Osteoconductive Amine-Functionalized Graphene–Poly(methyl methacrylate) Bone Cement Composite with Controlled Exothermic Polymerization
Bone cement has found extensive usage in joint arthroplasty over the last 50 years; still, the development of bone cement with essential properties such as high fatigue resistance, lower exothermic temperature, and bioactivity has been an unsolved problem. In our present work, we have addressed all...
Gespeichert in:
Veröffentlicht in: | Bioconjugate chemistry 2017-09, Vol.28 (9), p.2254-2265 |
---|---|
Hauptverfasser: | , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 2265 |
---|---|
container_issue | 9 |
container_start_page | 2254 |
container_title | Bioconjugate chemistry |
container_volume | 28 |
creator | Sharma, Rakesh Kapusetti, Govinda Bhong, Sayali Yashwant Roy, Partha Singh, Santosh Kumar Singh, Shikha Balavigneswaran, Chelladurai Karthikeyan Mahato, Kaushal Kumar Ray, Biswajit Maiti, Pralay Misra, Nira |
description | Bone cement has found extensive usage in joint arthroplasty over the last 50 years; still, the development of bone cement with essential properties such as high fatigue resistance, lower exothermic temperature, and bioactivity has been an unsolved problem. In our present work, we have addressed all of the mentioned shortcomings of bone cement by reinforcing it with graphene (GR), graphene oxide (GO), and surface-modified amino graphene (AG) fillers. These nanocomposites have shown hypsochromic shifts, suggesting strong interactions between the filler material and the polymer matrix. AG-based nanohybrids have shown greater osteointegration and lower cytotoxicity compared to other nanohybrids as well as pristine bone cement. They have also reduced oxidative stress on cells, resulting in calcification within 20 days of the implantation of nanohybrids into the rabbits. They have significantly reduced the exothermic curing temperature to body temperature and increased the setting time to facilitate practitioners, suggesting that reaction temperature and settling time can be dynamically controlled by varying the concentration of the filler. Thermal stability and enhanced mechanical properties have been achieved in nanohybrids vis-à-vis pure bone cement. Thus, this newly developed nanocomposite can create natural bonding with bone tissues for improved bioactivity, longer sustainability, and better strength in the prosthesis. |
doi_str_mv | 10.1021/acs.bioconjchem.7b00241 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1924604580</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1924604580</sourcerecordid><originalsourceid>FETCH-LOGICAL-a385t-f36d3755d35c3a0fa742775b19d531899a5244d68858c4dbdce530e7a46dc2833</originalsourceid><addsrcrecordid>eNqFkU1v1DAQhiMEoqXwFyASl3LI4s_YOZZVW5AqlQOcI8eeVbyy48V2CtsTV878Q34Jjnb5EBdOMyM984w0b1W9wGiFEcGvlU6rwQYdpq0ewa_EgBBh-EF1ijlBDZOYPCw9YrTBEpGT6klKW4RQhyV5XJ0QKTglgp9W325ThsVjZp3tHdQX3k7QXM1TGcOknL0HU19HtRthgh9fv78Pbn_uIY97Vy9F6bh3KsOr-k2YoF6DhynX6-B3IdkM9WebxzJOOQbniuryS8gjRG91vag8RHuvllNPq0cb5RI8O9az6uPV5Yf12-bm9vrd-uKmUVTy3Gxoa6jg3FCuqUIbJRgRgg-4M5xi2XWKE8ZMKyWXmpnBaOAUgVCsNZpISs-q84N3F8OnGVLuvU0anFMThDn1uCOsRYxLVNCX_6DbMMfylIXiLaISS1kocaB0DClF2PS7aL2K-x6jfkmrL2n1f6XVH9Mqm8-P_nnwYH7v_YqnAPQALIY_t_-j_QmFOKpB</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1956038188</pqid></control><display><type>article</type><title>Osteoconductive Amine-Functionalized Graphene–Poly(methyl methacrylate) Bone Cement Composite with Controlled Exothermic Polymerization</title><source>MEDLINE</source><source>American Chemical Society Journals</source><creator>Sharma, Rakesh ; Kapusetti, Govinda ; Bhong, Sayali Yashwant ; Roy, Partha ; Singh, Santosh Kumar ; Singh, Shikha ; Balavigneswaran, Chelladurai Karthikeyan ; Mahato, Kaushal Kumar ; Ray, Biswajit ; Maiti, Pralay ; Misra, Nira</creator><creatorcontrib>Sharma, Rakesh ; Kapusetti, Govinda ; Bhong, Sayali Yashwant ; Roy, Partha ; Singh, Santosh Kumar ; Singh, Shikha ; Balavigneswaran, Chelladurai Karthikeyan ; Mahato, Kaushal Kumar ; Ray, Biswajit ; Maiti, Pralay ; Misra, Nira</creatorcontrib><description>Bone cement has found extensive usage in joint arthroplasty over the last 50 years; still, the development of bone cement with