Hue Vu, Evelien Peeters, Kenneth Hofkens, Katrien Vandemeulebroecke, Sara T'Sas, Charlotte Martin, Steven Ballet, Richard Hoogenboom, Steven Goossens, Tim Lammens, Maaike Van Trimpont, Annemieke Madder
{"title":"Peptide hydrogels as slow-release formulations of protein therapeutics: case study of asparaginase-loaded hydrogels.","authors":"Hue Vu, Evelien Peeters, Kenneth Hofkens, Katrien Vandemeulebroecke, Sara T'Sas, Charlotte Martin, Steven Ballet, Richard Hoogenboom, Steven Goossens, Tim Lammens, Maaike Van Trimpont, Annemieke Madder","doi":"10.1039/d5bm00138b","DOIUrl":"https://doi.org/10.1039/d5bm00138b","url":null,"abstract":"<p><p>In this study, hexamer peptide-based hydrogels were loaded with different model protein cargos and the release profiles investigated to explore the balance between injectability and loading capacity permitting the release of a therapeutically relevant dose. We demonstrate that the release of protein cargos from our hexamer peptide hydrogels depends on the stability of the hydrogel network, the mobility of the cargo to diffuse out of the network, and the interaction between the hydrogel network and the cargo. For the first time, our peptide hydrogels were used to develop an injectable sustained release formulation of a therapeutic enzyme, namely Erwinase®, an FDA-approved asparaginase for the treatment of acute lymphoblastic leukemia. We show that the current hexamer peptide-based hydrogels allow sufficient protein loading and sustained release of the fully active asparaginase enzyme both <i>in vitro</i> and <i>in vivo</i>. Altogether, this study describes how peptide hydrogels can be exploited to provide injectable slow-release formulations of biologics, including enzyme therapeutics, to enhance their clinical applicability.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309317","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}
Kianna Nguyen, Quang Tuan Che, Quoc Huynh Nguyen, Kihak Gwon, Alan Gonzalez Suarez, Gulnaz Stybayeva, Robert Huebert, Quinn Peterson, Alexander Revzin
{"title":"Microencapsulation of pluripotent stem cell-derived pancreatic and liver cells: biological needs and technological solutions.","authors":"Kianna Nguyen, Quang Tuan Che, Quoc Huynh Nguyen, Kihak Gwon, Alan Gonzalez Suarez, Gulnaz Stybayeva, Robert Huebert, Quinn Peterson, Alexander Revzin","doi":"10.1039/d5bm00696a","DOIUrl":"https://doi.org/10.1039/d5bm00696a","url":null,"abstract":"<p><p>Pluripotent stem cell-derived products are versatile tools for studying disease and developing cellular therapies. Microencapsulation technologies offer solutions for scalability, prolonged survival, and transplantability of these stem-cell derived products. This review describes current methods and materials utilized for stem cell encapsulation. Specifically, the differentiation of stem cell-derived β cells and hepatocytes is explored. This includes the current state of differentiation protocols, examples of microencapsulation for differentiation and transplantation, and future directions.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309316","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":"Osteoinductive IL-8/tDM/PLGA scaffolds based on autologous BMSC recruitment and endogenous growth factor regulation.","authors":"Zihao Zhao, Mengjie Xu, Zhou Zhang, Xing Yin, Ximing Pu, Juan Wang, Xiaoming Liao, Zhongbing Huang, Shunze Cao, Guangfu Yin","doi":"10.1039/d5bm00469a","DOIUrl":"https://doi.org/10.1039/d5bm00469a","url":null,"abstract":"<p><p>The <i>in vitro</i> expanded seed cells and the supraphysiological doses of exogenous growth factors both pose huge safety risks in bone regeneration. In this study, a novel IL-8/tDM/PLGA composite scaffold was developed, where chemokine interleukin-8 (IL-8) and transferable decellularized matrix (tDM) were uniformly overlaid on exterior and interior surfaces of poly(lactic-<i>co</i>-glycolic acid) (PLGA) porous substrates. The <i>in vitro</i> experiments confirmed that the synergy of tDM and IL-8 achieved the obvious promotion of osteogenesis and angiogenesis <i>via</i> enhancing chemotaxis, adhesion, spreading, osteogenic differentiation and mineralization of bone marrow mesenchymal stem cells (BMSCs). IL-8 mediated the <i>in situ</i> recruitment of BMSCs and macrophages <i>via</i> binding with C-X-C motif chemokine receptor 2 (CXCR2), while maintaining cellular viability without inducing macrophage polarization. Moreover, tDM improved BMSC adhesion and spreading <i>via</i> the recognition and binding of the affinitive ligand existing in tDM by the cell adhesion molecules (CAMs) on the BMSC cytomembrane. Furthermore, tDM promoted the osteogenic differentiation and mineralization of BMSCs, benefiting from the retained growth factors. In a rat femoral defect model, the IL-8/tDM/PLGA scaffold significantly accelerated new bone mineralization and maturation through synergistic regulations of cell recruitment, matrix adhesion, and osteogenic signaling pathways. After 8 weeks post-implantation of the IL-8/tDM/PLGA scaffolds, the bone volume fraction of the newly formed bone, trabecular number, and trabecular separation at the defect site were 47%, 1.21 mm<sup>-2</sup>, and 0.50 mm, respectively, which presented significantly better bone repair effects than those in other groups. These results demonstrated that the innovative bone regeneration strategy combining chemokine-driven recruitment and endogenous tDM regulation offered a potential solution for clinical repair of large-sized bone defects.