Journal of Functional Biomaterials最新文献

{"title":"Electrospun Silk-ICG Composite Fibers and the Application toward Hemorrhage Control.","authors":"Ayesha Siddiqua, Elwin Clutter, Olga Garklavs, Hemalatha Kanniyappan, Rong R Wang","doi":"10.3390/jfb15090272","DOIUrl":"https://doi.org/10.3390/jfb15090272","url":null,"abstract":"<p><p>In trauma and surgery, efficient hemorrhage control is crucial to avert fatal blood loss and increase the likelihood of survival. There is a significant demand for novel biomaterials capable of promptly and effectively managing bleeding. This study aimed to develop flexible biocomposite fibrous scaffolds with an electrospinning technique using silk fibroin (SF) and indocyanine green (ICG). The FDA-approved ICG dye has unique photothermal properties. The water permeability, degradability, and biocompatibility of Bombyx mori cocoon-derived SF make it promising for biomedical applications. While as-spun SF-ICG fibers were dissolvable in water, ethanol vapor treatment (EVT) effectively induced secondary structural changes to promote β-sheet formation. This resulted in significantly improved aqueous stability and mechanical strength of the fibers, thereby increasing their fluid uptake capability. The enhanced SF-ICG interaction effectively prevented ICG leaching from the composite fibers, enabling them to generate heat under NIR irradiation due to ICG's photothermal properties. Our results showed that an SF-ICG 0.4% fibrous matrix can uptake 473% water. When water was replaced by bovine blood, a 25 s NIR irradiation induced complete blood coagulation. However, pure silk did not have the same effect. Additionally, NIR irradiation of the SF-ICG fibers successfully stopped the flow of blood in an in vitro model that mimicked a damaged blood vessel. This novel breakthrough offers a biotextile platform poised to enhance patient outcomes across various medical scenarios, representing a significant milestone in functional biomaterials.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"15 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11433354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347877","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":"Application of the Self-Assembling Peptide Hydrogel RADA16 for Hemostasis during Tonsillectomy: A Feasibility Study.","authors":"Joshua Michaels, Anna I Kaleva, Laura Bateman, Oliver Wakelam, Joanna Stephens","doi":"10.3390/jfb15090271","DOIUrl":"https://doi.org/10.3390/jfb15090271","url":null,"abstract":"<p><p>Tonsillectomy is a common surgical procedure but carries a high risk of readmission for secondary bleeding and pain. This study evaluated the feasibility and effectiveness of using the hemostatic self-assembling peptide hydrogel RADA16 (PuraBond, 3-D Matrix SAS; Caluire et Cuire, France) to control bleeding from the tonsillectomy wound bed. Readmission/re-operation rates were compared between a prospective case series of 21 primarily adult tonsillectomy patients treated with topical RADA16 and an untreated historical Control group of 164 patients who underwent tonsillectomy by 10 surgeons at a single tertiary hospital in the UK between March 2019 and June 2022. Cumulative readmission rates for any reason were 2-fold elevated in Control subjects (18.9%; <i>n</i> = 31/164 subjects) compared to patients treated intra-operatively with RADA16 hemostatic hydrogel (9.5%; <i>n</i> = 2/21) (<i>p</i> = 0.378). Readmission rates for postoperative bleeding were 3-fold higher in Controls (14.6%; <i>n</i> = 24/164 subjects) than in the RADA16-treated group (4.8%; <i>n</i> = 1/21) (<i>p</i> = 0.317). A similar rate of retreatment for pain was recorded in the Control (4.3%; <i>n</i> = 7/164) and RADA16 (4.8%; <i>n</i> = 1/21) groups (<i>p</i> = 0.999). Two Control subjects (1.2%) required re-operation for recalcitrant bleeding; no RADA16 subject (0.0%) required re-operation for any reason. No device-related adverse events occurred in the RADA16 group. Surgeons were pleased with the easy learning curve and technical feasibility associated with intra-operatively administering RADA16 hemostatic hydrogel. Intra-operative hemostasis using RADA16 peptide hydrogel was straightforward and was associated with a trend of 3-fold lower rates of readmission for postoperative bleeding events than untreated Control subjects.