Materials Today Bio最新文献

{"title":"Modular iodinated carboxybetaine copolymers as charge-sensitive contrast agents for the detection of cartilage degradation","authors":"Patrick Weber ,&nbsp;Annalena Maier ,&nbsp;David Fercher,&nbsp;Maryam Asadikorayem,&nbsp;Marcy Zenobi-Wong","doi":"10.1016/j.mtbio.2024.101302","DOIUrl":"10.1016/j.mtbio.2024.101302","url":null,"abstract":"<div><div>Accurately assessing cartilage tissue degradation is a big challenge in osteoarthritis (OA) research, as histology only provides information about a 2D tissue section, and currently available contrast agents for tomographic evaluation suffer from low specificity. In this study, we present a modular platform based on zwitterionic carboxybetaine (CBAA) to create multivalent polymeric contrast agents for x-ray computed tomography (CT) with high specificity towards the anionic glycosaminoglycans in the cartilage tissue. By copolymerizing CBAA with different ratios of anionic and cationic iodinated comonomers, we created a library of polymers with net charges ranging from strongly anionic to strongly cationic. The polymers were applied onto osteochondral plugs with different degradation states and the resulting CT images compared to histological stainings. In healthy tissues, the bulk contrast enhancement was strongly correlated with polymer charge, with cationic polymers reaching a 2-fold stronger contrast compared to established small molecule contrast agents. While a further increase in cationic charge slowed the penetration, it increased the polymer's specificity, thereby enabling the most cationic polymer C40 (40 mol% cationic iodinated comonomer) to discriminate accurately between tissues treated with IL-1β for 0, 1, 2 and 3 weeks. Moreover, this polymer also showed a strong local specificity, visualizing local differences in GAG distribution with significantly increased accuracy compared to the controls. Our polymer contrast agents show the importance of multivalency and charge control for the accurate, volumetric detection of GAGs in the cartilage tissue and paves the way towards new contrast agents in- and outside of the clinic.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101302"},"PeriodicalIF":8.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in coaxial electrospun nanofibers for wound healing","authors":"Jing Zhao ,&nbsp;Liyun Chen ,&nbsp;Aiwei Ma ,&nbsp;Xujue Bai ,&nbsp;Yating Zeng ,&nbsp;Daojun Liu ,&nbsp;Bo Liu ,&nbsp;Wancong Zhang ,&nbsp;Shijie Tang","doi":"10.1016/j.mtbio.2024.101309","DOIUrl":"10.1016/j.mtbio.2024.101309","url":null,"abstract":"<div><div>The skin is the body's primary immune barrier, defending it against pathogenic invasion. Skin injuries impose a significant physiological burden on patients, making effective wound management essential. Dressings are commonly employed in wound care, and electrospun nanofiber dressings are a research hotspot owing to their ease of fabrication, cost-effectiveness, and structural similarity to the extracellular matrix. Coaxial electrospinning offers considerable advantages in drug delivery, fiber structure transformation, and enhanced interaction with the host. These attributes make coaxial electrospun materials promising candidates for precision and personalized wound dressings in medical treatments. This review provides a comprehensive overview of wound healing and its influencing factors. It also outlines coaxial electrospinning's production principles and benefits in wound dressings. Guided by the factors affecting wound healing, coaxial electrospun nanofiber dressings have different application modalities. Furthermore, we discuss the current limitations and future directions for enhancing the current coaxial electrospun dressing technologies.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101309"},"PeriodicalIF":8.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PH-sensitive adriamycin hydrochloride and oxaliplatin dual-loaded microspheres synergistically enhance local injections effect of hepatocellular carcinoma","authors":"Jialu Weng ,&nbsp;Shiyi Wu ,&nbsp;Yating Pan ,&nbsp;Yifan Lai ,&nbsp;Jinrong Zhu ,&nbsp;Wenzhang Jin ,&nbsp;Deyu Lu ,&nbsp;Yizhang Chen ,&nbsp;Zhijie Yu ,&nbsp;Xinjie Zan ,&nbsp;Jinglin Xia","doi":"10.1016/j.mtbio.2024.101311","DOIUrl":"10.1016/j.mtbio.2024.101311","url":null,"abstract":"<div><div>Chemotherapy is the primary palliative treatment for advanced hepatocellular carcinoma (HCC). However, the systemic delivery is associated with the drawbacks including a high risk of adverse effects and a low efficacy. Therefore, local injection therapy may be beneficial. Nevertheless, the existing local drug-carrying microspheres(DOBM)have the characteristics of low loading and abrupt release, can not simultaneously load two drugs, and may cause unnecessary toxicity. In this study, we created the dual-loaded bovine serum albumin (BSA) microspheres (also known as DOBM), which were