essential properties such as high fatigue resistance, lower exothermic temperature, and bioactivity has been an unsolved problem. In our present work, we have addressed all of the mentioned shortcomings of bone cement by reinforcing it with graphene (GR), graphene oxide (GO), and surface-modified amino graphene (AG) fillers. These nanocomposites have shown hypsochromic shifts, suggesting strong interactions between the filler material and the polymer matrix. AG-based nanohybrids have shown greater osteointegration and lower cytotoxicity compared to other nanohybrids as well as pristine bone cement. They have also reduced oxidative stress on cells, resulting in calcification within 20 days of the implantation of nanohybrids into the rabbits. They have significantly reduced the exothermic curing temperature to body temperature and increased the setting time to facilitate practitioners, suggesting that reaction temperature and settling time can be dynamically controlled by varying the concentration of the filler. Thermal stability and enhanced mechanical properties have been achieved in nanohybrids vis-à-vis pure bone cement. Thus, this newly developed nanocomposite can create natural bonding with bone tissues for improved bioactivity, longer sustainability, and better strength in the prosthesis.</description><identifier>ISSN: 1043-1802</identifier><identifier>EISSN: 1520-4812</identifier><identifier>DOI: 10.1021/acs.bioconjchem.7b00241</identifier><identifier>PMID: 28753275</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Amination ; Animals ; Arthroplasty ; Biocompatibility ; Biological activity ; Biomedical materials ; Body temperature ; Bonding strength ; Bone Cements - chemistry ; Bone implants ; Bone Substitutes - chemistry ; Bones ; Calcification ; Carbon ; Cell Line ; Cement ; Cement reinforcements ; Composite materials ; Control stability ; Curing ; Cytotoxicity ; Dynamic stability ; Exothermic reactions ; Fatigue ; Fatigue strength ; Fillers ; Graphene ; Graphite - chemistry ; Humans ; Implantation ; Materials Testing ; Matrix ; Mechanical properties ; Nanocomposites ; Nanocomposites - chemistry ; Nanocomposites - ultrastructure ; Osseointegration ; Osteoconduction ; Osteogenesis ; Oxidative stress ; Polymerization ; Polymethyl methacrylate ; Polymethyl Methacrylate - chemistry ; Prostheses ; Rabbits ; Surgical implants ; Sustainability ; Temperature ; Temperature effects ; Thermal stability ; Tissues ; Toxicity</subject><ispartof>Bioconjugate chemistry, 2017-09, Vol.28 (9), p.2254-2265</ispartof><rights>Copyright © 2017 American Chemical Society</rights><rights>Copyright American Chemical Society Sep 20, 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a385t-f36d3755d35c3a0fa742775b19d531899a5244d68858c4dbdce530e7a46dc2833</citedby><cites>FETCH-LOGICAL-a385t-f36d3755d35c3a0fa742775b19d531899a5244d68858c4dbdce530e7a46dc2833</cites><orcidid>0000-0002-6879-3591 ; 0000-0002-3700-5206 ; 0000-0001-5858-9004</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.7b00241$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.bioconjchem.7b00241$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28753275$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sharma, Rakesh</creatorcontrib><creatorcontrib>Kapusetti, Govinda</creatorcontrib><creatorcontrib>Bhong, Sayali Yashwant</creatorcontrib><creatorcontrib>Roy, Partha</creatorcontrib><creatorcontrib>Singh, Santosh Kumar</creatorcontrib><creatorcontrib>Singh, Shikha</creatorcontrib><creatorcontrib>Balavigneswaran, Chelladurai Karthikeyan</creatorcontrib><creatorcontrib>Mahato, Kaushal Kumar</creatorcontrib><creatorcontrib>Ray, Biswajit</creatorcontrib><creatorcontrib>Maiti, Pralay</creatorcontrib><creatorcontrib>Misra, Nira</creatorcontrib><title>Osteoconductive Amine-Functionalized Graphene–Poly(methyl methacrylate) Bone Cement Composite with Controlled Exothermic Polymerization</title><title>Bioconjugate chemistry</title><addtitle>Bioconjugate Chem</addtitle><description>Bone cement has found extensive usage in joint arthroplasty over the last 50 years; still, the development of bone cement with essential properties such as high fatigue resistance, lower exothermic temperature, and bioactivity has been an