Biomaterials Science最新文献

{"title":"Modulation of biomaterial-induced foreign body response by regulating the differentiation and migration of Treg cells through the CXCL12–CXCR4/7 axis†","authors":"Siyi Yu, Yuan You, Lan Liu, Xinjie Cai and Cui Huang","doi":"10.1039/D4BM01474J","DOIUrl":"10.1039/D4BM01474J","url":null,"abstract":"<p >Tissue exposure to implanted biomaterials triggers a foreign body response (FBR), which is a stepwise immunological process involving innate immune cells and tissue repair cells. Although the regulatory T (Treg) cells play a crucial role in inflammation and tissue repair, their function in the process of FBR has not been well investigated. In this study, as titanium (Ti) exhibits better biocompatibility and induces milder FBR than polymethyl methacrylate (PMMA), we analyzed the characteristics of Treg cells during FBR caused by the two types of biomaterials. In a rat femur implantation model, we found that the number of Treg cells around titanium implants was much more than that in the PMMA-implanted group. Meanwhile, the expression of CXCR4 in tissues around Ti implants was significantly higher, and the expression of CXCR7 was lower. When co-cultured with biomaterials and macrophages, the differentiation and migration of Treg cells in the Ti-implanted group were promoted, and this effect could be modulated by CXCR4/7 inhibitors. Moreover, targeting CXCR4/7 influenced the amount of Treg cells <em>in vivo</em> and then reversed the FBR induced by PMMA or Ti implants. In summary, our findings revealed the role of CXCR4/CXCR7 in regulating the migration and differentiation of Treg cells during FBR and suggested that the CXCL12–CXCR4/CXCR7 axis may serve as a potential therapeutic target for immunomodulating foreign body response.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 6","pages":" 1529-1542"},"PeriodicalIF":5.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389528","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":"Research progress of metal–CpG composite nanoadjuvants in tumor immunotherapy","authors":"Yifan Chen, Danna Feng, Yilin Cheng, Xianmeng Jiang, Lin Qiu, Li Zhang, Dongjian Shi and Jianhao Wang","doi":"10.1039/D4BM01399A","DOIUrl":"10.1039/D4BM01399A","url":null,"abstract":"<p >The practical benefits and therapeutic potential of tumor vaccines in immunotherapy have drawn significant attention in the field of cancer treatment. Among the available vaccines, nanovaccines that utilize nanoparticles as carriers or adjuvants have demonstrated considerable effectiveness in combating cancer. Cytosine–phosphate–guanine oligodeoxynucleotide (CpG ODN), a common adjuvant in tumor nanovaccines, activates both humoral and cellular immunity by recognizing toll-like receptor 9 (TLR9), thereby aiding in the prevention and treatment of cancer. Metal nanoparticles hold great promise in tumor immunotherapy due to their adjustable size, surface functionalization, ability to regulate innate immunity, and capacity for controlled delivery of antigens or immunomodulators. Consequently, composite nanoadjuvants, formed by combining metal nanoparticles with CpG ODNs, can be customized to meet the specific performance requirements of different application scenarios, effectively overcoming the limitations of conventional immunotherapy approaches. This review provides a comprehensive analysis of the critical role of metal–CpG composite nanoadjuvants in advancing vaccine adjuvants for cancer therapy and prevention, highlighting their efficacy in preclinical settings.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 7","pages":" 1605-1623"},"PeriodicalIF":5.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490094","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":"In vitro and in vivo degradation studies of a dual medical-grade scaffold design for guided soft tissue regeneration†","authors":"Mina Mohseni, Silvia Cometta, Leopold Klein, Marie-Luise Wille, Cedryck Vaquette, Dietmar W. Hutmacher and Flavia Medeiros Savi","doi":"10.1039/D4BM01132E","DOIUrl":"10.1039/D4BM01132E","url":null,"abstract":"<p >Biodegradable scaffolds with tailored mechanical and structural properties are essential for scaffold-guided soft tissue regeneration (SGSTR). SGSTR requires scaffolds with controllable degradation and erosion characteristics to maintain mechanical and structural integrity and strength for at least four to six months. Additionally, these scaffolds must allow for porosity expansion to create space for the growing tissue and exhibit increased mechanical compliance to match the properties of the newly formed tissue. Although progress has been made in this area, previous studies have yet to fully explore these aspects using biodegradable polymers that are synthesized and 3D printed into filaments classified as medical-grade. In this study, we optimized scaffold design based on the properties of biodegradable materials and employed digital-assisted 3D printing to adjust the degradation pathway of dual-material scaffolds dynamically, thereby modulating mechanical and structural changes. Two medical-grade 3D printing filaments were utilized: Dioxaprene® (DIO), which has a