Biomedical materials最新文献

{"title":"Optimization of polycaprolactone fibrous scaffold for heart valve tissue engineering","authors":"S. Jana, Amrita Bhagia, A. Lerman","doi":"10.1088/1748-605X/ab3d24","DOIUrl":"https://doi.org/10.1088/1748-605X/ab3d24","url":null,"abstract":"Pore size is generally small in nanofibrous scaffolds prepared by electrospinning polymeric solutions. Increase of scaffold thickness leads to decrease in pore size, causing impediment to cell infiltration into the scaffolds during tissue engineering. In contrast, comparatively larger pore size can be realized in microfibrous scaffolds prepared from polymeric solutions at higher concentrations. Further, microfibrous scaffolds are conducive to infiltration of reparative M2 phenotype macrophages during in vivo/in situ tissue engineering. However, rise of mechanical properties of a fibrous scaffold with the increase of polymer concentration may limit the functionality of a scaffold-based, tissue-engineered heart valve. In this study, we developed microfibrous scaffolds from 14%, 16% and 18% (wt/v) polycaprolactone (PCL) polymer solutions prepared with chloroform solvent. Porcine valvular interstitial cells were cultured in the scaffolds for 14 d to investigate the effect of microfibers prepared with different PCL concentrations on the seeded cells. Further, fresh microfibrous scaffolds were implanted subcutaneously in a rat model for two months to investigate the effect of microfibers on infiltrated cells. Cell proliferation, and its morphologies, gene expression and deposition of different extracellular matrix proteins in the in vitro study were characterized. During the in vivo study, we characterized cell infiltration, and myofibroblast and M1/M2 phenotypes expression of the infiltrated cells. Among different PCL concentrations, microfibrous scaffolds from 14% solution were suitable for heart valve tissue engineering for their sufficient pore size and low but adequate tensile properties, which promoted cell adhesion to and proliferation in the scaffolds, and effective gene expression and extracellular matrix deposition by the cells in vitro. They also encouraged the cells in vivo for their infiltration and effective gene expression, including M2 phenotype expression.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2019-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab3d24","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44268909","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 vivo therapeutic effect of wollastonite and hydroxyapatite on bone defect","authors":"Rui Ge, Cong Xun, Jingzhou Yang, Weitao Jia, Yuancheng Li","doi":"10.1088/1748-605X/ab4238","DOIUrl":"https://doi.org/10.1088/1748-605X/ab4238","url":null,"abstract":"The treatment of large-area bone defects is a huge challenge and the current research hot spot is to prepare composite materials to promote the new bone formation. In this study, the rat skull defect was repaired by implanting pure wollastonite and hydroxyapatite composites, which proved that it has a good effect on the treatment of bone defects. 60 SD rats were used as research objects. The animals were randomly divided into wollastonite group, wollastonite-hydroxyapatite composite group and hydroxyapatite group. The three groups of bone scaffolds were filled into the rats’ skull defects. At 6 and 12 weeks after surgery, we conducted Micro-CT analysis, HE staining, Masson trichrome staining, Alizarin red staining and Microfil analysis, to assess the therapeutic and regeneration effects of three groups. At 6 weeks after implantation, the morphology results showed that little newly formed bone was observed in wollastonite group, on the contrary, more new bone in the surgical defects formed in the wollastonite-hydroxyapatite composite group and hydroxyapatite group. At 12 weeks after surgery, histology analyses revealed that the regenerated bone became more mature in each groups. The morphology showed that the maturity of new bone was improved and the scaffold material was partially absorbed in wollastonite-hydroxyapatite composite group. CT scan observation showed that on the coronal plane, the defect repair area of wollastonite-hydroxyapatite composite group was integrated with the surrounding normal bone tissue, and the sacffold material was tightly integrated with the defect edge. The results of Microfil showed that compared with wollastonite group and hydroxyapatite group, wollastonite-hydroxyapatite composite group formed more blood vessels after 12 weeks of surgery. The wollastonite-hydroxyapatite composite biomaterial can promote the formation and growth of new bone in the defect area, and it is considered safe.