Tissue Engineering Part A最新文献

{"title":"Induction of M2 Macrophages by Fibrin Hydrogels Enhances Bone Regeneration.","authors":"Ryosuke Aihara, Kazumasa Murata, Tomo Unzai, Chiaki Kitamura, Yasuhiko Tabata","doi":"10.1177/19373341251364271","DOIUrl":"10.1177/19373341251364271","url":null,"abstract":"<p><p>Bone regeneration remains a significant challenge in regenerative medicine. In this context, fibrin hydrogels have attracted attention as a promising biomaterial that regulates the inflammatory response and promotes tissue repair by influencing macrophages. In this study, we investigated the immunomodulatory effects of fibrin hydrogels on macrophage polarization and their subsequent impact on bone regeneration. It is widely recognized that M1 macrophages produce tumor necrosis factor alpha (TNF-α), while M2 macrophages produce interleukin-10 (IL-10). When undifferentiated mouse bone marrow-derived macrophages were stimulated with lipopolysaccharides (LPS), a marked increase in the proinflammatory cytokine TNF-α was observed. However, coculture with fibrin hydrogels in the presence of LPS significantly suppressed TNF-α production while enhancing the secretion of the anti-inflammatory cytokine IL-10. Furthermore, in a rat calvarial defect model, tissue analysis 1-week postimplantation of fibrin hydrogels revealed an upregulation of M2 macrophage markers (CD163, CD204, and CD206), indicating a shift toward an anti-inflammatory phenotype. Notably, 11 weeks after implantation, the fibrin hydrogel-treated sites exhibited enhanced bone regeneration. These findings highlight the potential of fibrin hydrogels as an immunomodulatory biomaterial that facilitates bone repair by promoting M2 macrophage polarization and modulating the local inflammatory microenvironment.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"132-140"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144823285","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":"Pre-Culture of Scaffolds with Vasculogenic Cells Improves Stem Cell-Derived β Cell Transplantation.","authors":"Kelly M Crumley, Elizabeth J Bealer, Nicholas G Schott, Jan P Stegemann, Lonnie D Shea","doi":"10.1177/19373341251398054","DOIUrl":"10.1177/19373341251398054","url":null,"abstract":"<p><p>Transplantation of stem cell-derived β cells is a promising treatment for type-1 diabetes, increasing the supply of insulin-producing cells beyond that of cadaveric islet transplantation. Transplant success is limited by cell death after transplantation, with insufficient oxygen and nutrient accessibility strongly contributing to apoptosis and de-differentiation. Herein, we investigate cotransplantation of endothelial cells and fibroblasts with stem cell-derived β cells to enhance survival and function posttransplantation. A microporous poly (lactide coglycolide) scaffold was used for culture and transplantation of stem cell-derived β cells. Coculture of the stem cell-derived β cells with endothelial cells and fibroblasts generated vascular networks during <i>in vitro</i> culture, which persisted through transplantation and enhanced <i>in vivo</i> vascularization. 7-days of <i>in vitro</i> culture supported enhanced survival of transplanted cells, though function in terms of insulin secretion and reduction of hyperglycemia was compromised. However, 3-days of preculture led to both improved survival and function of the stem cell-derived β cells, with transplant recipients demonstrating reduced fasting blood glucose levels. These studies demonstrate the potential and some constraints on the application of vascularization strategies to enhance function of stem cell-derived β cells with transplantation to extrahepatic sites.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"108-120"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574921","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":"Glutamate Drives Glioblastoma Invasion in Three-Dimensional Hyaluronic Acid Hydrogels.","authors":"Dana Wilkins, Sanjay Kumar","doi":"10.1177/19373341251410484","DOIUrl":"10.1177/19373341251410484","url":null,"abstract":"<p><p>Glioblastoma (GBM) tumors are characterized by an excess of extracellular glutamate, one important source of which is the tumor cells themselves. This abundance of glutamate promotes GBM proliferation, migration, and therapeutic resistance, and causes excitotoxicity in nearby neurons. However, despite glutamate's clear role in promoting GBM aggression, the exact mechanisms through which excess glutamate drives these phenotypes, particularly three-dimensional (3D) invasion, remain incompletely understood. To address this gap, we used a 3D brain-mimetic hyaluronic acid (HA) hydrogel to investigate the role of glutamate signaling in GBM 3D invasion. We demonstrate that inhibiting the glutamate <i>N</i>-methyl-d-aspartate receptor (NMDAR) reduces invasion from 3D tumorspheres, a result that is reproducible across multiple continuous culture models and a patient-derived xenograft cell line. We then conducted glutamate-driven invasion studies in 3D HA-based devices that can be microdissected to isolate and differentially analyze invasive and noninvasive cells. Transcriptomic analysis of invasive, noninvasive, and drug-treated populations of cells reveals that NMDAR inhibition suppresses several pathways associated with the mechanobiology