Studies on effect of CuO addition on mechanical properties and in vitro cytocompatibility in 1393 bioactive glass scaffold
Copper doped bioactive glasses have been reported as the potential biomaterial for diseased or damaged bone repair and act as stimulants to new bones formation. In the present manuscript, we have synthesized 1393 derived glass based scaffold with the general formula of (54.6 − X)SiO2·6Na2O·7.9 K2O·7...
Gespeichert in:
Veröffentlicht in: | Materials Science & Engineering C 2018-12, Vol.93, p.341-355 |
---|---|
Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 355 |
---|---|
container_issue | |
container_start_page | 341 |
container_title | Materials Science & Engineering C |
container_volume | 93 |
creator | Ali, Akher Ershad, Md Vyas, Vikash Kumar Hira, Sumit Kumar Manna, Partha Pratim Singh, B.N. Yadav, Shushma Srivastava, P. Singh, S.P. Pyare, Ram |
description | Copper doped bioactive glasses have been reported as the potential biomaterial for diseased or damaged bone repair and act as stimulants to new bones formation. In the present manuscript, we have synthesized 1393 derived glass based scaffold with the general formula of (54.6 − X)SiO2·6Na2O·7.9 K2O·7.7 MgO·22 CaO·1.74 P2O5·XCuO (all are in mole%; where X = 0,1,2,3) through traditional melt-quench route and the samples were designated as 1393, 1393-1Cu, 1393-2Cu and 1393-3Cu respectively. Polymer foam with interconnected pores has been used on later stage to prepare porous (porosity > 50%) bioactive scaffolds. The addition of CuO in glass scaffolds was to ensure its cytocompatibility, ability to enhance cell proliferation and improvements in mechanical properties. Increasing trend of CuO in the 1393 glass scaffold has resulted in increasing compressive and flexural strength and elastic modulus of the scaffolds.
In-vitro cellular growth inhibition and cell viability assay of CuO incorporated 1393 glass scaffolds demonstrated that it did not inhibit proliferation and viability of human squamous carcinoma cell (SCC-25) at low materials concentration. The materials caused moderate level of apoptosis at higher concentrations and were also tolerated by human RBC as studied by hemolytic assay. The results indicated that CuO incorporated 1393 scaffolds could be a potential biomaterial for neobone tissue engineering application.
•CuO incorporated 1393 scaffolds having ̴ 70% porosity could be a potential biomaterial for bone tissue ingrowth.•Modification of 1393 scaffold via doping with CuO enhances physico-chemical and mechanical properties.•1393 derived scaffolds show optimal cytocompatibility, thus could be considered as neo bone tissue regenerative materials. |
doi_str_mv | 10.1016/j.msec.2018.08.003 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2115754197</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0928493117344004</els_id><sourcerecordid>2129519273</sourcerecordid><originalsourceid>FETCH-LOGICAL-c421t-7ece3565b157282933b89d900362f42f785925eec01e3624bea7815232f2f7f43</originalsourceid><addsrcrecordid>eNp9kU9r3DAQxUVpaDZpv0APRdBLL97oj21ZkEtZ0iQQyCHJWcjSqNViW1tJXth8-shsmkMPgQeCmd88ZvQQ-krJmhLaXmzXYwKzZoR2a1JE-Ae0op3gFaGSfkQrIllX1ZLTU3SW0paQtuOCfUKnnDBRk7ZdoeeHPFsPCYcJg3NgMg4Ob-Z7rK312Zdy0Qjmj5680QPexbCDmJcRPVnsJ7z3OQZsDjmYMO509r0ffD4sLcolx70P2mS_B_x70CnhZLRzYbCf0YnTQ4Ivr-85evp19bi5qe7ur283P-8qUzOaKwEGeNM2PW0E65jkvO-kleXalrmaOdE1kjUAhlAopboHLTraMM5cabqan6MfR9-y-t8ZUlajTwaGQU8Q5qQYLc5NTaUo6Pf_0G2Y41S2KxSTDZVM8EKxI2ViSCmCU7voRx0PihK1JKO2aklGLckoUkSWoW-v1nM_gn0b-RdFAS6PAJS_2HuIKhkPkwHrY4lF2eDf838B-7qeTA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2129519273</pqid></control><display><type>article</type><title>Studies