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2019-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab4238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48850612","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":"Long-term anticoagulation and selective cells adhesion surface via combination of covalent grafting and layer by layer assembly","authors":"Chaojing Li, Jifu Mao, Qiwei Li, Fujun Wang, Yongjie Jiao, Ze Zhang, R. Guidoin, Lu Wang","doi":"10.1088/1748-605X/ab452b","DOIUrl":"https://doi.org/10.1088/1748-605X/ab452b","url":null,"abstract":"Surface modification by long-term active component is essential for biocompatible polymers-based vascular grafts to prevent thrombus formation and reduce intimal hyperplasia. In this study, a simple approach was developed to immobilize bioactive heparin to the surface of ε-polycaprolactone (PCL) grafts through a two-step strategy combining covalent grafting and layer by layer assembly of polyelectrolytes. The performance of heparinized PCL was evaluated in vitro, including the release behavior of heparin, anticoagulation and different types of cells adhesion characteristic. A sustained-release of heparin was achieved by this immobilization strategy. Surface remaining heparin was up to 1.10 μg cm−2 on the modified PCL after release in vitro for 30 d. Specifically, the heparinized PCL has the long-term ability to prevent adhesion of blood cells and thrombus formation, and significantly inhibit the adhesion of smooth muscle cells. The two-step strategy provides a simple and general route to incorporate heparin on PCL graft surface. The surface heparinized PCL demonstrated in this work can be a useful material platform for biodegradable vascular stent graft.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2019-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab452b","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42570561","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":"Scaffold-free bioprinted osteogenic and chondrogenic systems to model osteochondral physiology","authors":"Erick Breathwaite, J. Weaver, Angela C Murchison, Michelle L Treadwell, J. Odanga, Jung Bok Lee","doi":"10.1088/1748-605X/ab4243","DOIUrl":"https://doi.org/10.1088/1748-605X/ab4243","url":null,"abstract":"Three-dimensional bioprinted culture platforms mimic the native microenvironment of tissues more accurately than two-dimensional cell cultures or animal models. Scaffold-free bioprinting eliminates many complications associated with traditional scaffold-dependent printing as well as provides better cell-to-cell interactions and long-term functionality. In this study, constructs were produced from bone marrow derived mesenchymal stem cells (BM-MSCs) using a scaffold-free bioprinter. These constructs were cultured in either osteogenic, chondrogenic, a 50:50 mixture of osteogenic and chondrogenic (‘osteo-chondro’), or BM-MSC growth medium. Osteogenic and chondrogenic differentiation capacity was determined over an 8-week culture period using histological and immunohistochemical staining and RT-qPCR (Phase I). After 6 weeks in culture, individual osteogenic and chondrogenic differentiated constructs were adhered to create a bone-cartilage interaction model. Adhered differentiated constructs were cultured for an additional 8 weeks in either chondrogenic or osteo-chondro medium to evaluate sustainability of lineage specification and transdifferentiation potential (Phase II). Constructs cultured in their respective osteogenic and/or chondrogenic medium differentiated directly into bone (model of intramembranous ossification) or cartilage. Positive histological and immunohistochemical staining for bone or cartilage identification was shown after 4 and 8 weeks in culture. Expression of osteogenesis and chondrogenesis associated genes increased between weeks 2 and 6. Adhered individual osteogenic and chondrogenic differentiated constructs sustained their differentiated phenotype when cultured in chondrogenic medium. However, adhered individual chondrogenic differentiated constructs cultured in osteo-chondro medium were converted to bone (model of metaplastic transformation). These bioprinted models of bone-cartilage interaction, intramembranous ossification, and metaplastic transformation of cartilage into bone offer a useful and promising approach for bone and cartilage tissue engineering research. Specifically, these models can be potentially used as functional tissue systems for studying osteochondral defect repair, drug discovery and response, and many other potential applications.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2019-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab4243","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44938741","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":"3D printing of layered mesoporous bioactive glass/sodium alginate-sodium alginate scaffolds with controllable dual-drug release behaviors","authors":"Shengyang Fu, Xiaoyu Du, Min Zhu, Z. Tian, Daixu Wei, Yufang Zhu","doi":"10.1088/1748-605X/ab4166","DOIUrl":"https://doi.org/10.1088/1748-605X/ab4166","url":null,"abstract":"Scaffolds with controlled drug release are valuable for bone tissue engineering, but constructing the scaffolds with controllable dual-drug release behaviors is still a challenge. In this study, layered mesoporous bioactive glass/sodium alginate-sodium alginate (MBG/SA–SA) scaffolds with controllable dual-drug release behaviors were fabricated by 3D printing. The porosity and compressive strength of three-dimensional (3D) printed MBG/SA–SA scaffolds by cross-linking are about 78% and 4.2 MPa, respectively. As two model drugs, bovine serum albumin (BSA) and ibuprofen (IBU) were separately loaded in SA layer and MBG/SA layer, resulting in a relatively fast release of BSA and a sustained release of IBU. Furthermore, layered MBG/SA–SA scaffolds were able to stimulate human bone mesenchymal stem cells (hBMSCs) adhesion, proliferation and osteogenic differentiation than SA scaffolds. Hence, the 3D printed MBG/SA–SA scaffolds would be prospective for the treatment of bone defects.