Journal of Biomaterials Applications最新文献

{"title":"Potential of thermoresponsive hydrogel as an alternative therapy for rat knee osteoarthritis.","authors":"Yi Kung, Wei-Chun Chien, Hsin-Hsin Shen, Sen-Lu Chen, Wei-Lin Yu, Yu-Chi Wang, Wen-Shiang Chen, Chueh-Hung Wu","doi":"10.1177/08853282231208506","DOIUrl":"10.1177/08853282231208506","url":null,"abstract":"<p><p>Osteoarthritis is a degenerative condition that is highly prevalent and primarily affects the joints. The knee is the most commonly affected site, impacting the lives of over 300 million individuals worldwide. This study presents a potential solution to address the unmet need for a minimally invasive technique in the treatment of osteoarthritis: a biocompatible, injectable, and thermoresponsive hydrogel. In comparison to commercially available products such as lyophilized platelets, dextrose, and triamcinolone, the thermoresponsive hydrogel exhibits significantly superior performance in dynamic behaviors, including print area, stability, and step cycle, when tested on rats with knee osteoarthritis. However, it demonstrates similar treatment efficacy to these products in static behaviors, as observed through histopathological and immunohistochemical analysis. Therefore, the thermoresponsive hydrogel holds promise as an effective alternative therapy for osteoarthritis. Moreover, by blending the hydrogel with drugs, controlled and sustained release can be achieved, thereby facilitating the long-term management of osteoarthritis symptoms.</p>","PeriodicalId":15138,"journal":{"name":"Journal of Biomaterials Applications","volume":" ","pages":"707-718"},"PeriodicalIF":2.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49690642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nano-injectable pH/NIR-responsive hydrogel for chemo-photothermal synergistic drug delivery.","authors":"Qian Zhao, Xu Yue, Liu Miaomiao, Wang Yanming, Guolin Wu","doi":"10.1177/08853282231209653","DOIUrl":"10.1177/08853282231209653","url":null,"abstract":"<p><p>Conventional cancer treatments are highly toxic and ineffective; therefore, it is essential to develop less toxic and minimally invasive treatment methods. A pH/Near Infra-red (NIR) dual-responsive, nano-injectable smart hydrogel was fabricated by incorporating CuS nanoparticles into the hydrogel networks formed by a random copolymer of N-isopropylacrylamide (NIPAM) and double-bond functionalized uracil. Microstructural characterizations of synthesized polymer and hydrogels were carried out using transmission electron microscope (TEM), scanning electron microscope (SEM), nuclear magnetic resonance (NMR) and fourier transform infrared spectroscopy (FT-IR). Multiple hydrogen bonding interactions between uracils function as physical cross-linking points to construct the network structure of the polymeric nanogel without the addition of additional cross-linking agents, ensuring the material's safety. The amino group on the structure of uracil gives the uracil-modified polymeric hydrogel excellent pH responsiveness. Notably, as a temperature-responsive material, poly (N-isopropylacrylamide) (PNIPAM) nanogel solution can achieve in situ gel formation (within 100 s at 37°C) above its lower critical solution temperature (LCST), granting injectability to polymeric solutions. Moreover, using a hierarchical construction strategy, the variable loading of DOX and CuS was achieved. First, a heterogeneous system was created by encapsulating doxorubicin (DOX) inside the nanogel via hydrophobic and π-π stacking interactions, followed by the introduction of CuS nanoparticles as photosensitizers outside of the nanogels. Due to the presence of CuS nanoparticles, the gel is able to convert NIR light into local heat to enhance the destruction of tumor cells while simultaneously achieving rapid in situ gel formation. The in situ-forming hydrogel showed promising tissue biocompatibility. The in vitro antitumor test demonstrated the capacity of the nanocomposite hydrogel for chemo-photothermal synergistic therapy. Therefore, this prepared platform has the potential to become a safe and effective, smart-responsive drug carrier for chemotherapy and PTT synergy, a minimally invasive material for tumor treatment.