hollow and contained both oxaliplatin (OXA) and Adriamycin hydrochloride (DOX). In addition, this pH-sensitive drug delivery method exhibited a high drug loading capacity and was promising in breaking through biological barriers, making it a viable option for the treatment of HCC through local implantation. Based on physiochemical evaluation of BSA microspheres, they had a porous structure which was close to the surface. Adriamycin and oxaliplatin were successfully added to the surface of BSA microspheres. According to in vitro experimental results, the growth of human HCC (HCC-LM3 and PLC/PRF/5) cell lines was significantly inhibited by DOBM. Furthermore, in the subcutaneous PLC/PRF/5 HCC model, DOBM played an essential role in tumor development and change in the tumor microenvironment.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101311"},"PeriodicalIF":8.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogel local drug delivery systems for postsurgical management of tumors: Status Quo and perspectives","authors":"Ziqiao Zhong ,&nbsp;Lu Gan ,&nbsp;Ziyi Feng ,&nbsp;Wenhao Wang ,&nbsp;Xin Pan ,&nbsp;Chuanbin Wu ,&nbsp;Ying Huang","doi":"10.1016/j.mtbio.2024.101308","DOIUrl":"10.1016/j.mtbio.2024.101308","url":null,"abstract":"<div><div>Surgery is one of the primary treatments for solid tumors. However, the incomplete resection of tumor cells and the immunosuppressive microenvironment make the issue of postsurgical tumor recurrence a great challenge. Furthermore, a wide range of requirements, including ensuring effective hemostasis, implementing prophylactic measures against infection, and promoting wound healing, were also raised in the postsurgical management of tumors. To fulfill these demands, multiple hydrogel local drug delivery systems (HLDDS) were developed recently. These HLDDS are expected to offer numerous advantages in the postsurgical management of tumors, such as achieving high local drug concentrations at the lesion, efficient delivery to surgical microcavities, mitigating systemic side effects, and addressing the diverse demand. Thus, in this review, a detailed discussion of the diverse demands of postsurgical management of tumors is provided. And the current publication trend on HLDDS in the postsurgical management of tumors is analyzed and discussed. Then, the applications of different types of HLDDS, <em>in-situ</em> HLDDS and <em>non-in-situ</em> HLDDS, in postsurgical management of tumors were introduced and summarized. Besides, the current problems and future perspectives are discussed. The review is expected to provide an overview of HLDDS in postsurgical management of tumors and promote their clinical application.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101308"},"PeriodicalIF":8.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sericin coats of silk fibres, a degumming waste or future material?","authors":"Yunong Yuan ,&nbsp;Mohammad Nasri ,&nbsp;Azadeh Manayi ,&nbsp;Junying Zhang ,&nbsp;Chunyong Wu ,&nbsp;Tae-Joon Jeon ,&nbsp;Lifeng Kang","doi":"10.1016/j.mtbio.2024.101306","DOIUrl":"10.1016/j.mtbio.2024.101306","url":null,"abstract":"<div><div>Silk is a fibrous biopolymer with a recorded history in the textile industries for centuries. This fibre is constituted of two different proteins: fibroin and sericin, of which the latter accounting for approximately 20–30 % of the silk mass. Silk sericin (SSER) was previously considered as a waste by-product in silk fibroin extraction. SSER has recently garnered significant scientific interest due to its extensive biological and pharmacological properties. These include antioxidant effects, biocompatibility, low immunogenicity, controlled biodegradability, and the ability to induce cell proliferation. This review covers studies about various aspects of this emerging material, namely, its general morphology, specific structure, molecular weight, features of different layers, and gene sequences. The impact of different extraction methods and the application of extracted SSER based on molecular weight are discussed. Additionally, the characteristic functional groups in the amino acids of sericin facilitate its applications in regenerative medicine, wound healing, drug delivery, textile, environment, and energy, in various forms like hydrogels, films, scaffolds, and conduits. SSER-based materials offer great potentials for multi-functional applications in the upcoming decades, showcasing adaptability for various functional uses and promising future technological advancements.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101306"},"PeriodicalIF":8.