on effect of CuO addition on mechanical properties and in vitro cytocompatibility in 1393 bioactive glass scaffold</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Ali, Akher ; Ershad, Md ; Vyas, Vikash Kumar ; Hira, Sumit Kumar ; Manna, Partha Pratim ; Singh, B.N. ; Yadav, Shushma ; Srivastava, P. ; Singh, S.P. ; Pyare, Ram</creator><creatorcontrib>Ali, Akher ; Ershad, Md ; Vyas, Vikash Kumar ; Hira, Sumit Kumar ; Manna, Partha Pratim ; Singh, B.N. ; Yadav, Shushma ; Srivastava, P. ; Singh, S.P. ; Pyare, Ram</creatorcontrib><description>Copper doped bioactive glasses have been reported as the potential biomaterial for diseased or damaged bone repair and act as stimulants to new bones formation. In the present manuscript, we have synthesized 1393 derived glass based scaffold with the general formula of (54.6 − X)SiO2·6Na2O·7.9 K2O·7.7 MgO·22 CaO·1.74 P2O5·XCuO (all are in mole%; where X = 0,1,2,3) through traditional melt-quench route and the samples were designated as 1393, 1393-1Cu, 1393-2Cu and 1393-3Cu respectively. Polymer foam with interconnected pores has been used on later stage to prepare porous (porosity > 50%) bioactive scaffolds. The addition of CuO in glass scaffolds was to ensure its cytocompatibility, ability to enhance cell proliferation and improvements in mechanical properties. Increasing trend of CuO in the 1393 glass scaffold has resulted in increasing compressive and flexural strength and elastic modulus of the scaffolds.
In-vitro cellular growth inhibition and cell viability assay of CuO incorporated 1393 glass scaffolds demonstrated that it did not inhibit proliferation and viability of human squamous carcinoma cell (SCC-25) at low materials concentration. The materials caused moderate level of apoptosis at higher concentrations and were also tolerated by human RBC as studied by hemolytic assay. The results indicated that CuO incorporated 1393 scaffolds could be a potential biomaterial for neobone tissue engineering application.
•CuO incorporated 1393 scaffolds having ̴ 70% porosity could be a potential biomaterial for bone tissue ingrowth.•Modification of 1393 scaffold via doping with CuO enhances physico-chemical and mechanical properties.•1393 derived scaffolds show optimal cytocompatibility, thus could be considered as neo bone tissue regenerative materials.</description><identifier>ISSN: 0928-4931</identifier><identifier>EISSN: 1873-0191</identifier><identifier>DOI: 10.1016/j.msec.2018.08.003</identifier><identifier>PMID: 30274066</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Apoptosis ; Biocompatibility ; Bioglass ; Biological activity ; Biomaterials ; Biomedical materials ; Bone healing ; Bones ; Cell culture ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Compressive strength ; Copper ; Copper - chemistry ; Copper oxides ; Cytocompatibility ; Glass - chemistry ; Humans ; Materials science ; Materials Testing ; Mechanical properties ; Modulus of elasticity ; Oxides ; Phosphorus pentoxide ; Porosity ; Scaffold ; Scaffolds ; Silicon dioxide ; Stimulants ; Tissue Engineering ; Tissue Scaffolds - chemistry</subject><ispartof>Materials Science & Engineering C, 2018-12, Vol.93, p.341-355</ispartof><rights>2018 Elsevier B.V.</rights><rights>Copyright © 2018 Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier BV Dec 1, 2018</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-7ece3565b157282933b89d900362f42f785925eec01e3624bea7815232f2f7f43</citedby><cites>FETCH-LOGICAL-c421t-7ece3565b157282933b89d900362f42f785925eec01e3624bea7815232f2f7f43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0928493117344004$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30274066$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ali, Akher</creatorcontrib><creatorcontrib>Ershad, Md</creatorcontrib><creatorcontrib>Vyas, Vikash Kumar</creatorcontrib><creatorcontrib>Hira, Sumit Kumar</creatorcontrib><creatorcontrib>Manna, Partha Pratim</creatorcontrib><creatorcontrib>Singh, B.N.