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300716","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":"Self-targeted liposomes for enhancing chemotherapeutic efficacy of pancreatic cancer by degrading the extracellular matrix and eradicating intra-tumoral bacteria.","authors":"Siyu Zhang, Da-Yuan Wang, Jing Li, Xiaohui Wu, Qinghao Huo, Shuoshuo Song, Xiao-Han Tian, Feihe Ma, Jing Shen, Linqi Shi","doi":"10.1039/d5bm00786k","DOIUrl":"https://doi.org/10.1039/d5bm00786k","url":null,"abstract":"<p><p>Pancreatic cancer is one of the lethal malignancies resulting from the dense extracellular matrix (ECM) hindering the diffusion of cancer-chemotherapeutics and the intra-tumoral bacteria promoting tumor growth and inactivating cancer-chemotherapeutics, causing poor treatment prognoses. It is difficult to exert efficacy spatiotemporally by combined administration of chemotherapeutics, ECM degradation agents and antibiotics, and this may disturb the microflora in critically ill patients. To establish intra-tumor co-delivery of cancer-chemotherapeutics, ECM degradation agents and antibiotics, self-targeting DCPA (2-(4-((1,5-bis(octadecyloxy)-1,5-dioxopentan-2-yl)carbamoyl)pyridin-1-ium-1-yl)acetate) liposomes with complexed water as pH responsive functionality were self-assembled and PEGylated ciprofloxacin was used as a lipid-membrane component, together with bromelain and gemcitabine loaded in-core (B/G-C/DCPA-H<sub>2</sub>O). These triple-loaded liposomes were stealthily transported in the blood circulation to accumulate in the acidic environment of the tumor site. Upon tumor self-targeting, DCPA-H<sub>2</sub>O and PEGylated ciprofloxacin became protonated, disturbing the balance in the lipid membrane to cause liposome burst and simultaneous release of bromelain, PEGylated ciprofloxacin and gemcitabine. Treatment of mice with these self-targeting liposomes yielded significantly higher responses in <i>Escherichia coli</i> infected pancreatic cancer with respect to both infection and tumor volume than the administration of bromelain, gemcitabine and gemcitabine loaded C/DCPA-H<sub>2</sub>O liposomes alone.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300717","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":"<i>Saponin</i>-mediated cell membrane interference nanomedicine potentiates tumor chemo-immunotherapy <i>via</i> a perforin-granzyme-like mechanism.","authors":"Jingsong Lu, Baoli Ma, Ying Li, Sumei Chen, Muyan Zhang, Zhenhu Guo, Xiaohan Gao, Ufurahi-Pambe Neema, Abdul Fahad, Wensheng Xie, Xiaodan Sun, Xiumei Wang, Guifeng Zhang, Jing Yu, Shenglei Che, Yen Wei, Lingyun Zhao","doi":"10.1039/d5bm00564g","DOIUrl":"https://doi.org/10.1039/d5bm00564g","url":null,"abstract":"<p><p>Pore formation can facilitate the release of various intracellular substances upon cell death, which is of critical benefit in tumor immunotherapy by immunogenic cell death (ICD). Given that effective endogenous antigen release is of primary importance for ICD-eliciting immunogenicity, in addition to enhancing the cytotoxicity of ICD, we designed an immunogenic induction strategy <i>via</i> pore formation based on saponin, a composite medium of membrane-disrupting agents. In this study, saponin/polyphenol (ZS-TA) at appropriate concentrations directly caused membrane perforation by removing cholesterol from the membrane, thereby leading to the release of intracellular substances. Simultaneously, <i>in situ</i> nano-antigens (nano-Ags) were formed through the mechanism of protein-polyphenol interaction, and the nano-Ag served as a reservoir of antigens to trigger long-term immune effects. Meanwhile, this membrane perforation enhanced the uptake of chemotherapeutic drugs, serving as a general approach for drug delivery. Therefore, this work provides insights into the design of enhanced drug delivery systems and <i>in situ</i> vaccines to sensitize tumor chemo-immunotherapy.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281731","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}
Yi Xiang, Yazhi Sun, Jiaao Guan, Tobias Meng-Saccoccio, Ting-Yu Lu, David Berry, Shaochen Chen