of invasion, including matrix remodeling and collagen deposition. Correspondingly, supplementation with exogenous collagen VI partially rescued 3D invasion. Our work speaks to the potential value of biomaterial platforms for identifying the autocrine and paracrine mechanisms through which neurotransmitters fuel GBM invasion.Impact StatementGlutamate is an abundant signaling molecule in the glioblastoma (GBM) microenvironment and important driver of disease progression; however, the mechanisms through which glutamate promotes invasion in three-dimensional (3D) environments remain poorly understood. By combining engineered hyaluronic acid hydrogel platforms and transcriptomic analysis, we determine that blocking glutamate signaling through the <i>N</i>-methyl-d-aspartate receptor suppresses invasion in 3D by interfering with extracellular matrix remodeling processes. This work highlights the utility of biomaterial platforms in dissecting neurotransmitter signaling in GBM invasion.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"19373341251410484"},"PeriodicalIF":2.8,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13206641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147492273","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":"<i>In Vitro</i> Model Extracellular Matrix Maturation Under Variable Stress Conditions.","authors":"Christian A Boehm, Mahmoud Sesa, Vytautas Kucikas, Marc van Zandvoort, Kevin Linka, Stefanie Reese, Stefan Jockenhoevel","doi":"10.1177/19373341251359109","DOIUrl":"10.1177/19373341251359109","url":null,"abstract":"<p><p>The study aims to enhance the design process of tissue-engineered implants by evaluating the effects of scaffold reinforcement and cultivation conditions on extracellular matrix (ECM) development. The research investigates the hypothesis that mechanical stress drives ECM production and alignment. Furthermore, we have explored the potential of an <i>in silico</i> growth model to complement <i>in vitro</i> findings for accelerated development processes. The study employed fiber-reinforced and nonreinforced scaffolds fabricated using warp-knitted textiles and fibrin gel. Myofibroblasts embedded in the scaffolds were cultivated under static and dynamic conditions. ECM development was evaluated through mechanical testing, hydroxyproline assays, and microscopy, while an <i>in silico</i> growth model was used to predict ECM behavior. Static cultivation resulted in significant ECM development in both reinforced and nonreinforced samples, with nonreinforced scaffolds showing higher collagen content and alignment along the load direction. In contrast, dynamic cultivation inhibited ECM formation, potentially due to cross-contraction and washout effects. Fiber-reinforced scaffolds exhibited higher elasticity and sustained stress across cycles without structural damage. The <i>in silico</i> model provided valuable insights but overestimated mechanical properties due to limited validation data. Reinforced scaffolds maintained geometry and elasticity, suggesting suitability for load-bearing applications. Nonreinforced scaffolds facilitated higher ECM production but were prone to structural damage. Dynamic cultivation requires optimization, such as prestatic cultivation, to support ECM development. The combined <i>in vitro</i> and <i>in silico</i> approach offers a promising framework for scaffold design, reducing the reliance on iterative experimental processes.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"10-20"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610431","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":"The Impact of Vascular Supply on Endochondral Bone Regeneration in Centimeter-Sized Porous Chambers.","authors":"Leanne S de Silva, Casper J Kuijpers, Ellen M Van Cann, Antoine J W P Rosenberg, Robert J J van Es, Debby Gawlitta","doi":"10.1089/ten.tea.2025.0045","DOIUrl":"10.1089/ten.tea.2025.0045","url":null,"abstract":"<p><p>The current clinical treatment of large bone defects in humans primarily relies on autologous bone grafts. However, the use of autologous bone grafts can be limited by tissue availability, variable bone quality, and donor site morbidity. In response to these challenges, endochondral bone regeneration has emerged as a promising approach. This method mimics endochondral ossification by chondrogenically differentiating or stimulating cells of various cell sources into 'callus mimics' (CMs). We previously demonstrated the feasibility of endochondral bone regeneration in restoring bone defects using 'mesenchymal stromal cell' (MSC)-derived devitalized CMs in small and large animals. To scale up the size of treated defects using these CMs, we propose the introduction of a vascular supply. In this study, an arteriovenous (AV) loop was introduced as a vascular supply to devitalized 'MSCs'-derived CMs in a centimeter-scale porous chamber in rats. The extent of vascularization and remodeling was evaluated for chambers filled with CMs in the presence or absence of an AV loop at 4 and 8 weeks. While the AV loop's role in vascularization is established, our study uniquely shows that in a challenging <i>in vivo</i> setting with devitalized callus mimics, the AV loop was critical for initiating bone formation. Mineralization was observed in all groups <i>via</i> microCT, but bone tissue formed only in the AV loop group (50% of samples at 8 weeks), underscoring its influential role in supporting both vascular invasion and bone formation.