George A Loxley, Consuelo Coser, Amir M Ghaemmaghami, Jing Yang
{"title":"Long-term interleukin-4 release from 3D printable affinity hydrogels promotes M2-like macrophage polarisation <i>in vitro</i>.","authors":"George A Loxley, Consuelo Coser, Amir M Ghaemmaghami, Jing Yang","doi":"10.1039/d4bm01623h","DOIUrl":"https://doi.org/10.1039/d4bm01623h","url":null,"abstract":"<p><p>The biopharmaceutical industry for engineered protein drugs is rapidly increasing in size but there is a lack of controlled release vehicles to enable targeted delivery for regenerative medicine applications. In this study, we used photocrosslinkable 3-sulfopropyl acrylate potassium salt (SPAK)-poly(ethylene glycol) diacrylate (PEGDA) hydrogels to achieve controlled release of lysozyme for 70 days with zero-order release and tuneable release rate. Scaling down hydrogel volume and protein loading concentration to release Transforming growth factor beta-1 (TGF-β1) and Interleukin-4 (IL-4) resulted in low cumulative release, even without SPAK. Increasing PEGDA molecular weight from 4 kDa to 20 kDa improved TGF-β1 release but it still remained below 10% after 10 days. We observed sustained IL-4 release in the therapeutic ng mL<sup>-1</sup> range for 73 days when loading IL-4 to 5% SPAK-10% PEGDA post photocrosslinking. Released IL-4 maintained bioactivity, promoting M2-like polarisation of THP-1 macrophages with day 53 supernatant, modelling long-term immunomodulation <i>in vitro</i>. We manufactured SPAK-PEGDA hydrogels by projection micro stereolithography, in which 3D printed 5% SPAK-10% PEGDA had an increased lysozyme release rate compared to its cast counterpart. 3D printed 5% SPAK-10% PEGDA with porous 3D design had an increased lysozyme release rate compared to a volume matched non-porous design. These findings highlight the potential of SPAK-PEGDA hydrogels for long-term cytokine delivery and show proof-of-concept for manipulating protein release kinetics with 3D printed hydrogel design.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multifunctional biomimetic liposomal nucleic acid scavengers inhibit the growth and metastasis of breast cancer.","authors":"Yuhang Miao, Kaizhen Wang, Xin Liu, Xin Wang, Yanwei Hu, Zhenwei Yuan, Dawei Deng","doi":"10.1039/d4bm01721h","DOIUrl":"https://doi.org/10.1039/d4bm01721h","url":null,"abstract":"<p><p>Chemotherapy and surgery, though effective in cancer treatment, trigger the release of nucleic acid-containing pro-inflammatory compounds from damaged tumor cells, known as nucleic acid-associated damage-associated molecular patterns (NA-DAMPs). This inflammation promotes tumor metastasis, and currently, no effective treatment exists for this treatment-induced inflammation and subsequent tumor metastasis. To address this challenge, we developed a biomimetic liposome complex (Lipo-Rh<sub>2</sub>) incorporating a hybrid structure of liposomes and dendritic polymers, mimicking cell membrane morphology. Lipo-Rh<sub>2</sub> leverages the multivalent surface properties of dendritic polymers to clear cell-free nucleic acids while serving as both a structural stabilizer and targeting ligand <i>via</i> embedded ginsenoside Rh<sub>2</sub>. Experimental data show that Lipo-Rh<sub>2</sub> effectively reduces free nucleic acids in mouse serum through charge interactions, downregulates Toll-like receptor expression, decreases inflammatory cytokine secretion, and inhibits both primary tumor growth and metastasis. Compared to the current nucleic acid scavenger PAMAM-G3, Lipo-Rh<sub>2</sub> demonstrates stronger antitumor effects, lower toxicity, and enhanced targeting capabilities. This biomimetic liposome-based nucleic acid scavenger represents a novel approach to nucleic acid clearance, expanding the framework for designing effective therapeutic agents.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Céline Bastard, Jann Carl-Theodor Schulte, Md Asaduzzaman, Calvin Hohn, Yonca Kittel, Laura De Laporte, Ronald Gebhardt
{"title":"Casein microparticles filled with cellulase to enzymatically degrade nanocellulose for cell growth.","authors":"Céline Bastard, Jann Carl-Theodor Schulte, Md Asaduzzaman, Calvin Hohn, Yonca Kittel, Laura De Laporte, Ronald Gebhardt","doi":"10.1039/d4bm01508h","DOIUrl":"https://doi.org/10.1039/d4bm01508h","url":null,"abstract":"<p><p>For tissue engineering, nanocellulose-based three-dimensional hydrogel structures hold potential as biocompatible support materials for biomimetic scaffolds to regenerate damaged tissues. One challenge of this material is that nanocellulose does not degrade in the human body. Therefore, different carriers are needed to locally deliver cellulase in a controlled manner to degrade the scaffold at the same time the cells grow and proliferate. To achieve this, we developed casein microparticles (CMPs) as delivery vehicles as they are non-toxic and have high porosity with a stable structure at physiological pH values. The porosity of the CMPs was first tested by diffusion experiments with fluorescently labelled dextrans of different sizes as model molecules, demonstrating inward diffusion of dextrans up to 500 kDa. The CMPs continuously release active cellulase, resulting in the degradation of the nanocellulose hydrogel over a time of 21 days, supporting 3D cell growth.