{"title":"Iohexol as a refractive index tuning agent for bioinks in high cell density bioprinting.","authors":"Yi Xiang, Yazhi Sun, Jiaao Guan, Tobias Meng-Saccoccio, Ting-Yu Lu, David Berry, Shaochen Chen","doi":"10.1039/d5bm00585j","DOIUrl":"https://doi.org/10.1039/d5bm00585j","url":null,"abstract":"<p><p>Light-based 3D bioprinting has emerged as a transformative technology for fabrication of biomimetic tissues and artificial organs. High cell density (HCD) bioprinting aims to recapitulate the cellular density and interactions in native tissue, but faces significant challenges in achieving both high resolution and structural fidelity due to light scattering during the photopolymerization process. Refractive index (RI) tuning of the bioink mitigates light scattering to improve printing fidelity. In this study, we developed an iohexol (IHX)-based bioink for digital light processing (DLP) bioprinting. IHX effectively tuned the RI of the bioink to match cellular components to reduce light scattering while still maintaining printability. The bioink demonstrated excellent biocompatibility across multiple cell types, including epithelial, endothelial, parenchymal, and stem cells, while simultaneously supporting post-printing cellular viability, reorganization, and functionality. Using IHX-bioink, we fabricated tubular constructs with lumen diameters ranging from 400 μm to 1.1 mm and utilized strategies to minimize overpolymerization and ensure lumen fidelity. Our results underscore IHX-bioink as a promising biomaterial for scalable, RI-matching 3D bioprinting, enabling the creation of perfusable, HCD constructs for various applications in tissue engineering and regenerative medicine.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281732","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}
Rui Zhang, Mingxing Liu, Hongjin Li, Yan Huang, Coo Yee Nah, Chi Yao, Dayong Yang
{"title":"Bioactive DNA hydrogel interfacing with living cells and extracellular vesicles.","authors":"Rui Zhang, Mingxing Liu, Hongjin Li, Yan Huang, Coo Yee Nah, Chi Yao, Dayong Yang","doi":"10.1039/d5bm00690b","DOIUrl":"https://doi.org/10.1039/d5bm00690b","url":null,"abstract":"<p><p>Biological vesicles, such as living cells and extracellular vesicles (EVs) in biological systems, are important agents and regulators of life functions and play an irreplaceable role in physiological processes and disease progression. The maintenance of high bioactivity and structural integrity as well as selective isolation of target biological vesicles from complex biological systems are of great significance for downstream applications, such as early diagnosis, treatment and prognostic monitoring of major diseases. Bioactive hydrogel is a material made of hydrogel containing bioactive molecules that simulate living systems <i>in vitro</i>. By exploiting the unique molecular recognition and sequence programmability of deoxyribonucleic acid (DNA), DNA containing multifunctional modules serves as the material chemistry basis. Through molecular design and functional unit incorporation, these strategies enable the construction of DNA hydrogels capable of targeted vesicle recognition. This review discusses interactions between DNA hydrogels and biological vesicles, focuses on controllable release mechanisms of vesicles, and highlights recent advances in biomedical applications boosted by bioactive DNA hydrogels, including cell and EV isolation, cell engineering and three-dimensional (3D) culture, disease detection, and disease treatments. First, the interaction and controllable release mechanisms of bioactive DNA hydrogels are summarized, and relevant research based on these mechanisms is reviewed. Second, pioneering work in biomaterial applications is summarized. Finally, it is concluded with the challenges faced by DNA hydrogels and the future prospects of bioactive DNA hydrogels.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264889","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":"Cytosolic protein delivery <i>via</i> protein-bound microparticles based on anionic boron clusters and cationic polymers.","authors":"Yuya Hirai, Yoshimasa Makita, Makoto Nakagawa, Rie Kakehashi, Shin-Ichi Fujiwara","doi":"10.1039/d5bm00346f","DOIUrl":"https://doi.org/10.1039/d5bm00346f","url":null,"abstract":"<p><p>Direct protein delivery to the cytosol facilitates immediate functional expression of proteins without the risks associated with gene introduction. However, the technology for delivering various proteins to the cytosol is still in its infancy. Herein, the formation of microparticles comprising anionic boron clusters and the cationic polymer hexadimethrine bromide (HDB) is demonstrated. In particular, the microparticles formed from dodecabromododecaborate clusters and HDB are confirmed to be bound with proteins. The protein-bound boron cluster/polymer-based microparticles (protein·BPMs) are internalized into cells <i>via</i> endocytosis. Upon internalization, the protein·BPMs release the proteins with different isoelectric points and sizes into the cytosol. Furthermore, an enzyme is delivered by protein·BPMs into the cytosol of various cell types while maintaining its functional activity. This method, owing to the simple preparation of protein·BPMs, represents a promising approach for delivering diverse proteins to various cell types. Our findings open new avenues for utilizing boron clusters in cytosolic delivery systems.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256846","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}