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"21-30"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143149","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":"Disc-Derived Induced Pluripotent Stem Cells and Environmental Cues for Nucleus Pulposus Regeneration.","authors":"Lisanne T Laagland, Deepani W L Poramba Liyanage, Romain Desprat, Frank M Riemers, Corinde C Warmerdam, Mathis Soubeyrand, Paul Bensadoun, Keita Ito, Ollivier Milhavet, Anne Camus, Benjamin Gantenbein, Jean-Marc Lemaitre, Marianna A Tryfonidou","doi":"10.1177/19373341251359106","DOIUrl":"10.1177/19373341251359106","url":null,"abstract":"<p><p>Notochordal cells (NCs), abundantly found in the developing nucleus pulposus (NP), show potential for intervertebral disc regeneration because of their unique instructive and healthy matrix-producing capacity. However, NCs are lost early in life, and attempts at <i>in vitro</i> expansion have failed because they lose their specific phenotype. Therefore, much effort is focused on the generation of cells resembling the properties of healthy matrix-producing NP-like cells from human induced pluripotent stem cells (hiPSCs). They are considered a promising alternative for employing native NCs. Given the ongoing challenges in the field to fine-tune the differentiation protocol and obtain a high yield of mature matrix-producing cells, this study aims to build on the epigenetic memory and instructive capacity of healthy NP tissue. For this, we employed the epigenetic memory of tissue-specific hiPSCs derived from TIE2⁺ NP progenitor cells (NPPCs) and microenvironmental cues of decellularized porcine NC-derived matrix (dNCM), consisting of matrix components and bioactive factors to differentiate hiPSC into mature, healthy matrix-producing cells for NP repair. As a comparison, donor-matched minimally invasive peripheral blood mononuclear cell-derived hiPSCs were used. The results show that employing NPPC-derived hiPSCs instructed by natural cues provided by dNCM resulted in an increased expression of healthy phenotypic and matrisome-related NP markers. Furthermore, within this <i>in vitro</i> environment, differentiation of blood-derived hiPSC lines led to augmented differentiation into the hematopoietic and neural cell lineage. In conclusion, we demonstrate that hiPSCs derived from NPPCs achieve enhanced differentiation outcomes in the presence of dNCM, highlighting the potential impact of the epigenetic memory.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"54-67"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144612355","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":"Regenerative Potential of Human Umbilical Cord Vein for Urethral Reconstruction in Male Rabbit Model.","authors":"Clement Parat, Damien Carnicelli, Stephan Langonnet, Marc Sbizzera, Laurence Barnouin, Yao Chen, Laura Barrot, Paul Neuville, Nicolas Morel-Journel","doi":"10.1089/ten.tea.2025.0061","DOIUrl":"10.1089/ten.tea.2025.0061","url":null,"abstract":"<p><p>Tissue engineering offers an alternative for augmentation urethroplasty; however, no ideal material has yet been developed. Recently, materials derived from amniotic tissues appear to exhibit promising properties. Herein, the aim of this study was to provide a proof of concept for the integration of the human umbilical cord vein for urethral reconstructions in rabbits. Rabbits were included in two groups; the control group underwent urethral reconstruction using autograft urethral tissue, and the test group received xenograft tissue (umbilical cord vein) after creating a 1 × 1 cm defect in the proximal urethra. At 3 weeks, endoscopy and biopsy were performed. At 6 weeks, the animals were euthanized, and their urethra and corpus cavernosum were sent for histopathological analysis. The six rabbits exhibited favorable clinical and endoscopic progress with no fistula or stenosis. Biopsy analysis found no lesion of the urothelium and chorion. Final histological analysis found similar results in both groups: normal histology with moderate urothelium vacuolation and a weak inflammatory cellular infiltrate. The present study provides a proof of concept of human umbilical cord vein as a scaffold for urethral regeneration. This could be an alternative to existing urethral tissue grafting procedures that can have difficulties with integration or immunological tolerance; however, further research is required.