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"15 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11432850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142336441","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":"Regeneration of Critical Calvarial Bone Defects Using Bovine Xenograft, Magnesium-Enriched Bovine Xenograft and Autologous Dentin in Rats: Micro-CT, Gene Expression and Immunohistochemical Analysis.","authors":"Marija Čandrlić, Ana Terezija Jerbić Radetić, Hrvoje Omrčen, Barbara Franović, Lara Batičić, Tamara Gulić, Tea Čaljkušić-Mance, Sanja Zoričić Cvek, Lucija Malešić, Željka Perić Kačarević, Olga Cvijanović Peloza","doi":"10.3390/jfb15090270","DOIUrl":"https://doi.org/10.3390/jfb15090270","url":null,"abstract":"<p><p>The aim of this study was to evaluate the efficacy of autologous dentin (AD), bovine xenograft (BX) and magnesium-enriched bovine xenograft (BX + Mg) in the healing of critical cranial bone defects (CCBDs) in rats. Eighty male Wistar rats were divided into four groups: BX, BX + Mg, AD and the control group (no intervention). Eight mm CCBDs were created and treated with the respective biomaterials. Healing was assessed 7, 15, 21 and 30 days after surgery by micro-computed tomography (micro-CT), real-time polymerase chain reaction (RT-PCR) and immunohistochemical analysis. Micro-CT analysis showed that AD had the highest bone volume and the least amount of residual biomaterial at day 30, indicating robust bone formation and efficient resorption. BX + Mg showed significant bone volume but had more residual biomaterial compared to AD. RT-PCR showed that the expression of osteocalcin (OC), the receptor activator of nuclear factor κB (RANK) and sclerostin (SOST), was highest in the AD group at day 21 and vascular endothelial growth factor (VEGF) at day 15, indicating increased osteogenesis and angiogenesis in the AD group. Immunohistochemical staining confirmed intense BMP-2/4 and SMAD-1/5/8 expression in the AD group, indicating osteoinductive properties. The favorable gene expression profile and biocompatibility of AD and BX + Mg make them promising candidates for clinical applications in bone tissue engineering. Further research is required to fully exploit their potential in regenerative surgery.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"15 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11433293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347983","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":"Impact of Calcium Lactate Pretreatment on Enamel Fluoride Uptake: A Comparative In Vitro Study of Different Fluoride Types and Concentrations.","authors":"Fjolla Kullashi Spahija, Ivana Sutej, Kresimir Basic, Kreshnik Spahija, Kristina Peros","doi":"10.3390/jfb15090269","DOIUrl":"https://doi.org/10.3390/jfb15090269","url":null,"abstract":"<p><p>(1) Background: This study aimed to establish the effect of calcium lactate enamel pretreatment related to different fluoride types and concentrations on the enamel uptake of alkali-soluble fluorides. (2) Materials: In a blind and randomized in vitro study, a total of 60 teeth are used. The first 30 teeth were cut and randomly allocated into one of the following treatments: (A) calcium lactate pretreatment followed by three different fluoride solutions; (B) the \"Fluoride only\" group, with slabs treated with three different fluoride solutions; (C) the \"Calcium only\" group, with slabs treated with calcium lactate solution; (D) slabs treated with deionized water (negative control group). The next 30 teeth underwent all the above described group procedures but were treated with lower fluoride concentrations. Fluoride was extracted from enamel using 1 M KOH solution and analyzed using a fluoride ion-specific electrode. (3) Results: The findings revealed that slabs treated with NaF following calcium lactate pretreatment exhibited significantly greater enamel uptake of alkali-soluble fluoride compared to other substrates. This significant effect was not observed at lower fluoride concentrations. (4) Conclusion: The study demonstrates that pretreatment with calcium lactate followed by treatment with NaF at 226 ppm F significantly enhances the uptake of alkali-soluble fluoride in enamel compared to other fluoride types.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"15 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11433163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347973","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":"Functional Biomaterials and Biomaterial Composites with Antimicrobial Properties.","authors":"John H T Luong","doi":"10.3390/jfb15090267","DOIUrl":"https://doi.org/10.3390/jfb15090267","url":null,"abstract":"<p><p>AMR occurs when bacteria, viruses, fungi, and parasites no longer respond to antimicrobial medicines, including antibiotics, antivirals, antifungals, and antiparasitics [...].</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"15 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11433040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347879","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":"Stress Distribution of Pediatric Zirconia and Stainless Steel Crowns after Pulpotomy Procedure under Vertical Loading: A Patient-Specific Finite Element Analysis.","authors":"Özgür Doğan","doi":"10.3390/jfb15090268","DOIUrl":"https://doi.org/10.3390/jfb15090268","url":null,"abstract":"<p><p><b>Aim:</b> With modern dentistry advancements, children and parents have significantly raised aesthetic expectations in pediatric dentistry. Pediatric zirconia crowns (PZCs) provide a superior aesthetic appearance compared with stainless steel crowns (SSCs), making them a popular treatment option. However, a comparison of the compressive stresses caused by these