Manjyot Kaur Chug, Gabrielle Aluisio, Cole Bousquet, Mark Garren, Yun Qian, Joseph H Campbell, Elizabeth J Brisbois
{"title":"Enhancing hand hygiene compliance through the long-lasting antimicrobial effects of nitric oxide-releasing hand sanitizer gel.","authors":"Manjyot Kaur Chug, Gabrielle Aluisio, Cole Bousquet, Mark Garren, Yun Qian, Joseph H Campbell, Elizabeth J Brisbois","doi":"10.1039/d5bm00359h","DOIUrl":"10.1039/d5bm00359h","url":null,"abstract":"<p><p>Effective hand hygiene is crucial for reducing the transmission of disease-causing pathogens. While alcohol-based hand sanitizers have become popular, their increased usage during the COVID-19 pandemic raised concerns about their short-lived activity and potential side effects. The increased application of hand sanitizers and harmful side effects has necessitated an effective alternative with prolonged and enhanced antimicrobial properties which could result in a reduced number of sanitizer applications. To address these issues and improve antimicrobial efficacy, this study developed a nitric oxide (NO)-releasing hand sanitizer (NORel) gel enriched with other antimicrobial and moisturizing ingredients like ethanol, tea tree oil, and glycerin. The NORel gel underwent comprehensive analysis, including assessments of pH for 60 d, rheology, NO release, cytocompatibility, and <i>in vitro</i> and <i>ex vivo</i> antimicrobial effectiveness on rabbit skin proving its ability to eliminate over 97% of bacteria and fungi, including antibiotic-resistant strains. One NORel gel formulation, NORel2, demonstrated antimicrobial activity comparable to a commercial alcohol-based gel containing 62% ethyl alcohol, achieving a reduction of more than 5 logs in <i>S. aureus</i> bacteria on a rabbit skin model. Additionally, the NORel gel significantly outperformed the commercial alcohol gel by maintaining its antimicrobial efficacy on infected rabbit skin, showing a persistent activity with a 1.6-log reduction in viable <i>S. aureus</i> 2 h after application. This research introduces a biocompatible NO-releasing gel with superior antimicrobial properties compared to common alcohol-based sanitizers, making it an effective hand hygiene solution to reduce infections, especially in high-risk environments.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of rapamycin-loaded PLGA nanoparticles for treating retinopathy of prematurity.","authors":"Hui Shi, Yuqiao Ju, Qing Chang, Lian Cen","doi":"10.1039/d5bm00555h","DOIUrl":"https://doi.org/10.1039/d5bm00555h","url":null,"abstract":"<p><p>With the increasing incidence of retinopathy of prematurity (ROP) and the gradual emergence of side effects associated with existing treatments, the development of novel nano-therapy strategies for ROP has become critically urgent. The aim of the current study was to explore the possibility of developing PLGA nanoparticles loaded with rapamycin (RPM) (RPM-PLGA NPs) for the sustained release of RPM as a nano-therapy for ROP intervention. RPM-PLGA NPs were prepared using a nanoprecipitation method, and their physicochemical properties were characterized. The safety profile and therapeutic efficacy of RPM-PLGA NPs were evaluated in BV2, HUVEC cells and in an oxygen-induced retinopathy (OIR) mouse model. RPM-PLGA NPs of 144.23 ± 3.40 nm, a polydispersity index of 0.05 ± 0.02, an encapsulation efficiency of 81.39%, and a drug loading capacity of 16.28% were successfully prepared. The sustained and gradual release of RPM from these NPs was achieved for over 35 days. It was demonstrated that RPM-PLGA NPs had no significant effect on the viability and migration of BV2 and HUVECs. In the oxygen-induced OIR model, RPM-PLGA NPs significantly reduced the areas of vaso-obliteration and pathological neovascularization in the mouse retina, showing superior therapeutic effects compared to RPM alone. These findings validated the feasibility of RPM-PLGA NPs as an intravitreal injection for the treatment of ROP. It is believed that the current study could provide promising experimental data for nano-therapy as an effective and superior treatment for ROP with few side effects.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256847","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}