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Procyanidin capsules provide a new option for long-term ROS scavenging in chronic inflammatory diseases","authors":"Linxiao Sun ,&nbsp;Shaoyin Wei ,&nbsp;Chenglong Wang ,&nbsp;Yipiao Zhang ,&nbsp;Xingjie Zan ,&nbsp;Lianxin Li ,&nbsp;Chunwu Zhang","doi":"10.1016/j.mtbio.2024.101310","DOIUrl":"10.1016/j.mtbio.2024.101310","url":null,"abstract":"<div><div>Chronic inflammatory diseases such as diabetic wounds and osteoarthritis are significant threats to human health. Failure to scavenge longstanding excessive reactive oxygen species (ROS) is an important cause of chronic inflammatory diseases, yet existing treatments that provide long-lasting therapeutic effects are limited. Here, procyanidin capsules were synthesized in a simple one-step way using calcium carbonate as a template. The biosafety of procyanidin capsules <em>in vitro</em> and <em>in vivo</em> was monitored by cytotoxicity and pathological sections. The therapeutic effect of procyanidin capsules in diabetic wounds and osteoarthritis was accessed by pathological evaluation combined with the quantification of inflammatory markers. The data showed that procyanidin capsules could long-term scavenge excessive ROS and effectively promote articular cartilage repair in osteoarthritis, accelerating diabetic wound healing. Lastly, transcriptome analysis suggested that procyanidin capsules commonly regulated adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) signaling in diabetic wounds and osteoarthritis. This study provides a straightforward protocol for creating procyanidin capsules, while presenting a promising new therapeutic option for long-term scavenging ROS in chronic inflammatory diseases.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101310"},"PeriodicalIF":8.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biodegradable exosome-engineered hydrogels for the prevention of peritoneal adhesions via anti-oxidation and anti-inflammation","authors":"Weitong Wang ,&nbsp;Yuchen Ren ,&nbsp;Qingyu Yu ,&nbsp;Lijie Jiang ,&nbsp;Chaojie Yu ,&nbsp;Zhiwei Yue ,&nbsp;Yue Wang ,&nbsp;Jiajun Lu ,&nbsp;Pengcheng Che ,&nbsp;Junjie Li ,&nbsp;Hong Sun","doi":"10.1016/j.mtbio.2024.101312","DOIUrl":"10.1016/j.mtbio.2024.101312","url":null,"abstract":"<div><div>Peritoneal adhesions (PA) are a common and severe complication after abdominal surgery, impacting millions of patients worldwide. The use of anti-adhesion materials as physical barriers is an effective strategy to prevent postoperative adhesions. However, the local inflammatory microenvironment exerts a significant impact on the efficacy of anti-adhesion therapies. In this study, an injectable hydrogel based on oxidized dextran/carboxymethyl chitosan (DCC) is designed and prepared. Furthermore, the DCC hydrogel is specifically engineered to load the adipose mesenchymal stem cells (ADSCs)-derived exosomes (Exos) for the treatment of PA. The prepared DCC hydrogel can act as the physical barrier via covering the irregular wound surface effectively. Moreover, it shows controlled degradation property, enabling the regulated release of Exos. The DCC hydrogel loaded Exos (DCC/Exo) system has high antioxidant capacity, and can effectively modulate the inflammatory microenvironments and diminish apoptosis. Notably, it promotes a polarization shift towards the M2-like phenotype in macrophages. The RNA-seq analysis confirms that the DCC/Exo system exhibits significant anti-inflammatory properties and promotes a reduction in collagen deposition. Consequently, the DCC/Exo system can inhibit peritoneal adhesions significantly in a mouse cecum-abdominal wall injury model. These results demonstrate the DCC/Exo is an ideal material for preventing postoperative adhesions.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101312"},"PeriodicalIF":8.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in arthropod-inspired bionic materials for wound healing","authors":"Yuchen Li ,&nbsp;Jiaming Cui ,&nbsp;Di Xiao ,&nbsp;Bixuan Cao ,&nbsp;Jing Wei ,&nbsp;Qian Wang ,&nbsp;Junwei Zong ,&nbsp;Jinwu Wang ,&nbsp;Mingzhi Song","doi":"10.1016/j.mtbio.2024.101307","DOIUrl":"10.1016/j.mtbio.2024.101307","url":null,"abstract":"<div><div>Arthropods contain lots of valuable bionic information from the composition to the special structure of the body. In particular, the rapid self-healing ability and antibacterial properties are amazing. Biomimetic materials for arthropods have been helpful methods for wound management. Here, we have identified four major dimensions needed to create biomimetic materials for arthropods, including ingredient, behavior, structure and internal reaction. According to different dimensions, we classify and introduce the reported arthropod biomimetic materials. Antibacterial, hemostatic and healing promotion are the main functions of the active compositions of arthropods developed by humans, and most of them play a drug effect. We believe that an ideal biomimetic material of arthropod should have the effect on promoting wound healing through the advantages of structure and composition. The special macroscopic and microscopic structure of the epidermis may provide good mechanical support for biomimetic materials. The drug release regularity in the bionic materials can be referred to the aggressive and secretory behavior of arthropods. The synthesis of substances in arthropods is also noteworthy, and we can learn these special reactions to complete the fast preparation of materials. Arthropod-inspired bionic materials have broad innovation and application prospects in the field of wound repair.