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2019-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab4166","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46256127","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":"A comparative study on agarose acetate and PDLLA scaffold for rabbit femur defect regeneration","authors":"Ruifang Zhao, Zunkai Xu, Bing Li, Tao Chen, Naibin Mei, Chuang Wang, Zongbao Zhou, Lingling You, Chaoxi Wu, Xiaoying Wang, Shunqing Tang","doi":"10.1088/1748-605X/ab3c1b","DOIUrl":"https://doi.org/10.1088/1748-605X/ab3c1b","url":null,"abstract":"The development of degradable polymer scaffolds is a key issue in bone regeneration. Poly(D, L-lactide) (PDLLA) and its derivatives have usually been applied to the construction of degradable scaffolds, but these scaffolds had problems with acidic degradation products and quick loss of mechanic strength during the later degradation, which usually led to scaffold collapse and cavity formation because of the slower rate of bone regeneration. In the present paper, a polysaccharide derivative, agarose acetate (AGA), was synthesized and a novel porous AGA scaffold was successfully developed through a salt-leaching process. The AGA scaffold had over 90% porosity without swelling in water, and compared to collapse and acidic products of PDLLA scaffold during degradation, the AGA scaffold maintained a stable morphology and a nearly neutral pH value over 18 months’ degradation in PBS. A bone mesenchymal stem cells (BMSCs) adhesion and proliferation experiment showed that more cells adhered to the AGA scaffold than to the PDLLA scaffold. A subcutaneous implant test showed that the AGA scaffold slowly degraded and did not cause an inflammatory response surrounding the implantation lesion site. AGA scaffold was implanted into femur defects in New Zealand white rabbits to test its in vivo performance. Results indicated that the AGA scaffold accelerated the process of bone regeneration compared to the PDLLA group and, with time, new bone was formed from the margin toward the center of the scaffolds, and the scaffold left in place retained its porous structure without collapsing. Meanwhile, the AGA scaffold showed a low degradation rate and kept its shape during the in vivo degradation compared to the PDLLA scaffold. This performance could have the benefit of integrated regenerative bone being formed instead of cavities due to the quickly degraded scaffold disappearing. These results demonstrate that the AGA scaffold has significant potential in bone regeneration applications.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2019-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab3c1b","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47926307","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":"Enhanced osteoblasts adhesion and collagen formation on biomimetic polyvinylidene fluoride (PVDF) films for bone regeneration","authors":"P. Szewczyk, Sara Metwally, Zuzanna J. Krysiak, Łukasz Kaniuk, J. Karbowniczek, U. Stachewicz","doi":"10.1088/1748-605X/ab3c20","DOIUrl":"https://doi.org/10.1088/1748-605X/ab3c20","url":null,"abstract":"Bone tissue engineering can be utilized to study the early events of osteoconduction. Fundamental research in cell adhesion to various geometries and proliferation has shown the potential of extending it to implantable devices for regenerative medicine. Following this concept in our studies, first, we developed well-controlled processing of polyvinylidene fluoride (PVDF) film to obtain a surface biomimicking ECM. We optimized the manufacturing dependent on humidity and temperature during spin-coating of a polymer solution. The mixture of solvents such as dimethylacetamide and acetone together with high humidity conditions led to a biomimetic, highly porous and rough surface, while with lower humidity and high temperatures drying allowed us to obtain a smooth and flat PVDF film. The roughness of the PVDF film was biofabricated and compared to smooth films in cell culture studies for adhesion and proliferation of osteoblasts. The bioinspired roughness of our films enhanced the osteoblast adhesion by over 44%, and there was collagen formation already after 7 days of cell culturing that was proved via scanning electron microscopy observation, light microscopy imaging after Sirius Red staining, and proliferation test such as MTS. Cell development, via extended filopodia, formed profoundly on the rough PVDF surface, demonstrated the potential of the structural design of biomimetic surfaces to enhance further bone tissue regeneration.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":"14 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2019-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab3c20","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60551888","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":"Nanocomposite-coated porous templates for engineered bone scaffolds: a parametric study of layer-by-layer assembly conditions","authors":"M. Ziminska, M. Chalanqui, P. Chambers, J. Acheson, H. McCarthy, N. Dunne, A. Hamilton","doi":"10.1088/1748-605X/ab3b7b","DOIUrl":"https://doi.org/10.1088/1748-605X/ab3b7b","url":null,"abstract":"Using the layer-by-layer (LbL) assembly technique to deposit mechanically reinforcing coatings onto porous templates is a route for fabricating engineered bone scaffold materials with a combination of high porosity, strength, and stiffness. LbL assembly involves the sequential deposition of