</creatorcontrib><creatorcontrib>Yadav, Shushma</creatorcontrib><creatorcontrib>Srivastava, P.</creatorcontrib><creatorcontrib>Singh, S.P.</creatorcontrib><creatorcontrib>Pyare, Ram</creatorcontrib><title>Studies on effect of CuO addition on mechanical properties and in vitro cytocompatibility in 1393 bioactive glass scaffold</title><title>Materials Science & Engineering C</title><addtitle>Mater Sci Eng C Mater Biol Appl</addtitle><description>Copper doped bioactive glasses have been reported as the potential biomaterial for diseased or damaged bone repair and act as stimulants to new bones formation. In the present manuscript, we have synthesized 1393 derived glass based scaffold with the general formula of (54.6 − X)SiO2·6Na2O·7.9 K2O·7.7 MgO·22 CaO·1.74 P2O5·XCuO (all are in mole%; where X = 0,1,2,3) through traditional melt-quench route and the samples were designated as 1393, 1393-1Cu, 1393-2Cu and 1393-3Cu respectively. Polymer foam with interconnected pores has been used on later stage to prepare porous (porosity > 50%) bioactive scaffolds. The addition of CuO in glass scaffolds was to ensure its cytocompatibility, ability to enhance cell proliferation and improvements in mechanical properties. Increasing trend of CuO in the 1393 glass scaffold has resulted in increasing compressive and flexural strength and elastic modulus of the scaffolds.
In-vitro cellular growth inhibition and cell viability assay of CuO incorporated 1393 glass scaffolds demonstrated that it did not inhibit proliferation and viability of human squamous carcinoma cell (SCC-25) at low materials concentration. The materials caused moderate level of apoptosis at higher concentrations and were also tolerated by human RBC as studied by hemolytic assay. The results indicated that CuO incorporated 1393 scaffolds could be a potential biomaterial for neobone tissue engineering application.
•CuO incorporated 1393 scaffolds having ̴ 70% porosity could be a potential biomaterial for bone tissue ingrowth.•Modification of 1393 scaffold via doping with CuO enhances physico-chemical and mechanical properties.•1393 derived scaffolds show optimal cytocompatibility, thus could be considered as neo bone tissue regenerative materials.</description><subject>Apoptosis</subject><subject>Biocompatibility</subject><subject>Bioglass</subject><subject>Biological activity</subject><subject>Biomaterials</subject><subject>Biomedical materials</subject><subject>Bone healing</subject><subject>Bones</subject><subject>Cell culture</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cell Survival</subject><subject>Compressive strength</subject><subject>Copper</subject><subject>Copper - chemistry</subject><subject>Copper oxides</subject><subject>Cytocompatibility</subject><subject>Glass - chemistry</subject><subject>Humans</subject><subject>Materials science</subject><subject>Materials Testing</subject><subject>Mechanical properties</subject><subject>Modulus of elasticity</subject><subject>Oxides</subject><subject>Phosphorus pentoxide</subject><subject>Porosity</subject><subject>Scaffold</subject><subject>Scaffolds</subject><subject>Silicon dioxide</subject><subject>Stimulants</subject><subject>Tissue Engineering</subject><subject>Tissue Scaffolds - chemistry</subject><issn>0928-4931</issn><issn>1873-0191</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU9r3DAQxUVpaDZpv0APRdBLL97oj21ZkEtZ0iQQyCHJWcjSqNViW1tJXth8-shsmkMPgQeCmd88ZvQQ-krJmhLaXmzXYwKzZoR2a1JE-Ae0op3gFaGSfkQrIllX1ZLTU3SW0paQtuOCfUKnnDBRk7ZdoeeHPFsPCYcJg3NgMg4Ob-Z7rK312Zdy0Qjmj5680QPexbCDmJcRPVnsJ7z3OQZsDjmYMO509r0ffD4sLcolx70P2mS_B_x70CnhZLRzYbCf0YnTQ4Ivr-85evp19bi5qe7ur283P-8qUzOaKwEGeNM2PW0E65jkvO-kleXalrmaOdE1kjUAhlAopboHLTraMM5cabqan6MfR9-y-t8ZUlajTwaGQU8Q5qQYLc5NTaUo6Pf_0G2Y41S2KxSTDZVM8EKxI2ViSCmCU7voRx0PihK1JKO2aklGLckoUkSWoW-v1nM_gn0b-RdFAS6PAJS_2HuIKhkPkwHrY4lF2eDf838B-7qeTA</recordid><startdate>20181201</startdate><enddate>20181201</enddate><creator>Ali, Akher</creator><creator>Ershad, Md</creator><creator>Vyas, Vikash Kumar</creator><creator>Hira, Sumit Kumar</creator><creator>Manna, Partha Pratim</creator><creator>Singh, B.N.</creator><creator>Yadav, Shushma</creator><creator>Srivastava, P.</creator><creator>Singh, S.P.</creator><creator>Pyare, Ram</creator><general>Elsevier B.V</general><general>Elsevier BV</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20181201</creationdate><title>Studies on effect of CuO addition on mechanical properties and in vitro cytocompatibility in 1393 bioactive glass scaffold</title><author>Ali, Akher ; Ershad, Md ; Vyas, Vikash Kumar ; Hira, Sumit Kumar ; Manna, Partha Pratim ; Singh, B.N. ; Yadav, Shushma ; Srivastava, P. ; Singh, S.P. ; Pyare, Ram</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-7ece3565b157282933b89d900362f42f785925eec01e3624bea7815232f2f7f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Apoptosis</topic><topic>Biocompatibility</topic><topic>Bioglass</topic><topic>Biological activity</topic><topic>Biomaterials</topic><topic>Biomedical materials</topic><topic>Bone healing</topic><topic>Bones</topic><topic>Cell culture</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Cell Survival</topic><topic>Compressive strength</topic><topic>Copper</topic><topic>Copper - chemistry</topic><topic>Copper oxides</topic><topic>Cytocompatibility</topic><topic>Glass - chemistry</topic><topic>Humans</topic><topic>Materials science</topic><topic>Materials Testing</topic><topic>Mechanical properties</topic><topic>Modulus of elasticity</topic><topic>Oxides</topic><topic>Phosphorus pentoxide</topic><topic>Porosity</topic><topic>Scaffold</topic><topic>Scaffolds</topic><topic>Silicon dioxide</topic><topic>Stimulants</topic><topic>Tissue Engineering</topic><topic>Tissue Scaffolds - chemistry</topic><toplevel>online_resources</toplevel><creatorcontrib>Ali, Akher</creatorcontrib><creatorcontrib>Ershad, Md</creatorcontrib><creatorcontrib>Vyas, Vikash Kumar</creatorcontrib><creatorcontrib>Hira, Sumit Kumar</creatorcontrib><creatorcontrib>Manna, Partha Pratim</creatorcontrib><creatorcontrib>Singh, B.N.</creatorcontrib><creatorcontrib>Yadav, Shushma</creatorcontrib><creatorcontrib>Srivastava, P.</creatorcontrib><creatorcontrib>Singh, S.P.</creatorcontrib><creatorcontrib>Pyare, Ram</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Materials Science & Engineering C</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ali, Akher</au><au>Ershad, Md</au><au>Vyas, Vikash Kumar</au><au>Hira, Sumit Kumar</au><au>Manna, Partha Pratim</au><au>Singh, B.N.</au><au>Yadav, Shushma</au><au>Srivastava, P.</au><au>Singh, S.P.