crowns on the roots of primary teeth and alveolar bones has not been conducted. <b>Materials and Methods:</b> Cone beam computed tomography (CBCT) images of an eight-year-old female patient who experienced premature loss of a primary mandibular left second molar were obtained from a dental hospital database. Rhinoceros 4.0 software was used to process and simulate images. Under simulated chewing forces, stress on the PZC, SSC, and intact primary first molars as control groups, as well as their roots and alveolar bone structures, was assessed with finite element analysis. <b>Statistical Analyses:</b> Depending on whether the descriptive data were normally distributed, the Student t-test and Mann-Whitney U test were used. Quantitative variables differ between the two categories of qualitative variables. One-way ANOVA and Kruskal-Wallis H tests were used depending on standard distribution assumptions. <i>p</i> < 0.05 indicates statistical significance differences. <b>Results:</b> PZCs, SSCs, and cement layers were stressed according to von Mises values, while roots and alveolar bones were stressed according to maximum and minimum stress values. When assessing crowns, SSCs exhibited the highest von Mises stress values, followed by PZCs and control groups (<i>p</i> < 0.001). In the cement layer, SSCs obtained significantly higher values (<i>p</i> = 0.003). In the root area, minimum principal stress values are more critical. The highest values were obtained from the intact tooth, PZC, and SSC, respectively (<i>p</i> < 0.001). Alveolar bones did not differ significantly in minimum principal stress (<i>p</i> = 0.950). <b>Conclusions:</b> Restorative full-coverage crowns exhibited higher von Mises values than intact teeth, as per current research findings. The von Mises values were highest in SSC, while lowest in PZC. As a result of this condition, the cement layer and root areas had higher von Mises stress and compressive stress. Alveolar bones were not affected regardless of restoration type. PZC transmits higher stress due to its properties.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"15 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11432998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347986","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":"In Vitro Wound-Healing Potential of Phenolic and Polysaccharide Extracts of <i>Aloe vera</i> Gel.","authors":"Andreea Iosageanu, Elena Mihai, Ana-Maria Seciu-Grama, Elena Utoiu, Alexandra Gaspar-Pintiliescu, Florentina Gatea, Anisoara Cimpean, Oana Craciunescu","doi":"10.3390/jfb15090266","DOIUrl":"https://doi.org/10.3390/jfb15090266","url":null,"abstract":"<p><p>The present study aimed to conduct a comparative investigation of the biological properties of phenolic and polysaccharide extracts obtained using an ultrasound-assisted technique from <i>Aloe vera</i> gel and their effects on each stage of the wound healing process in in vitro experimental models. HPLC analysis showed that the phenolic extract contained aloin, ferulic, and caffeic acid, as well as quercetin dihydrate, as major compounds. Capillary zone electrophoresis indicated the prevalence of mannose and glucose in the polysaccharide extract. Cell culture testing revealed the anti-inflammatory properties of the phenolic extract at a concentration of 0.25 mg/mL through significant inhibition of pro-inflammatory cytokines-up to 28% TNF-α and 11% IL-8 secretion-in inflamed THP-1-derived macrophages, while a pro-inflammatory effect was observed at 0.5 mg/mL. The phenolic extract induced 18% stimulation of L929 fibroblast proliferation at a concentration of 0.5 mg/mL, enhanced the cell migration rate by 20%, and increased collagen type I synthesis by 18%. Moreover, the phenolic extract exhibited superior antioxidant properties by scavenging free DPPH (IC₅₀ of 2.50 mg/mL) and ABTS (16.47 mM TE/g) radicals, and 46% inhibition of intracellular reactive oxygen species (ROS) production was achieved. The polysaccharide extract demonstrated a greater increase in collagen synthesis up to 25%, as well as antibacterial activity against <i>Staphylococcus aureus</i> with a bacteriostatic effect at 25 mg/mL and a bactericidal one at 50 mg/mL. All these findings indicate that the phenolic extract might be more beneficial in formulations intended for the initial phases of wound healing, such as inflammation and proliferation, while the polysaccharide extract could be more suitable for use during the remodeling stage. Moreover, they might be combined with other biomaterials, acting as efficient dressings with anti-inflammatory, antioxidant, and antibacterial properties for rapid recovery of chronic wounds.