degradation rate of approximately six months, and Caproprene™ (CAP), which has a degradation rate of about 36 months. The scaffolds were 3D printed with these materials to create the desired architecture. An <em>in vitro</em> degradation study showed the increasing pore size and compliance (&gt;90% increase) of the scaffold architecture <em>via</em> the breakdown of DIO. Meanwhile, the slow-degrading CAP maintained long-term mechanical and structural integrity. Furthermore, over six months of subcutaneous implantation in rats, the dual material showed an approximately two-fold increase in mechanical compliance and free volume expansion, with the pore size increasing from 1 mm to 2 mm to accommodate the growing tissue. The scaffold remained structurally intact and provided mechanical support for the newly formed tissue. Histological and immunohistochemical analyses indicated good <em>in vivo</em> biocompatibility, tissue guidance, and the formation of organized soft tissue architecture, supported by an extensive network of blood vessels.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 8","pages":" 2115-2133"},"PeriodicalIF":5.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603082","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":"Pentablock thermoresponsive hydrogels for chemotherapeutic delivery in a pancreatic cancer model†","authors":"Amr Elsherbeny, Hulya Bayraktutan, Nurcan Gumus, Phoebe McCrorie, Andres Garcia-Sampedro, Shreeya Parmar, Alison A. Ritchie, Marian Meakin, Umut Can Oz, Ruman Rahman, Jennifer C. Ashworth, Anna M. Grabowska, Cara Moloney and Cameron Alexander","doi":"10.1039/D4BM01629G","DOIUrl":"10.1039/D4BM01629G","url":null,"abstract":"<p >The design of biodegradable and thermoresponsive polymeric hydrogels with tuneable properties holds immense promise for localised and sustained drug delivery. In this study, we designed and synthesised a library of novel pentablock copolymers, incorporating poly(<small>D</small>,<small>L</small>-lactide) (PLA) into methoxypoly(ethylene glycol)-poly(ε-caprolactone)-methoxypoly(ethylene glycol) (mPEG-PCL-mPEG, or PECE) hydrogels to enhance the hydrolytic degradation and drug release profiles. A pentablock copolymer, methoxypoly(ethylene glycol)-<em>b</em>-poly(<small>D</small>,<small>L</small> lactide)-<em>b</em>-poly(ε-caprolactone)-<em>b</em>-poly(<small>D</small>,<small>L</small> lactide)-<em>b</em>-methoxypoly(ethylene glycol) (mPEG-PLA-PCL-PLA-mPEG, or PELCLE), was selected based on its thermoresponsive sol–gel transition behaviour at a physiologically relevant temperature (37 °C). Physicochemical characterisation revealed that both PECE and PELCLE hydrogels self-assembled into micellar structures, with PELCLE exhibiting smaller micellar sizes compared to PECE. The incorporation of PLA led to reduced hydrogel stiffness, enhanced degradability, and decreased swelling compared to PECE. <em>In vitro</em> drug release studies demonstrated that both hydrogels exhibited sustained release of various anti-cancer drugs, with PELCLE generally showing slower release kinetics, highlighting its potential for prolonged drug delivery. For potential pancreatic cancer applications, we evaluated the biocompatibility and therapeutic efficacy of PELCLE hydrogels loaded with gemcitabine and oxaliplatin (GEMOX). <em>In vitro</em> and <em>in vivo</em> studies demonstrated safety and some anti-tumour efficacy of GEMOX-loaded PELCLE compared to free drug administration, attributed to enhanced tumour retention and sustained drug release. These findings highlight the potential of the PELCLE hydrogel as a versatile and effective local drug delivery platform for the treatment of pancreatic cancer and other solid tumours, warranting further investigation towards its clinical translation.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 7","pages":" 1831-1848"},"PeriodicalIF":5.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/bm/d4bm01629g?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497450","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":"Influence of lung extracellular matrix from non-IPF and IPF donors on primary human lung fibroblast biology†","authors":"Mohammadhossein Dabaghi, Ryan Singer, Alex Noble, Aidee Veronica Arizpe Tafoya, David A. González-Martínez, Tamaghna Gupta, Cécile Formosa-Dague, Ivan O. Rosas, Martin R. Kolb, Yaron Shargall, Jose M. Moran-Mirabal and Jeremy A. Hirota","doi":"10.1039/D4BM00906A","DOIUrl":"10.1039/D4BM00906A","url":null,"abstract":"<p >Fibrosis, a pathological hallmark of various chronic diseases, involves the excessive accumulation of extracellular matrix (ECM) components leading to tissue scarring and functional impairment. Understanding how cells interact with the ECM in fibrotic diseases such as idiopathic pulmonary fibrosis (IPF), is crucial for developing effective therapeutic strategies. This study explores the effects of decellularized extracellular matrix (dECM) coatings derived from non-IPF and IPF donor lung tissue samples on the behavior of primary human lung fibroblasts (HLFs). Utilizing a substrate coating method that preserves the diversity of <em>in situ</em> ECM, we studied both the