</p>","PeriodicalId":15138,"journal":{"name":"Journal of Biomaterials Applications","volume":" ","pages":"614-628"},"PeriodicalIF":2.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71423867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A preliminary <i>In Vitro</i> viability study of an electrically active hernia mesh on mouse fibroblasts.","authors":"Victoria Drapal, Savannah Mosier, Anna Norman, German Berbel, Jennifer L Robinson, Elizabeth A Friis","doi":"10.1177/08853282231209312","DOIUrl":"10.1177/08853282231209312","url":null,"abstract":"<p><p>Hernias occur when part of an organ, typically the intestines, protrudes through a disruption of the fascia in the abdominal wall, leading to patient pain, discomfort, and surgical intervention. Over one million hernia repair surgeries occur annually in the USA, but globally, hernia surgeries can exceed 20 million. Standard practice includes hernia repair mesh to help hold the compromised tissue together, depending on where the fascial disruption is located and the patient's condition. However, the recurrence rate for hernias after using the most common type of hernia mesh, synthetic, is currently high. Physiological-level electrical stimulation (ES) has shown beneficial effects in improving healing in soft tissue regeneration. Piezoelectric materials can produce low-level electrical signals from mechanical loading to help speed healing. Combining the novelty of piezo elements to create an electrically active hernia repair mesh for faster healing prospects is explored in this study through simulated transcutaneous mechanical loading of the piezo element with therapeutic ultrasound. A tissue phantom was developed using Gelatin #0 and Metamucil® to better simulate a clinical application of the therapeutic ultrasound loading modality. The cellular viability of varying ultrasound intensities and temporal effects was analyzed. Overall, minimal cytotoxicity was observed across all experimental groups during the ultrasound intensity and temporal viability studies.</p>","PeriodicalId":15138,"journal":{"name":"Journal of Biomaterials Applications","volume":" ","pages":"662-669"},"PeriodicalIF":2.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11181991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49677755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrospun poly (ε-caprolactone)/beeswax based super-hydrophobic anti-adhesive nanofibers as physical barriers for impeding fibroblasts invasion.","authors":"B Sowmya, Prasanta Kumar Panda","doi":"10.1177/08853282231212604","DOIUrl":"10.1177/08853282231212604","url":null,"abstract":"<p><p>Super-hydrophobic electrospun membranes are very essential barrier materials to physically isolate the wound site in order to prevent adhesions and for restoring the normal functioning of the surrounding tissues and organs. In the present study, poly (ε-caprolactone) (PCL)/beeswax (BW) based nanofibrous anti-adhesion membranes were fabricated by electrospinning technique. The BW concentration was varied from 10 to 30 wt.%. The nanofibers were evaluated for their morphological and physio-chemical properties. The electrospun mats demonstrate random distribution of nanofibers. Surface wettability was evaluated using static water contact angle method. PCL/BW (70/30) membrane had shown super-hydrophobicity (contact angle = 150°). From the cell culture studies, it was evident that cell viability, adhesion and proliferation of L929 cells on PCL/BW (70/30) membrane were comparatively lower than those on pure PCL membrane due to its super-hydrophobic nature. Consequently, PCL/BW (70/30) membrane was found as a potential candidate for fibroblast (L929) cell anti-adhesion applications.</p>","PeriodicalId":15138,"journal":{"name":"Journal of Biomaterials Applications","volume":" ","pages":"681-691"},"PeriodicalIF":2.