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101307"},"PeriodicalIF":8.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adhesive lipophilic gels delivering rapamycin prevent oral leukoplakia from malignant transformation","authors":"Yuqi Du ,&nbsp;Tiannan Liu ,&nbsp;Tingting Ding ,&nbsp;Xin Zeng ,&nbsp;Qianming Chen ,&nbsp;Hang Zhao","doi":"10.1016/j.mtbio.2024.101305","DOIUrl":"10.1016/j.mtbio.2024.101305","url":null,"abstract":"<div><div>Oral leukoplakia (OLK) is the most emblematic oral potentially malignant disorder that may precede the diagnosis of oral squamous cell carcinoma (OSCC) and has an overall malignant transformation rate of 9.8 %. Early intervention is crucial to reduce the malignant transformation rate from OLK to OSCC but the lack of effective local pharmaceutical preparations poses a challenge to clinical management. Rapamycin is speculated to prevent OLK from carcinogenesis and its inherent lipophilicity facilitates its penetration into stratum corneum. Nevertheless, hydrophilic hydrogels frequently encounter challenges when attempting to deliver lipophilic drugs. Furthermore, the oral cavity presents a complex environment defined by oral motor functions, saliva secretion cycles, dynamic fluctuations, and protective barriers comprising mucus and lipid layers. Consequently, addressing issues of muco-penetration and muco-adhesion is imperative for developing an effective drug delivery system aiming at delivering rapamycin to target oral potentially malignant disorders.</div><div>Here, a dual-function hydrogel drug delivery system integrating adhesion and lipophilicity was successfully developed based on polyvinyl alcohol (PVA) and dioleoyl phosphatidylglycerol (DOPG) via dynamic boronic ester bonds. Rheological experiments based on orthogonal design revealed that PVA-DOPG hydrogels exhibited ideal adhesive strength (around 6 kPa) and could adhere to various surfaces in both dry and wet conditions. PVA-DOPG hydrogels also significantly promoted lipophilic molecules’ penetration into stratum corneum (integrated fluorescence density of 6.95 ± 0.52 × 10⁶ and mean fluorescence depth of 0.96 ± 0.07 mm) of ex-vivo porcine buccal mucosa (<em>p</em> &lt; 0.001). Furthermore, PVA-DOPG hydrogels incorporating rapamycin inhibited malignant transformation of OLK mouse model induced by 4-Nitroquinoline N-oxide (4-NQO), distinct improvements in survival (the neoplasm incidence density at the 40th day is 0.0091) (<em>p</em> &lt; 0.05), decrease in neoplasm incidence density of 36.36 % and inhibition rate in neoplasm volume of 75.04 ± 33.67 % have been demonstrated, suggesting the hydrogels were valuable candidates for potential applications in the management of OLK.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101305"},"PeriodicalIF":8.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The considerations on selecting the appropriate decellularized ECM for specific regeneration demands","authors":"Shihan Zhang ,&nbsp;Yaru Guo ,&nbsp;Yixuan Lu ,&nbsp;Fangyong Liu ,&nbsp;Boon Chin Heng ,&nbsp;Xuliang Deng","doi":"10.1016/j.mtbio.2024.101301","DOIUrl":"10.1016/j.mtbio.2024.101301","url":null,"abstract":"<div><div>An ideal biomaterial should create a customized tissue-specific microenvironment that can facilitate and guide the tissue repair process. Due to its good biocompatibility and similar biochemical properties to native tissues, decellularized extracellular matrix (dECM) generally yields enhanced regenerative outcomes, with improved morphological and functional recovery. By utilizing various decellularization techniques and post-processing protocols, dECM can be flexibly prepared in different states from various sources, with specifically customized physicochemical properties for different tissues. To initiate a well-orchestrated tissue-regenerative response, dECM exerts multiple effects at the wound site by activating various overlapping signaling pathways to promote cell adhesion, proliferation, and differentiation, as well as suppressing inflammation via modulation of various immune cells, including macrophages, T cells, and mastocytes. Functional tissue repair is likely the main aim when employing the optimized dECM biomaterials. Here, we review the current applications of different kinds of dECMs in an attempt to improve the efficiency of tissue regeneration, highlighting key considerations on developing dECM for specific tissue engineering applications.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101301"},"PeriodicalIF":8.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}