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pavel Seredin, Dmitry Goloshchapov, Yaroslav Peshkov, Andrey Potapov, Yana Gribanova, Khidmet Shikhaliev, Yury Ippolitov, Raul O Freitas, Iman A Mahdy, Manal A Mahdy, Boknam Chae
{"title":"Biomimetic organomineral layers with antibacterial properties based on di/tetrahydroquinolinediol and nanocrystalline hydroxyapatite deposited on enamel surface.","authors":"Pavel Seredin, Dmitry Goloshchapov, Yaroslav Peshkov, Andrey Potapov, Yana Gribanova, Khidmet Shikhaliev, Yury Ippolitov, Raul O Freitas, Iman A Mahdy, Manal A Mahdy, Boknam Chae","doi":"10.1039/d5bm00070j","DOIUrl":"https://doi.org/10.1039/d5bm00070j","url":null,"abstract":"<p><p>The paper proposes a strategy for the accelerated deposition of biomimetic organomineral layers on the surface of dental enamel, utilizing di/tetrahydroquinolinediol (hydroxyquinoline) polymerized in the presence of nanocrystalline hydroxyapatite (nano-cHAp). The mechanisms underlying the formation of dental coatings were elucidated through a combination of structural, microstructural, and spectroscopic analytical methods, including synchrotron infrared nanoimaging. Additionally, the antimicrobial effects of these coatings were investigated. It has been demonstrated that the deposition of an organomineral layer, based on polymerized dihydroxyquinoline, on the surface of natural enamel leads to the agglomeration and orientation of hydroxyapatite nanocrystals within the coating. This process enables the layer to replicate the mechanical properties of natural enamel, resulting in a microhardness value that closely resembles that of natural enamel. Using synchrotron s-SNOM, it has been established that the biomimetic organomineral layer possesses the morphological structure of a poly(2,2,4-trimethyl-1,2-dihydroquinoline-6,7-diol (TMDHQ))/nano-cHAp composite film, which is homogeneously distributed and tightly packed on the enamel surface. Furthermore, it has been demonstrated that the dental coating formed from polydihydroxyquinoline and nanocrystalline hydroxyapatite exhibits inhibitory activity against colonies of <i>Streptococcus</i> spp. The developed technology for the formation of dental biomimetic layers, which exhibit simultaneous antibacterial and mineralizing effects, holds significant potential for future clinical applications.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peng Hua, Suleixin Yang, Lin Yu, Yongzhuo Huang, Meiwan Chen
{"title":"Natural product-integrated microneedle patch for rheumatoid arthritis treatment through anti-inflammation and angiogenesis suppression.","authors":"Peng Hua, Suleixin Yang, Lin Yu, Yongzhuo Huang, Meiwan Chen","doi":"10.1039/d5bm00036j","DOIUrl":"https://doi.org/10.1039/d5bm00036j","url":null,"abstract":"<p><p>Synovitis and angiogenesis are two essential pathological factors that synergistically aggravate rheumatoid arthritis (RA), in which the highly inflammatory environment promotes new blood vessel formation while constant angiogenesis renders recruitment of more inflammatory macrophages. Herein, we developed a micelle-embedded dissolvable microneedle to realize both anti-inflammation and anti-angiogenesis effects for enhanced anti-arthritis therapy. Anti-arthritis natural products, berberine (Ber) and sinomenine (Sin), were encapsulated in the reactive oxygen species (ROS)-responsive micelles (B/S-TMs) and self-assembled using thioketal-modified amphiphilic copolymer PLGA-TK-PEG, followed by their integration into a carboxymethyl cellulose-based microneedle to achieve effective transdermal delivery and rapid cargo release. B/S-TMs were accumulated in the RA joint <i>via</i> passive targeting, and they released Ber and Sin through thioketal bond cleavage under a high ROS level environment. Interestingly, Ber or Sin individually exerted anti-inflammatory effect <i>via</i> simultaneously promoting M2 macrophage polarization and anti-angiogenesis effect by decreasing the endothelial cell migration and tube formation. The combined Ber and Sin further amplified these effects. The therapeutic microneedle patch (B/S-TM@MN) significantly decreased the expression of CD68-positive macrophages and CD31-stained blood vessel, attaining improved anti-arthritis efficacy compared with monotherapies in the collagen-induced arthritis (CIA) mouse model. Our work represents a promising strategy for targeting multiple pathological factors for enhanced anti-RA therapy.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gayathri R Ediriweera, Mengdie Li, Nicholas L Fletcher, Zachary H Houston, Muneer Ahamed, Idriss Blakey, Kristofer J Thurecht