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71481839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Ag NPs/allantoin loaded PCL/GEL electrospun nanofibers for topical wound treatment.","authors":"Mohsen Doostmohammadi, Seyyed Vahid Niknezhad, Hamid Forootanfar, Younes Ghasemi, Elham Jafari, Mahboubeh Adeli-Sardou, Armin Amirsadeghi, Alieh Ameri","doi":"10.1177/08853282231212605","DOIUrl":"10.1177/08853282231212605","url":null,"abstract":"<p><p>In the present study, the allantoin and silver nanoparticle (Ag NPs) loaded poly caprolactone/gelatin (PCL/GEL) nanofibers produced using electrospinning technique and their cyto-compatibility and wound healing activity were evaluated in vitro and in vivo. The SEM imaging revealed diameters of 278.8 ± 10 and 240.6 ± 12 nm for PCL/GEL/Ag NPs and PCL/GEL/Ag NPs/allantoin scaffolds. The Ag NPs entrapment into scaffolds was evaluated by FTIR analysis and EDX mapping. Both scaffolds containing Ag NPs and Ag NPs/allantoin exhibited valuable wound healing activity in Wistar rat animal model. The profound granulation tissue formation, high collagen deposition in coordination with low level of edema and inflammatory cells in Ag NPs/allantoin loaded scaffolds resulted in complete and mature re-epithelialization in giving the healing score (12 out of 12) equal to positive control group to the wounds treated with these scaffolds. It was concluded that the Ag NPs/allantoin loaded scaffolds regarding to their good antibacterial activity and excellent wound healing activity could be introduced as new effective wound dressing materials.</p>","PeriodicalId":15138,"journal":{"name":"Journal of Biomaterials Applications","volume":" ","pages":"692-706"},"PeriodicalIF":2.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71412368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proliferation and differentiation of MC3T3-E1 cells on polymethyl methacrylate cements containing Fe₃O₄ and TiO₂ for hyperthermic treatment of metastatic bone tumors.","authors":"Moe Kubota, Maiko Furuya, Kotone Yokota, Hiroyasu Kanetaka, Tomoyuki Ogawa, Shin Saito, Balachandran Jeyadevan, Masaya Shimabukuro, Taishi Yokoi, Masakazu Kawashita","doi":"10.1177/08853282231205681","DOIUrl":"10.1177/08853282231205681","url":null,"abstract":"<p><p>Polymethyl methacrylate (PMMA) bone cement is widely used to relieve pain caused by metastatic bone tumors. We previously found that PMMA bone cement containing 15 mass% or more of TiO₂ showed good apatite-forming ability, and 25 mass% or more of Fe₃O₄ generated sufficient heat for hyperthermia under an alternating current (AC) magnetic field. In this study, the cytocompatibility of PMMA bone cement with Fe₃O₄:TiO₂ weight ratios of 25:15 (F25T15-3/2-42) and 30:15 (F30T15-3/2-42) was evaluated using osteoblastic cells (MC3T3-E1). The proliferation and differentiation of MC3T3-E1 cells were suppressed for F25T15-3/2-42 and F30T15-3/2-42 compared to PMMA bone cement without Fe₃O₄ and TiO₂ (F0T0-3/2-42). The release of methyl methacrylate (MMA) monomers from F25T15-3/2-42 and F30T15-3/2-42 at 7 days was about 33 and 50 times higher than that from F0T0-3/2-42, respectively. The remarkable release of MMA monomers from F25T15-3/2-42 and F30T15-3/2-42 may be responsible for the suppressed proliferation and differentiation of MC3T3-E1 cells. The release of MMA monomers was not reduced when the MMA/PMMA weight ratio was decreased from 3/2 to 1/1, however, it was significantly reduced by increasing the content of benzoyl peroxide (BPO) and <i>N</i>, <i>N</i>-dimethyl-<i>p</i>-toluidine (DMPT) to 8 and 4 mass% against MMA, respectively. Proliferation and differentiation of MC3T3-E1 cells on PMMA-type cements containing Fe₃O₄ and TiO₂ with increased BPO and DMPT contents need to be investigated in the future; however, our findings will be useful for designing PMMA cements for the hyperthermic treatment of metastatic bone tumors.</p>","PeriodicalId":15138,"journal":{"name":"Journal of Biomaterials Applications","volume":" ","pages":"605-613"},"PeriodicalIF":2.