concentration-dependent effects and the intrinsic biochemical cues of ECM on cell morphology, protein expression, mechanobiology biomarkers, and gene expression. Morphological analysis revealed that HLFs displayed altered spreading, shape, and nuclear characteristics in response to dECM coatings relative to control plastic, indicating a response to the physical and biochemical cues. Protein expression studies showed an upregulation of α-smooth muscle actin (α-SMA) in cells interacting with both non-IPF and IPF dECM coatings, that was more prominent at IPF dECM-coated surface. In addition, YAP localization, a marker of mechanotransduction, was also dysregulated on dECM coatings, reflecting changes in mechanical signaling pathways. Gene expression profiles were differentially regulated by the different dECM coatings. The developed dECM coating strategy in this work facilitates the integration of tissue-specific biochemical cues onto standard cell culture platforms, which is ideal for high-throughput screening. Importantly, it minimizes the requirement for human tissue samples, especially when compared to more sample-intensive 3D models like dECM-based hydrogels.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 7","pages":" 1721-1741"},"PeriodicalIF":5.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/bm/d4bm00906a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447532","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":"Matrix deformation and mechanotransduction as markers of breast cancer cell phenotype alteration at matrix interfaces†","authors":"Cornelia Clemens, Rosa Gehring, Philipp Riedl and Tilo Pompe","doi":"10.1039/D4BM01589D","DOIUrl":"10.1039/D4BM01589D","url":null,"abstract":"<p >The dissemination of metastatic cells from the primary tumor into the surrounding tissue is a key event in the progression of cancer. This process involves the migration of cells across defined tissue interfaces that separate the dense tumor tissue from the adjacent healthy tissue. Prior research showed that cell transmigration across collagen I matrix interfaces induces a switch towards a more aggressive phenotype including a change in directionality of migration and chemosensitivity correlated to increased DNA damage during transmigration. Hence, mechanical forces acting at the nucleus during transmigration are hypothesized to trigger phenotype switching. Here, we present results from a particle image velocimetry (PIV) based live cell analysis of breast cancer cell transmigration across sharp matrix interfaces constituted of two collagen type I networks with different pore sizes. We found strong and highly localized collagen network deformation caused by cellular forces at the moment of crossing interfaces from dense into open matrices. Additionally, an increased contractility of transmigrated cells was determined for cells with the switch phenotype. Moreover, studies on mechanotransductive signaling at the nucleus, emerin translocation and YAP activation, indicated a misregulation of these signals for transmigrated cells with altered phenotype. These findings show that matrix interfaces between networks of different pore sizes mechanically challenge invasive breast cancer cells during transmigration by a strong asymmetry of contracting forces, impeding nuclear mechanotransduction pathways, with a subsequent trigger of more aggressive phenotypes.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 6","pages":" 1578-1589"},"PeriodicalIF":5.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/bm/d4bm01589d?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439417","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":"Branched silver–iron oxide nanoparticles enabling highly effective targeted and localised drug-free thrombolysis","authors":"Karla X. Vazquez-Prada, Shehzahdi S. Moonshi, Yuao Wu, Karlheinz Peter, Xiaowei Wang, Zhi Ping Xu and Hang Thu Ta","doi":"10.1039/D4BM01089B","DOIUrl":"10.1039/D4BM01089B","url":null,"abstract":"<p >Ultrasound has been widely used as an external stimulus to trigger drug release from nanomaterials in thrombosis treatment. Here, we introduce a novel strategy leveraging nanomaterials not for drug delivery, but for enhancing US-induced thrombolysis. This innovative strategy is particularly significant, as thrombolytic drugs inherently pose a risk of systemic bleeding. We combined branched silver–iron oxide nanoparticles (AgIONPs) with low-intensity focused ultrasound to evaluate their thrombolytic potential. Binding assays in in vitro human blood clots and in a thrombosis mouse model confirmed that the targeted AgIONPs specifically bound to thrombi. Upon ultrasound activation, AgIONPs facilitated thrombolysis via two key mechanisms: hyperthermia driven by the nanoparticle-mediated thermal conversion, and mechanical shear forces induced by ultrasound. The combination of AgIONPs and US generated a synergistic thrombolytic effect, demonstrating significant efficacy in both <em>in vitro</em> and <em>in vivo</em>.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 7","pages":" 1683-1696"},"PeriodicalIF":5.