are essential for the repair of complex abdominal wall defects associated with infection. However, clinically available repair materials often fail to meet these requirements, resulting in high surgical failure rate and complications. In this study, an asymmetric porous composite hydrogel patch (cCS/PVA@BAC) with antibacterial, anti-adhesion, pro-healing, and durable mechanical support properties is designed for the efficient repair of contaminated abdominal wall defects. By stepwise phase-conversion and soaking method, robust and stable polyvinyl alcohol hydrogel (PVAH) is integrated with the biocompatible multicomponent hydrogel made of chitosan and carboxymethyl chitosan (cCS), and benzalkonium chloride (BAC) is loaded to enhance the antibacterial property. The cCS layer of cCS/PVA@BAC has an extracellular matrix-like porous structure, which can promote fibroblasts adhesion and wound healing. In contrast, the PVAH layer on the other side with a smooth and dense structure, which can reduce fibroblasts adhesion and prevent visceral adhesion. In addition, the composite hydrogel patch has good anti-swelling and anti-deformation properties as well as stable mechanical strength, thus can withstand high intraperitoneal pressure in the wet internal microenvironment. The loaded BAC can efficiently kill bacteria and improve the local inflammatory microenvironment. With these advantages, cCS/PVA@BAC can significantly reduce inflammation, promote tissue remodeling, and accelerate the healing of contaminated abdominal wall defects in the rat model. These findings suggest a potential use of multifunctional hydrogel patch as an ideal material for effective repair of contaminated soft tissue defects.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"5 4","pages":"Pages 468-481"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140756844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jésica I. Zuchuat , Adriana S. Manzano , Valeria Sigot , Gastón L. Miño , Oscar A. Decco
{"title":"Bone improvement in osteoporotic rabbits using CoCrMo implants","authors":"Jésica I. Zuchuat , Adriana S. Manzano , Valeria Sigot , Gastón L. Miño , Oscar A. Decco","doi":"10.1016/j.engreg.2024.05.002","DOIUrl":"10.1016/j.engreg.2024.05.002","url":null,"abstract":"<div><div>The management of bone repair in patients with osteoporosis depends on the clinical situation and the extent of the damage. The repair of bone lesions by inducing new bone formation is important for maintaining bone architecture and density. Herein, we reported the use of Cobalt Chromium Molybdenum (CoCrMo) implants in osteoporotic rabbits and the regenerative outcomes <em>in vivo</em>. The aim was to determine whether the placement of CoCrMo plates would induce qualitative and quantitative differences in the osteoporotic tissue beneath and surrounding the implant. We assessed the effect of the alloy in the bone of animals receiving implants for 4 and 8 weeks and compared the results to those of the osteoporotic non-implanted bone and the healthy controls. After 4 weeks, minimal histological changes were observed, whereas after 8 weeks a marked osteogenesis was evident with both apposition and substitution of new bone. In addition, a greater number of Haversian canals with increased canal area and decreased intracortical pores were observed in the implanted <em>vs</em> non implanted limb for both experimental groups. We show for the first time that the use of CrCoMo plates induces bone formation under osteoporotic conditions. The beneficial effect is localised on the cortical bone in areas in contact with the material. Although this effect may not directly influence the OP disease itself, it has direct implications for new bone formation adjacent to the biomaterial. This potential enhancement could play a crucial role in improving implant fixation in compromised bone, offering increased biocompatibility and stability.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"5 4","pages":"Pages 495-504"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141133439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiuhong Huang , Meimei Fu , Min Lu , Xiaoxian Wu , Weiqian David Hong , Xiaoying Wang , Panpan Wu , Keke Wu
{"title":"Polyphenol-based photothermal nanoparticles with sprayable capability for self-regulation of microenvironment to accelerate diabetic wound healing","authors":"Xiuhong Huang , Meimei Fu , Min Lu , Xiaoxian Wu , Weiqian David Hong , Xiaoying Wang , Panpan Wu , Keke Wu","doi":"10.1016/j.engreg.2024.05.003","DOIUrl":"10.1016/j.engreg.2024.05.003","url":null,"abstract":"<div><div>Current treatments for diabetic wounds have some curative effect, but the process is complicated and lack user-friendly wound dressings. Nanozymes have gained significant attention for wound healing due to their striking merits. Herein, we have developed a novel sprayable tannin acid-cobalt coordination nanozyme (TACo) for diabetic wound healing. TACo nanozyme offers a convenient and efficient methods by spraying directly onto wounds surface, reducing infection risk by avoiding direct contact. Notably, its antioxidant properties contribute to scavenging the reactive oxygen species (ROS), alleviating oxidative stress and inflammation of wound microenvironment. Additionally, TACo nanozyme could promote cell survival and multiplication, which is crucial for the wound healing process. Importantly, TACo nanozyme facilitates angiogenesis by enhancing cell viability, migration, and tube formation. The unique coordination between metal and phenolic components confers pH-responsive cobalt ion and TA release properties, avoiding secondary damage during the wound cleaning. This unique composition seamlessly integrates photothermal antibacterial therapy, inflammatory microenvironment management, supporting for angiogenesis, and effective promotion of extracellular matrix production sequentially by harnessing the acidic pH environment of diabetic wounds. In conclusion, the development of a sprayable TACo nanozyme presents a promising therapeutic approach for the treatment of diabetic wounds, addressing the complexities of current treatments and providing a user-friendly application method.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"5 4","pages":"Pages 505-520"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141401788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenwen Qi , Lei Shi , Xinhao Wu , Fangyuan Zhu , Zhenxiao Teng , Xiaochen Gao , Xin Bing , Na Guo , Xue Cao , Chengzhilin Li , Houyang Hu , Fanyu Yuan , Yuhan Dong , Ming Xia , Chengcheng Liu