unsolved problem. In our present work, we have addressed all of the mentioned shortcomings of bone cement by reinforcing it with graphene (GR), graphene oxide (GO), and surface-modified amino graphene (AG) fillers. These nanocomposites have shown hypsochromic shifts, suggesting strong interactions between the filler material and the polymer matrix. AG-based nanohybrids have shown greater osteointegration and lower cytotoxicity compared to other nanohybrids as well as pristine bone cement. They have also reduced oxidative stress on cells, resulting in calcification within 20 days of the implantation of nanohybrids into the rabbits. They have significantly reduced the exothermic curing temperature to body temperature and increased the setting time to facilitate practitioners, suggesting that reaction temperature and settling time can be dynamically controlled by varying the concentration of the filler. Thermal stability and enhanced mechanical properties have been achieved in nanohybrids vis-à-vis pure bone cement. Thus, this newly developed nanocomposite can create natural bonding with bone tissues for improved bioactivity, longer sustainability, and better strength in the prosthesis.</description><subject>Amination</subject><subject>Animals</subject><subject>Arthroplasty</subject><subject>Biocompatibility</subject><subject>Biological activity</subject><subject>Biomedical materials</subject><subject>Body temperature</subject><subject>Bonding strength</subject><subject>Bone Cements - chemistry</subject><subject>Bone implants</subject><subject>Bone Substitutes - chemistry</subject><subject>Bones</subject><subject>Calcification</subject><subject>Carbon</subject><subject>Cell Line</subject><subject>Cement</subject><subject>Cement reinforcements</subject><subject>Composite materials</subject><subject>Control stability</subject><subject>Curing</subject><subject>Cytotoxicity</subject><subject>Dynamic stability</subject><subject>Exothermic reactions</subject><subject>Fatigue</subject><subject>Fatigue strength</subject><subject>Fillers</subject><subject>Graphene</subject><subject>Graphite - chemistry</subject><subject>Humans</subject><subject>Implantation</subject><subject>Materials Testing</subject><subject>Matrix</subject><subject>Mechanical properties</subject><subject>Nanocomposites</subject><subject>Nanocomposites - chemistry</subject><subject>Nanocomposites - ultrastructure</subject><subject>Osseointegration</subject><subject>Osteoconduction</subject><subject>Osteogenesis</subject><subject>Oxidative stress</subject><subject>Polymerization</subject><subject>Polymethyl methacrylate</subject><subject>Polymethyl Methacrylate - chemistry</subject><subject>Prostheses</subject><subject>Rabbits</subject><subject>Surgical implants</subject><subject>Sustainability</subject><subject>Temperature</subject><subject>Temperature effects</subject><subject>Thermal stability</subject><subject>Tissues</subject><subject>Toxicity</subject><issn>1043-1802</issn><issn>1520-4812</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhiMEoqXwFyASl3LI4s_YOZZVW5AqlQOcI8eeVbyy48V2CtsTV878Q34Jjnb5EBdOMyM984w0b1W9wGiFEcGvlU6rwQYdpq0ewa_EgBBh-EF1ijlBDZOYPCw9YrTBEpGT6klKW4RQhyV5XJ0QKTglgp9W325ThsVjZp3tHdQX3k7QXM1TGcOknL0HU19HtRthgh9fv78Pbn_uIY97Vy9F6bh3KsOr-k2YoF6DhynX6-B3IdkM9WebxzJOOQbniuryS8gjRG91vag8RHuvllNPq0cb5RI8O9az6uPV5Yf12-bm9vrd-uKmUVTy3Gxoa6jg3FCuqUIbJRgRgg-4M5xi2XWKE8ZMKyWXmpnBaOAUgVCsNZpISs-q84N3F8OnGVLuvU0anFMThDn1uCOsRYxLVNCX_6DbMMfylIXiLaISS1kocaB0DClF2PS7aL2K-x6jfkmrL2n1f6XVH9Mqm8-P_nnwYH7v_YqnAPQALIY_t_-j_QmFOKpB</recordid><startdate>20170920</startdate><enddate>20170920</enddate><creator>Sharma, Rakesh</creator><creator>Kapusetti, Govinda</creator><creator>Bhong, Sayali Yashwant</creator><creator>Roy, Partha</creator><creator>Singh, Santosh Kumar</creator><creator>Singh, Shikha</creator><creator>Balavigneswaran, Chelladurai Karthikeyan</creator><creator>Mahato, Kaushal Kumar</creator><creator>Ray, Biswajit</creator><creator>Maiti, Pralay</creator><creator>Misra, Nira</creator><general>American Chemical Society</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>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6879-3591</orcidid><orcidid>https://orcid.org/0000-0002-3700-5206</orcidid><orcidid>https://orcid.org/0000-0001-5858-9004</orcidid></search><sort><creationdate>20170920</creationdate><title>Osteoconductive