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439414","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":"Crosslink strength governs yielding behavior in dynamically crosslinked hydrogels†","authors":"Noah Eckman, Abigail K. Grosskopf, Grace Jiang, Krutarth Kamani, Michelle S. Huang, Brigitte Schmittlein, Sarah C. Heilshorn, Simon Rogers and Eric A. Appel","doi":"10.1039/D4BM01323A","DOIUrl":"10.1039/D4BM01323A","url":null,"abstract":"<p >Yielding of dynamically crosslinked hydrogels, or the transition between a solid-like and liquid-like state, allows facile injection and utility in translational biomedical applications including delivery of therapeutic cells. Unfortunately, the time-varying nature of the transition is not well understood, nor are there design rules for understanding the effects of yielding on encapsulated cells. Here, we unveil underlying molecular mechanisms governing the yielding transition of dynamically crosslinked gels currently being researched for use in cell therapy. We demonstrate through nonlinear rheological characterization that the network dynamics of the dynamic hydrogels dictate the speed and character of their yielding transition. Rheological testing of these materials reveals unexpected elastic strain stiffening during yielding, as well as characterization of the rapidity of the yielding transition. A slower yielding speed explains enhanced protection of directly injected cells from shear forces, highlighting the importance of mechanical characterization of all phases of yield-stress biomaterials.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 6","pages":" 1501-1511"},"PeriodicalIF":5.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/bm/d4bm01323a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254252","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":"Sulfated Undaria pinnatifida polysaccharides inhibit kidney stone formation through crystalline modulation and relieving cellular oxidative damage and inflammation†","authors":"Xue-Wu Chen, Jun Long, Quan Zhang, Ling-Hong Huang and Xin-Yuan Sun","doi":"10.1039/D4BM01362J","DOIUrl":"10.1039/D4BM01362J","url":null,"abstract":"<p > <em>Background</em>: Calcium oxalate (CaOx) crystal deposition and its resultant cellular oxidative damage and inflammation are important causes of renal stone formation. It is clinically important to conduct research on multifunctional anti-stone drugs targeting these predisposing factors. <em>Methods</em>: We modified natural <em>Undaria pinnatifida</em> polysaccharide (UPP0) by sulfation <em>via</em> the sulfur trioxide-pyridine method, resulting in four sulfated polysaccharides with varying sulfate group (–OSO<small>₃</small><small>⁻</small>) contents: 1.59% (UPP0), 6.03% (UPP1), 20.83% (UPP2), and 36.39% (UPP3), and compared their differences in the inhibition of crystalline formation, renal injury, and inflammation in the process of renal stone formation at chemical and cellular levels. <em>Results</em>: The UPPS were able to inhibit the nucleation, growth and aggregation of CaOx crystals <em>in vitro</em>. Among them, UPP3 with the maximum sulfate group content showed the greatest crystallization inhibition ability. The nucleation inhibition and aggregation inhibition of UPP3 at a concentration of 0.5 mg mL<small>⁻¹</small> were as high as 80.21% and 72.34%, respectively. The CaOx crystal size regulated by UPP3 was significantly reduced from 25.9 ± 2.8 μm to 5.9 ± 1.2 μm. Furthermore, UPPS were observed to up-regulate the expression of the antioxidant enzyme superoxide dismutase (SOD) in cells, reduce the levels of ROS and malonaldehyde (MDA), enhance lysosomal integrity, decrease intracellular Ca<small>²⁺</small> levels, inhibit the decline in mitochondrial membrane potential, reduce the production of cellular inflammatory factors (TNF-α, MCP-1, IL-18, and IL-1β), and ultimately inhibit cell apoptosis. <em>Conclusion</em>: UPPS combine multiple biological functions of crystallization regulation, antioxidant and anti-inflammatory, and have important potential in the prevention of kidney stones. Sulfation modification can improve the biological activity of UPP0 and provide a reference for screening and optimization methods of stone drugs.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 6","pages":" 1512-1528"},"PeriodicalIF":5.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381198","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":"Correction: 3D printing of wearable sensors with strong stretchability for myoelectric rehabilitation","authors":"Jianan Zhan, Yueying Kong, Xi Zhou, Haihuan Gong, Qiwei Chen, Xianlin Zhang, Jiankai Zhang, Yilin Wang and Wenhua Huang","doi":"10.1039/D5BM90011E","DOIUrl":"10.1039/D5BM90011E","url":null,"abstract":"<p >Correction for ‘3D printing of wearable sensors with strong stretchability for myoelectric rehabilitation’ by Jianan Zhan <em>et al.</em>, <em>Biomater. Sci.</em>, 2025, https://doi.org/10.1039/d4bm01434k.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 5","pages":" 1354-1354"},"PeriodicalIF":5.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/bm/d5bm90011e?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187835","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}