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41140311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silk fibroin nanoparticles and β-tricalcium phosphate loaded tissue engineered gelatin bone scaffolds: A Nature-based, low-cost solution.","authors":"Ayşegül Yıldız, Mehmet Birer, Yağmur Turgut Birer, Recep Uyar, Begüm Yurdakök-Dikmen, Füsun Acartürk","doi":"10.1177/08853282231207578","DOIUrl":"10.1177/08853282231207578","url":null,"abstract":"<p><p>Tissue engineering has recently attracted attention as an alternative to traditional treatment methods for tissue and organ damage. Since bone is one of the most important vital parts of the body, the treatment of bone damage is important. Silk fibroin is a natural polymer with properties such as biocompatibility and biodegradability, which attracts attention with its controlled release, especially in drug delivery systems. In this study, gelatin-based scaffolds loaded with silk fibroin nanoparticles and β -tricalcium phosphate (β -TCP) were developed to be used as a potential drug delivery system in bone tissue engineering. The chosen nanoparticle formulation has a 294 nm average diameter with a 0.380 polidispersity index (PDI). In vitro characterization of scaffolds was performed by mechanical, morphological characterization, swelling capacity, Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FT-IR) measurements, and biocompatibility was evaluated by cell culture studies. Swelling index, tensile strength, elongation at break, and Young modulus of the β -TCP and silk nanoparticles loaded scaffold were found as 456%, 1.476 MPa, 6.75%, and 24 MPa, respectively. In vitro cell culture studies have shown that scaffolds prepared in the present study can accelerate osteoblast differentiation and increase the healing rate of bone tissues. In addition, they have the potential to be used as a drug delivery system in bone tissue engineering that needs to be evaluated with further studies.</p>","PeriodicalId":15138,"journal":{"name":"Journal of Biomaterials Applications","volume":" ","pages":"646-661"},"PeriodicalIF":2.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54229207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imperfect cross-linking of xanthan for pH-responsive bio-based composite moist wound dressings by stencil printing.","authors":"Florian Wurm, Margit Lenninger, Astrid Mayr, Cornelia Lass-Floerl, Tung Pham, Thomas Bechtold","doi":"10.1177/08853282231210712","DOIUrl":"10.1177/08853282231210712","url":null,"abstract":"<p><p>The work addresses the use of bio-based and -degradable materials for the production of a moist, adaptive and anti-microbial wound dressing. The dressing is targeted to exhibit a pH-dependent active agent release. Xanthan hydrogel structures are coated on cellulose fabrics via stencil printing and subsequently cross-linked using glyoxal. By alteration of the cross-linker content from 1 to 6% by mass, the hydrogel elasticity can be tuned within a range of 2-16 kPa storage modulus. Increasing initial glyoxal concentrations also result in higher amounts of glyoxal release. Glyoxal, an anti-microbial agent with approval in veterinary medicine, is mostly released upon wound application supporting infection management. As wound simulation, normal saline, as pH 5 and pH 8 buffer solutions, were used. The release profile and magnitude of approx. 65%-90% glyoxal is pH-dependent. Increased release rates of glyoxal are present in pH 8 fluids, which mostly base on faster hydrogel swelling. Higher total glyoxal release is present in pH 5 fluid and normal saline after 3 days. Accordingly, a pH-dependent release profile was encountered. As glyoxal attacks any cell unselectively, it is expected to be effective against antibiotic resistant bacteria. By stencil printing the dressing size can be adjusted to minimize healthy glyoxal tissue exposure.</p>","PeriodicalId":15138,"journal":{"name":"Journal of Biomaterials Applications","volume":" ","pages":"670-680"},"PeriodicalIF":2.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71481840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The efficiency of fabricated Ag/ZnO nanocomposite using <i>Ruta chalepensis</i> L. leaf extract as a potent protoscolicidal and anti-hydatid cysts agent.","authors":"Parwin J Jalil, Bushra H Shnawa, Samir M Hamad, Bnar Shahab Hamad, Mukhtar H Ahmed","doi":"10.1177/08853282231207236","DOIUrl":"10.1177/08853282231207236","url":null,"abstract":"<p><strong>Background: </strong>As a consequence of their eco-friendliness, simplicity and non-toxicity, the fabrication of metal and metal oxide nanoparticles using greener chemistry has been a highly attractive research area over the last decade.