{"title":"Bis-5HT modified Paris Saponin II nanoparticles treat neutrophil infiltrating allergic rhinitis by regulating the alanine metabolism pathway","authors":"Wenwen Qi , Lei Shi , Xinhao Wu , Fangyuan Zhu , Zhenxiao Teng , Xiaochen Gao , Xin Bing , Na Guo , Xue Cao , Chengzhilin Li , Houyang Hu , Fanyu Yuan , Yuhan Dong , Ming Xia , Chengcheng Liu","doi":"10.1016/j.engreg.2024.02.004","DOIUrl":"10.1016/j.engreg.2024.02.004","url":null,"abstract":"<div><div>Allergic rhinitis (AR) has emerged as a global concern, particularly due to the recent rise in disease incidence. There is an urgent need for safer, more effective, and shorter-term targeted immunotherapy approaches. Our previous studies have demonstrated the potential of paris saponins II in mitigating neutrophil infiltration in the nasal mucosa of AR mice. However, its clinical applicability has been hampered by limited by bio availability and bioactivity. In response to these limitations, we have developed bis-5HT-modified paris saponins II (designated as PLGA-5HT-PSII-Ce6) to target neutrophil-specific myeloperoxidase. Our verification, using metabolomics and other techniques, has affirmed the enhanced therapeutic efficacy of this targeted drug for allergic rhinitis. Furthermore, the incorporation of photosensitizers has improved the treatment effect particularly when light induction is introduced. This development lead to promising prospects for the treatment of AR.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"5 4","pages":"Pages 452-467"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143094066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guang Yang , Zili Guo , Xiangfeng Zhang , Jiayu Chen , Jie Weng , Jiapeng Bao , Xiaohua Yu
{"title":"Novel injectable composite incorporating denosumab promotes bone regeneration via bone homeostasis regulation","authors":"Guang Yang , Zili Guo , Xiangfeng Zhang , Jiayu Chen , Jie Weng , Jiapeng Bao , Xiaohua Yu","doi":"10.1016/j.engreg.2024.05.001","DOIUrl":"10.1016/j.engreg.2024.05.001","url":null,"abstract":"<div><div>Repair of large bone defects remains to be clinically challenging, yet current bone repair strategies focus on optimizing the osteogenic capacity of bone grafts, while the role of osteoclasts in bone regeneration has been largely ignored. Herein, we designed a injectable self-curing bone grafting paste capable of regulating both anabolic/catabolic activities during bone healing by immobilizing the RANKL inhibitor denosumab on dermal-derived extracellular matrix (ECM) microfibres, which were then incorporated into an injectable paste via a hydration reaction between β-tricalcium phosphate (β-TCP), monocalcium phosphate monohydrate (MCPM) and calcium sulfate hemihydrate (CSH). The incorporation of ECM microfibres not only serves as a sustained-release denosumab carrier to inhibit osteoclastogenesis but also improves the mechanical properties of the resulting composite by increasing the interaction between the organic and inorganic phases. <em>In vitro</em>, calcium supply from the composite along with ECM enhanced osteogenic differentiation of BMSC while release of denosumab effectively inhibits osteoclast fusion and alleviate osteoclastic activity. <em>In vivo</em>, it was observed that CSH/CP@ECM-Deno significantly reduced the number of osteoclasts, slowed down the process of bone resorption, and accelerated collagen deposition to promote new bone generation. These results suggest that modulation of osteoclastogenesis by interfering with bone homeostasis may be an effective bone repair strategy.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"5 4","pages":"Pages 482-494"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141026424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liqin Chen , Ying Zhang , Kexin Wang , Meixian Jin , Qi Chen , Simin Wang , Wei Hu , Zhai Cai , Yang Li , Shao Li , Yi Gao , Shuqin Zhou , Qing Peng
{"title":"A patch comprising human umbilical cord-derived hydrogel and mesenchymal stem cells promotes pressure ulcer wound healing","authors":"Liqin Chen , Ying Zhang , Kexin Wang , Meixian Jin , Qi Chen , Simin Wang , Wei Hu , Zhai Cai , Yang Li , Shao Li , Yi Gao , Shuqin Zhou , Qing Peng","doi":"10.1016/j.engreg.2024.10.002","DOIUrl":"10.1016/j.engreg.2024.10.002","url":null,"abstract":"<div><div>Pressure ulcers (PUs) are common skin injuries known for their high morbidity, rapid onset, susceptibility to infection, and challenging healing process. One potential therapy for PUs is cell-based therapy using mesenchymal stem cells (MSCs). However, poor survival and low cell retention of MSCs on skin lesions limit their therapeutic effects and applications. In this study, we prepared an extracellular matrix (dECM) hydrogel decellularized from the human umbilical cord (UC). A patch composed of UC-dECM and UC-MSCs was employed in the treatment of PUs in C57BL/6 mice. Our results indicate that the UC-dECM hydrogel effectively sustains cell viability, enhances the stemness-related gene expression in UC-MSCs, and promotes human umbilical vein endothelial cells (HUVECs) migration and angiogenesis. Compared to the groups treated with the patch containing only UC-dECM, injection of UC-MSCs or gauze dressing, the patch combining UC-dECM hydrogel with UC-MSCs significantly accelerated PU healing. This positive outcome can be attributed to the promotion of tissue re-epithelialization, collagen deposition, angiogenesis, and inflammation inhibition. Our results suggest that the composite patch, comprised of UC-dECM hydrogel and UC-MSCs, may be a promising therapeutic approach for PU treatment.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"5 4","pages":"Pages 433-442"},"PeriodicalIF":0.0,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}