nano- to micro-scale multilayer coatings from aqueous solutions. Here, a design of experiments (DOE) approach was used to evaluate LbL assembly of polyethyleneimine (PEI), polyacrylic acid (PAA), and nanoclay coatings onto open-cell polyurethane foam templates. The thickness of the coatings, and the porosity, elastic modulus and collapse stress of coated foam templates were most strongly affected by the pH of PAA solutions, salt concentration, and interactions between these factors. The mechanical properties of coated foams correlated with the thickness of the coatings, but were also ascribed to changes in the coating properties due to the different assembly conditions. A DOE optimization aimed to balance the trade-off between higher mechanical properties but lower porosity of foam templates with increasing coating thickness. Micromechanical modeling predicted that deposition of 116 QLs would achieve mechanical properties of cancellous bone (>0.05 GPa stiffness and >2 MPa strength) at a suitable porosity of >70%. When capped with a final layer of PAA and cross-linked via thermal treatment, the PEI/PAA/PEI/nanoclay coatings exhibited good indirect cytotoxicity with mesenchymal stem cells. The ability of LbL assembly to deposit a wide range of functional constituents within multilayer-structured coatings makes the general strategy of templated LbL assembly a powerful route for fabricating engineered tissue scaffolds that can be applied onto various porous template materials to achieve a wide range of properties, pore structures, and multifunctionality.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2019-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab3b7b","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46733930","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":"Poly(D,L-lactide)/PEG blend films for keratinocyte cultivation and skin reconstruction","authors":"Y. Nashchekina, I. Samusenko, I. Zorin, L. Kukhareva, A. Bilibin, M. Blinova","doi":"10.1088/1748-605X/ab3aa2","DOIUrl":"https://doi.org/10.1088/1748-605X/ab3aa2","url":null,"abstract":"The objective of this study was to develop a novel porous thin poly(D,L-lactide) (PLA) film as a tissue-engineering scaffold for keratinocytes used for the replacement of damaged skin. Poly(D,l-lactic acid)/poly(ethylene glycol) (PEG: Mw 6000 or 15 000) blend films were formed by a spin coating technique. The properties and structures of these blend films were investigated. PDLA/PEG (6000) blend films were modified by microfibrillar collagen after water incubation to increase hydrophilicity and improve keratinocyte adhesion. Primary keratinocytes were seeded on PLA films, cultivated for 9 d and transplanted to rats with a model skin defect wound. The wound’s healing after keratinocyte transplantation was assayed with histological and immunochemical methods. It was found that skin damage recovery was the most effective after transplantation of keratinocytes on porous PLA film modified with collagen.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2019-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab3aa2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43024281","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":"Characterization of osteogenic cells grown over modified graphene-oxide-biostable polymers","authors":"E. H. Mirza, A. Khan, A. Al-Khureif, S. Saadaldin, B. A. Mohamed, Fatima Fareedi, Muhammad Muzammil Khan, M. Alfayez, Randa Al-Fotawi, P. Vallittu, Amer Mahmood","doi":"10.1088/1748-605X/ab3ab2","DOIUrl":"https://doi.org/10.1088/1748-605X/ab3ab2","url":null,"abstract":"Graphene is an excellent filler for the development of reinforced composites. This study evaluated bone cement composites of graphene oxide (GO) and poly(methyl methacrylate) (PMMA) based on the proliferation of human bone marrow mesenchymal stem cells (hBMSCs), and the anabolic and catabolic effects of the incorporation of GO on osteoblast cells at a genetic level. Surface wettability and roughness were also evaluated at different GO concentrations (GO1: 0.024 wt% and GO2: 0.048 wt%) in the polymer matrix. Fabricated specimens were tested to (a) observe cell proliferation and (b) identify the effectiveness of GO on the expression of bone morphogenic proteins. Early osteogenesis was observed based on the activity of alkaline phosphatase and the genetic expression of the run-related transcription factor 2. Moreover, bone strengthening was determined by examining the collagen type 1 alpha–1 gene. The surface roughness of the substrate material increased following the addition of GO fillers to the resin matrix. It was found that over a period of ten days, the proliferation of hBMSCs on GO2 was significantly higher compared to the control and GO1. Additionally, quantitative colorimetric mineralization of the extracellular matrix revealed greater calcium phosphate deposition by osteoblasts in GO2. Furthermore, alizarin red staining analysis at day 14 identified the presence of mineralization in the form of dark pigmentation in the central region of GO2. The modified GO–PMMA composite seems to be promising as a bone cement type for the enhancement of the biological activity of bone tissue.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2019-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1088/1748-605X/ab3ab2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43620086","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}