{"title":"Harnessing nanoparticles and bioorthogonal chemistries for improving precision of nuclear medicine.","authors":"Gayathri R Ediriweera, Mengdie Li, Nicholas L Fletcher, Zachary H Houston, Muneer Ahamed, Idriss Blakey, Kristofer J Thurecht","doi":"10.1039/d4bm01387e","DOIUrl":"https://doi.org/10.1039/d4bm01387e","url":null,"abstract":"<p><p>The convergence of nanotechnology, radiopharmaceutical development and molecular imaging has unveiled exciting opportunities for the progress of innovative diagnostic and therapeutic strategies, paving the way for significant advancements in biomedical research, especially in relation to cancer. For example, the use of highly sensitive and quantitative nuclear imaging techniques including PET and SPECT, together with nanoparticles for tumour imaging and therapy has recently expanded rapidly. While the long circulating properties of many nanomaterials are beneficial for prodrug chemotherapy formulations, due to the constant decay processes involved in nuclear medicines, directly labelled materials result in prolonged systemic radiation exposure and reduced therapeutic indices due to the unfavourable target-to-background ratios. This is due to the tendency for long circulating nanomaterials to distribute within the blood to other organs, such as the liver and spleen. The recent integration of bioorthogonal chemistry with nanotechnology and molecular imaging/radiotherapy has revolutionized the field by allowing the decoupling of the targeting molecule (<i>i.e.</i> nanomaterial with a bioorthogonal tag) and the imaging/therapeutic radioisotope. In this way, the detection/therapeutic element can be administered as a secondary \"chase\" molecule that contains the bioorthogonal partner, thereby creating an avenue to improve therapeutic index and provide imaging and treatments with reduced risk. This review will provide an overview of the progress made thus far in the field of nuclear imaging and radiotherapy for cancer using the combination of nanomaterials and bioorthogonal chemistry. We also provide a critical evaluation of the challenges and opportunities for using these approaches to better understand disease and treatment mechanisms, with the potential for downstream clinical translation.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiao Zhang, Bowen Zhao, Shiwei Fu, Ronald S Seruya, Hannah E Fanos, Ashley A Petrisor, Yilin Liu, Zixin Yang, Fuwu Zhang
{"title":"Controlling stimulus sensitivity by tailoring nanoparticle core hydrophobicity.","authors":"Xiao Zhang, Bowen Zhao, Shiwei Fu, Ronald S Seruya, Hannah E Fanos, Ashley A Petrisor, Yilin Liu, Zixin Yang, Fuwu Zhang","doi":"10.1039/d5bm00163c","DOIUrl":"https://doi.org/10.1039/d5bm00163c","url":null,"abstract":"<p><p>Cancer remains a significant global health challenge, necessitating the development of more effective therapeutic strategies. This work presents a novel glutathione (GSH)-responsive platform designed to enhance the delivery and efficacy of the anticancer drug mertansine (DM1) through the modulation of pendant groups in polycarbonate-drug conjugates. By systematically varying the hydrophobicity of the pendant groups, we investigated their effects on nanostructures, GSH sensitivity, colloidal stability, drug release profiles, and the <i>in vitro</i> anticancer efficacy of these polymeric nanoparticles, revealing that more hydrophobic pendant groups effectively reduce GSH accessibility for the nanoparticle cores, improve colloidal stability, and slow drug release rates. The results underscore the critical importance of polymer structures in optimizing drug delivery systems and offer valuable insights for future research on advanced nanomaterials with enhanced drug delivery for cancer therapies.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicoletta Inverardi, Maria F Serafim, Amita Sekar, Keita Fujino, Matheus Ferreira, Anthony Marzouca, Emma Nagler, Orhun K Muratoglu, Ebru Oral