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"1-9"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129644","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":"β3GALT2 Gene Promotes Osteogenic Differentiation of BMSCs on n-HA/PA66 Via Exosomes.","authors":"Lipeng Peng, Jian Yang, Linnan Wang, Qiujiang Li, Yueming Song","doi":"10.1089/ten.tea.2025.0013","DOIUrl":"10.1089/ten.tea.2025.0013","url":null,"abstract":"<p><p>While β3GalT2 has been implicated in osteogenic regulation, its synergistic application with bioactive scaffolds remains unexplored. This study pioneers a dual-functional bone regeneration strategy by integrating β3GalT2-engineered bone marrow mesenchymal stem cells (BMSCs-β3GalT2) with nano-hydroxyapatite/polyamide 66 (n-HA/PA66) composites. First, we studied the effect of β3GalT2 on rat BMSCs (rBMSCs) by overexpression the β3GalT2 gene. Following this, we extracted exosomes and verified that β3GalT2 influences osteogenesis of rBMSCs through exosomes. Subsequently, we inoculated these rBMSCs on n-HA/PA66 and demonstrated the effects of β3GalT2 and n-HA/PA66 on osteogenic differentiation of rBMSCs. On this basis, we also explored the molecular mechanism of β3GalT2 regulating M1 polarization through exosomes. Finally, we verified our study by using animal models of skull defect and femur defect. Our results suggest that β3GalT2 promotes osteogenic differentiation of rBMSCs through exosomes. At the same time, rBMSCs-β3GalT2 combined with n-HA/PA66 showed good osteogenic effect <i>in vivo</i> and <i>in vitro</i>. In addition, we also found that β3GalT2 can regulate M1 polarization through exosomes. Our findings establish β3GalT2 as a master regulator of osteogenesis through cellular-exosomal-circuitry mechanisms. The biohybrid system synergistically combines gene-enhanced stem cells with tunable biomaterials, representing a paradigm shift in bone tissue engineering.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"31-42"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144417","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":"Donor Variability and 3D Culture Models Influence Human Mesenchymal Stem Cell Differentiation.","authors":"Sarah Jones, Michelle Tai, Manish Ayushman, Abena Peasah, Julia Johannsen, Fan Yang","doi":"10.1089/ten.tea.2025.0028","DOIUrl":"10.1089/ten.tea.2025.0028","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) are widely used for tissue regeneration due to their multilineage differentiation potential and ability to secrete paracrine factors with immunomodulatory and angiogenic functions. Standard MSC differentiation protocols typically rely on two-dimensional (2D) or pellet culture models that are simple to use but not well-suited for translational or clinical applications. To promote better cell survival, tissue deposition, and differentiation of MSCs, a wide variety of three-dimensional (3D) biomaterial scaffolds and platforms have been developed that provide structural support and present a carefully defined set of biochemical and biophysical cues to cells. While biomaterials can guide cell behavior and promote desirable tissue regeneration outcomes, one remaining challenge in the field is inherent donor-to-donor variability in MSC behavior, phenotype, and differentiation capacity. Although MSCs are promising tools for regeneration, the influence of donor variability on MSC differentiation across culture models remains poorly understood. Previous studies typically use cells from a single donor or rely solely on standard culture models. To address these gaps, we compared MSCs from six human donors and assessed differentiation across chondrogenic, osteogenic, and adipogenic lineages using both standard (pellet or 2D) and 3D biomaterial-based culture models. Alginate hydrogels were used to assess chondrogenesis, while gelatin microribbon (µRB) hydrogels were used to evaluate osteogenesis and adipogenesis in 3D. Significant donor-to-donor variability was observed in differentiation outcomes across all three lineages and within both 2D and 3D culture models. By directly comparing donor variability in 2D and 3D, we provide evidence that standard 2D models cannot predict MSC differentiation capacity in 3D biomaterials. Therefore, to improve therapeutic efficacy and advance biomaterial-based strategies for tissue regeneration, it is critical to understand how donor variability affects MSC differentiation patterns across 3D biomaterial-based culture models.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"43-53"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13178311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129634","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":"Bioprinting the Osteochondral Interface: Advances, Challenges, and Future Directions.","authors":"Hang Truong, Murat Guvendiren","doi":"10.1177/19373341251410101","DOIUrl":"https://doi.org/10.1177/19373341251410101","url":null,"abstract":"<p><p>Osteochondral (OC) defects, involving simultaneous damage to articular cartilage and subchondral bone, remain clinically challenging due to the distinct biological, mechanical, and structural characteristics of each layer. Traditional repair techniques are limited by poor integration and inadequate tissue regeneration. 3D bioprinting has emerged as a promising strategy to fabricate biomimetic OC constructs with precise spatial control over scaffold architecture, cell distribution, and bioactive cues. This review summarizes recent advancements in additive manufacturing techniques and their applications in OC tissue engineering. Scaffold design strategies are discussed, along with the selection of biofunctional materials. Special focus is given to recent progress in bioink development, including the precise incorporation of growth factors, zonal patterning of stem cells to guide region-specific differentiation, and the integration of bioceramics to enhance osteogenic potential while supporting chondrogenic matrix formation.</p>","PeriodicalId":56375,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145866470","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}