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"15 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11433545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347974","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":"Exploring the Role of Fibrin Gels in Enhancing Cell Migration for Vasculature Formation.","authors":"Joana A Moura, Hugh J Barlow, Shareen H Doak, Karl Hawkins, Iris Muller, Martin J D Clift","doi":"10.3390/jfb15090265","DOIUrl":"https://doi.org/10.3390/jfb15090265","url":null,"abstract":"<p><p>A hallmark of angiogenesis is the sprouting of endothelial cells. To replicate this event in vitro, biomaterial approaches can play an essential role in promoting cell migration. To study the capacity of a scaffold of fibrin (fibrinogen:thrombin mix) to support the movement of the endothelial cells, the migration area of spheroids formed with the HULEC cell line was measured. The cells were first allowed to form a spheroid using the hanging drop technique before being encapsulated in the fibrin gel. The cells' migration area was then measured after two days of embedding in the fibrin gel. Various conditions affecting fibrin gel polymerization, such as different concentrations of fibrinogen and thrombin, were evaluated alongside rheology, porosity, and fiber thickness analysis to understand how these factors influenced cell behavior within the composite biomaterial. Data point toward thrombin's role in governing fibrin gel polymerization; higher concentrations result in less rigid gels (loss tangent between 0.07 and 0.034) and increased cell migration (maximum concentration tested: 5 U/mL). The herein presented method allows for a more precise determination of the crosslinking conditions of fibrin gel that can be used to stimulate angiogenic sprouting.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"15 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11432887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347878","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":"Comparison of Key Properties of Ag-TiO₂ and Hydroxyapatite-Ag-TiO₂ Coatings on NiTi SMA.","authors":"Karolina Dudek, Aleksandra Strach, Daniel Wasilkowski, Bożena Łosiewicz, Julian Kubisztal, Anna Mrozek-Wilczkiewicz, Patryk Zioła, Adrian Barylski","doi":"10.3390/jfb15090264","DOIUrl":"https://doi.org/10.3390/jfb15090264","url":null,"abstract":"<p><p>To functionalize the NiTi alloy, multifunctional innovative nanocoatings of Ag-TiO₂ and Ag-TiO₂ doped with hydroxyapatite were engineered on its surface. The coatings were thoroughly characterized, focusing on surface topography and key functional properties, including adhesion, surface wettability, biocompatibility, antibacterial activity, and corrosion resistance. The electrochemical corrosion kinetics in a simulated body fluid and the mechanisms were analyzed. The coatings exhibited hydrophilic properties and were biocompatible with fibroblast and osteoblast cells while also demonstrating antibacterial activity against <i>E. coli</i> and <i>S. epidermidis</i>. The coatings adhered strongly to the NiTi substrate, with superior adhesion observed in the hydroxyapatite-doped layers. Conversely, the Ag-TiO₂ layers showed enhanced corrosion resistance.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"15 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11433350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347970","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":"Effects of Confined Microenvironments with Protein Coating, Nanotopography, and TGF-β Inhibitor on Nasopharyngeal Carcinoma Cell Migration through Channels.","authors":"Xiao Hong, Yuanhao Xu, Stella W Pang","doi":"10.3390/jfb15090263","DOIUrl":"https://doi.org/10.3390/jfb15090263","url":null,"abstract":"<p><p>Distant metastasis is the primary cause of unsuccessful treatment in nasopharyngeal carcinoma (NPC), suggesting the crucial need to comprehend this process. A tumor related to NPC does not have flat surfaces, but consists of confined microenvironments, proteins, and surface topography. To mimic the complex microenvironment, three-dimensional platforms with microwells and connecting channels were designed and developed with a fibronectin (FN) coating or nanohole topography. The potential of the transforming growth factor-β (TGF-β) inhibitor (galunisertib) for treating NPC was also investigated using the proposed platform. Our results demonstrated an increased traversing probability of NPC43 cells through channels with an FN coating, which correlated with enhanced cell motility and dispersion. Conversely, the presence of nanohole topography patterned on the platform bottom and the TGF-β inhibitor led to a reduced cell traversing probability and decreased cell motility, likely due to the decrease in the F-actin concentration in NPC43 cells. This study highlights the significant impact of confinement levels, surface proteins, nanotopography, and the TGF-β inhibitor on the metastatic probability of cancer cells, providing valuable insights for the development of novel treatment therapies for NPC. The developed platforms proved to be useful tools for evaluating the metastatic potential of cells and are applicable for drug screening.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"15 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11433299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347875","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}