{"title":"Wear-resistant antibacterial UHMWPE-based implant materials obtained by radiation crosslinking.","authors":"Nicoletta Inverardi, Maria F Serafim, Amita Sekar, Keita Fujino, Matheus Ferreira, Anthony Marzouca, Emma Nagler, Orhun K Muratoglu, Ebru Oral","doi":"10.1039/d4bm01663g","DOIUrl":"https://doi.org/10.1039/d4bm01663g","url":null,"abstract":"<p><p>The crosslinking of ultrahigh molecular weight polyethylenes (UHMWPEs) by irradiation has been employed for decades to enhance the wear resistance of these materials when used as a load-bearing implant component for joint arthroplasty. This surgical procedure can restore the mobility of patients affected by severe arthritis by the implantation of an artificial joint made of an articulating pair and a bearing component. While the surgery is usually successful, one of the most severe complications is peri-prosthetic joint infection (PJI), which can be extremely difficult to treat and eradicate. The use of UHMWPEs as a platform for the local delivery of antibiotics in addition to their structural function could be extremely beneficial for the improvement in the outcome of PJIs. In this study, we investigated whether irradiation can be used to sterilize and crosslink antibiotic-loaded UHMWPEs, and its effect on the drug eluting and antibacterial properties of these materials. We found that the antibiotics gentamicin sulfate and vancomycin hydrochloride were stable in irradiated UHMWPEs and did not hinder crosslinking of the UHMWPE matrix. Effective crosslinking led to optimal wear resistance, which was comparable to that of clinically available UHMWPEs. Sustained drug release was observed for an extended duration (up to six months) and both the drug eluents and eluted material surfaces showed antibacterial activity against <i>Staphylococcus aureus</i>, the most common causative bacterium for PJIs.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xingan Qiu, Feng Xiang, Hong Liu, Fangbiao Zhan, Xuezhe Liu, Pengzhen Bu, Bikun Zhou, Qiaojian Duan, Ming Ji, Qian Feng
{"title":"Electrical hydrogel: electrophysiological-based strategy for wound healing.","authors":"Xingan Qiu, Feng Xiang, Hong Liu, Fangbiao Zhan, Xuezhe Liu, Pengzhen Bu, Bikun Zhou, Qiaojian Duan, Ming Ji, Qian Feng","doi":"10.1039/d4bm01734j","DOIUrl":"https://doi.org/10.1039/d4bm01734j","url":null,"abstract":"<p><p>Wound healing remains a significant challenge in clinical practice, driving ongoing exploration of innovative therapeutic approaches. In recent years, electrophysiological-based wound healing strategies have gained considerable attention. Specifically, electrical hydrogels combine the synergistic effects of electrical stimulation and hydrogel properties, offering a range of functional benefits for wound healing, including antibacterial activity, real-time wound monitoring, controlled drug release, and electrical treatment. Despite significant progress made in electrical hydrogel research for wound healing, there is a lack of comprehensive, systematic reviews summarizing this field. In this review, we survey the latest advancements in electrical hydrogel technology. After analyzing the mechanisms of electrical stimulation in promoting wound healing, we establish a novel classification framework for electrical hydrogels based on their operational principles. The review further provides an in-depth evaluation of the therapeutic efficacy of these hydrogels in various types of wounds. Finally, we propose future directions and challenges for the development of electrical hydrogels for wound healing.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Acid responsive molybdenum (Mo)-based nanoparticles inhibit the cGAS-STING signaling pathway for sepsis therapy.","authors":"Xinyu Wang, Qingbin He, Lining Wang, Chengzhilin Li, Wenyu Zhang, Zhonghou Rong, Qingqing Yin, Yingchun Zhao","doi":"10.1039/d5bm00007f","DOIUrl":"https://doi.org/10.1039/d5bm00007f","url":null,"abstract":"<p><p>Sepsis, an inflammatory disease caused by bacterial infection, has become a global public health crisis. Excessive reactive oxygen species (ROS) in sepsis patients act as the primary trigger for activating intracellular immune pathways, ultimately leading to multiple organ dysfunction syndrome. The overexpression of acidic metabolites and ROS, characteristic of the infected microenvironment, significantly impedes sepsis treatment. Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, plays a key role in inflammatory diseases. The detrimental effects of STING in sepsis have been well documented. Here, we developed a pH-responsive nanotherapy platform (DMSNM@C-178/PAA) that combines ROS scavenging with cGAS-STING pathway inhibition for anti-inflammatory therapy. This nanoparticle is selectively released in the infected microenvironment, where reduced molybdenum-based polyoxometalates (Mo-POM) efficiently neutralize toxic ROS <i>in vivo</i>, while C-178 selectively inhibits the cGAS-STING pathway, thereby attenuating the inflammatory response and preventing organ deterioration. <i>In vitro</i> and <i>in vivo</i> studies demonstrate that DMSNM@C-178/PAA treats sepsis by eliminating excess ROS and modulating autoimmune dysfunction <i>via</i> the cGAS-STING pathway, providing a novel therapeutic strategy for sepsis management.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}