</au><au>Pyare, Ram</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Studies on effect of CuO addition on mechanical properties and in vitro cytocompatibility in 1393 bioactive glass scaffold</atitle><jtitle>Materials Science & Engineering C</jtitle><addtitle>Mater Sci Eng C Mater Biol Appl</addtitle><date>2018-12-01</date><risdate>2018</risdate><volume>93</volume><spage>341</spage><epage>355</epage><pages>341-355</pages><issn>0928-4931</issn><eissn>1873-0191</eissn><abstract>Copper doped bioactive glasses have been reported as the potential biomaterial for diseased or damaged bone repair and act as stimulants to new bones formation. In the present manuscript, we have synthesized 1393 derived glass based scaffold with the general formula of (54.6 − X)SiO2·6Na2O·7.9 K2O·7.7 MgO·22 CaO·1.74 P2O5·XCuO (all are in mole%; where X = 0,1,2,3) through traditional melt-quench route and the samples were designated as 1393, 1393-1Cu, 1393-2Cu and 1393-3Cu respectively. Polymer foam with interconnected pores has been used on later stage to prepare porous (porosity > 50%) bioactive scaffolds. The addition of CuO in glass scaffolds was to ensure its cytocompatibility, ability to enhance cell proliferation and improvements in mechanical properties. Increasing trend of CuO in the 1393 glass scaffold has resulted in increasing compressive and flexural strength and elastic modulus of the scaffolds.
In-vitro cellular growth inhibition and cell viability assay of CuO incorporated 1393 glass scaffolds demonstrated that it did not inhibit proliferation and viability of human squamous carcinoma cell (SCC-25) at low materials concentration. The materials caused moderate level of apoptosis at higher concentrations and were also tolerated by human RBC as studied by hemolytic assay. The results indicated that CuO incorporated 1393 scaffolds could be a potential biomaterial for neobone tissue engineering application.
•CuO incorporated 1393 scaffolds having ̴ 70% porosity could be a potential biomaterial for bone tissue ingrowth.•Modification of 1393 scaffold via doping with CuO enhances physico-chemical and mechanical properties.•1393 derived scaffolds show optimal cytocompatibility, thus could be considered as neo bone tissue regenerative materials.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>30274066</pmid><doi>10.1016/j.msec.2018.08.003</doi><tpages>15</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0928-4931 |
ispartof | Materials Science & Engineering C, 2018-12, Vol.93, p.341-355 |
issn | 0928-4931 1873-0191 |
language | eng |
recordid | cdi_proquest_miscellaneous_2115754197 |
source | MEDLINE; Elsevier ScienceDirect Journals |
subjects | Apoptosis Biocompatibility Bioglass Biological activity Biomaterials Biomedical materials Bone healing Bones Cell culture Cell Line, Tumor Cell Proliferation Cell Survival Compressive strength Copper Copper - chemistry Copper oxides Cytocompatibility Glass - chemistry Humans Materials science Materials Testing Mechanical properties Modulus of elasticity Oxides Phosphorus pentoxide Porosity Scaffold Scaffolds Silicon dioxide Stimulants Tissue Engineering Tissue Scaffolds - chemistry |
title | Studies on effect of CuO addition on mechanical properties and in vitro cytocompatibility in 1393 bioactive glass scaffold |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T00%3A19%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Studies%20on%20effect%20of%20CuO%20addition%20on%20mechanical%20properties%20and%20in%20vitro%20cytocompatibility%20in%201393%20bioactive%20glass%20scaffold&rft.jtitle=Materials%20Science%20&%20Engineering%20C&rft.au=Ali,%20Akher&rft.date=2018-12-01&rft.volume=93&rft.spage=341&rft.epage=355&rft.pages=341-355&rft.issn=0928-4931&rft.eissn=1873-0191&rft_id=info:doi/10.1016/j.msec.2018.08.003&rft_dat=%3Cproquest_cross%3E2129519273%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2129519273&rft_id=info:pmid/30274066&rft_els_id=S0928493117344004&rfr_iscdi=true |