</p><p><strong>Aim: </strong>In this study focused on the fabrication of silver-Zinc oxide nanocomposite (Ag-ZnO NCs) using <i>Ruta chalepensis</i> leaf extract and evaluating its potential biological activities, against <i>Echinococcus granulosus</i> in an in vitro and in vivo model using BALB/c mice.</p><p><strong>Methods: </strong>In this study, the synthesis of Ag-ZnO NCs was accomplished using local <i>R. chalepensis</i> leaf extracts. The synthesized nanocomposites were identified using UV-Vis, SEM-EDX, XRD, and FTIR. For a short-term assessment of acute toxicity, BALB/c mice were given the prepared NCs orally. Dual sets of mice were also intraperitoneally injected with protoscoleces for secondary echinococcosis infection. Furthermore, a blood compatibility test was carried out on the nanocomposites.</p><p><strong>Results: </strong>The synthesized Ag-ZnO NCs presented a surface plasmon peak at 329 and 422 nm. The XRD, SEM, and EDX confirmed the purity of the Ag-ZnO NCs. The FTIR spectra indicated the formation of Ag-ZnO NCs. Compared to the untreated infected mice, the treated-infected animals displayed an alteration in the appearance of the hepatic hydatid cysts from hyaline to whitish cloudy with a rough surface appearance. Lysis of RBCs at various doses of Ag-ZnONCs was significantly less than the positive contro,.</p><p><strong>Conclusion: </strong>These findings revealed that the Ag-ZnO NCs didn't cause any adverse symptoms and no mortality was observed in all administered groups of mice. The obtained outcomes confirmed that concentrations of up to 40 μg/mL of the bio-fabricated Ag-ZnONCs induced no notable harm to the red blood cells.</p>","PeriodicalId":15138,"journal":{"name":"Journal of Biomaterials Applications","volume":" ","pages":"629-645"},"PeriodicalIF":2.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41235584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in soluble decellularized extracellular matrix for heart tissue engineering and organ modeling.","authors":"Golara Kafili, Hannaneh Kabir, Amirhossein Jalali Kandeloos, Elham Golafshan, Sara Ghasemi, Shohreh Mashayekhan, Nayere Taebnia","doi":"10.1177/08853282231207216","DOIUrl":"10.1177/08853282231207216","url":null,"abstract":"<p><p>Despite the advent of tissue engineering (TE) for the remodeling, restoring, and replacing damaged cardiovascular tissues, the progress is hindered by the optimal mechanical and chemical properties required to induce cardiac tissue-specific cellular behaviors including migration, adhesion, proliferation, and differentiation. Cardiac extracellular matrix (ECM) consists of numerous structural and functional molecules and tissue-specific cells, therefore it plays an important role in stimulating cell proliferation and differentiation, guiding cell migration, and activating regulatory signaling pathways. With the improvement and modification of cell removal methods, decellularized ECM (dECM) preserves biochemical complexity, and bio-inductive properties of the native matrix and improves the process of generating functional tissue. In this review, we first provide an overview of the latest advancements in the utilization of dECM in <i>in vitro</i> model systems for disease and tissue modeling, as well as drug screening. Then, we explore the role of dECM-based biomaterials in cardiovascular regenerative medicine (RM), including both invasive and non-invasive methods. In the next step, we elucidate the engineering and material considerations in the preparation of dECM-based biomaterials, namely various decellularization techniques, dECM sources, modulation, characterizations, and fabrication approaches. Finally, we discuss the limitations and future directions in fabrication of dECM-based biomaterials for cardiovascular modeling, RM, and clinical translation.</p>","PeriodicalId":15138,"journal":{"name":"Journal of Biomaterials Applications","volume":"38 5","pages":"577-604"},"PeriodicalIF":2.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138433979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}