Amine-Functionalized Graphene–Poly(methyl methacrylate) Bone Cement Composite with Controlled Exothermic Polymerization</title><author>Sharma, Rakesh ; Kapusetti, Govinda ; Bhong, Sayali Yashwant ; Roy, Partha ; Singh, Santosh Kumar ; Singh, Shikha ; Balavigneswaran, Chelladurai Karthikeyan ; Mahato, Kaushal Kumar ; Ray, Biswajit ; Maiti, Pralay ; Misra, Nira</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a385t-f36d3755d35c3a0fa742775b19d531899a5244d68858c4dbdce530e7a46dc2833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Amination</topic><topic>Animals</topic><topic>Arthroplasty</topic><topic>Biocompatibility</topic><topic>Biological activity</topic><topic>Biomedical materials</topic><topic>Body temperature</topic><topic>Bonding strength</topic><topic>Bone Cements - chemistry</topic><topic>Bone implants</topic><topic>Bone Substitutes - chemistry</topic><topic>Bones</topic><topic>Calcification</topic><topic>Carbon</topic><topic>Cell Line</topic><topic>Cement</topic><topic>Cement reinforcements</topic><topic>Composite materials</topic><topic>Control stability</topic><topic>Curing</topic><topic>Cytotoxicity</topic><topic>Dynamic stability</topic><topic>Exothermic reactions</topic><topic>Fatigue</topic><topic>Fatigue strength</topic><topic>Fillers</topic><topic>Graphene</topic><topic>Graphite - chemistry</topic><topic>Humans</topic><topic>Implantation</topic><topic>Materials Testing</topic><topic>Matrix</topic><topic>Mechanical properties</topic><topic>Nanocomposites</topic><topic>Nanocomposites - chemistry</topic><topic>Nanocomposites - ultrastructure</topic><topic>Osseointegration</topic><topic>Osteoconduction</topic><topic>Osteogenesis</topic><topic>Oxidative stress</topic><topic>Polymerization</topic><topic>Polymethyl methacrylate</topic><topic>Polymethyl Methacrylate - chemistry</topic><topic>Prostheses</topic><topic>Rabbits</topic><topic>Surgical implants</topic><topic>Sustainability</topic><topic>Temperature</topic><topic>Temperature effects</topic><topic>Thermal stability</topic><topic>Tissues</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sharma, Rakesh</creatorcontrib><creatorcontrib>Kapusetti, Govinda</creatorcontrib><creatorcontrib>Bhong, Sayali Yashwant</creatorcontrib><creatorcontrib>Roy, Partha</creatorcontrib><creatorcontrib>Singh, Santosh Kumar</creatorcontrib><creatorcontrib>Singh, Shikha</creatorcontrib><creatorcontrib>Balavigneswaran, Chelladurai Karthikeyan</creatorcontrib><creatorcontrib>Mahato, Kaushal Kumar</creatorcontrib><creatorcontrib>Ray, Biswajit</creatorcontrib><creatorcontrib>Maiti, Pralay</creatorcontrib><creatorcontrib>Misra, Nira</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Bioconjugate chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sharma, Rakesh</au><au>Kapusetti, Govinda</au><au>Bhong, Sayali Yashwant</au><au>Roy, Partha</au><au>Singh, Santosh Kumar</au><au>Singh, Shikha</au><au>Balavigneswaran, Chelladurai Karthikeyan</au><au>Mahato, Kaushal Kumar</au><au>Ray, Biswajit</au><au>Maiti, Pralay</au><au>Misra, Nira</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Osteoconductive Amine-Functionalized Graphene–Poly(methyl methacrylate) Bone Cement Composite with Controlled Exothermic Polymerization</atitle><jtitle>Bioconjugate chemistry</jtitle><addtitle>Bioconjugate Chem</addtitle><date>2017-09-20</date><risdate>2017</risdate><volume>28</volume><issue>9</issue><spage>2254</spage><epage>2265</epage><pages>2254-2265</pages><issn>1043-1802</issn><eissn>1520-4812</eissn><abstract>Bone cement has found extensive usage in joint arthroplasty over the last 50 years; still, the development of bone cement with essential properties such as high fatigue resistance, lower exothermic temperature, and bioactivity has been an unsolved problem. In our present work, we have addressed all of the mentioned shortcomings of bone cement by reinforcing it with graphene (GR), graphene oxide (GO), and surface-modified amino graphene (AG) fillers. These nanocomposites have shown hypsochromic shifts, suggesting strong interactions between the filler material and the polymer matrix. AG-based nanohybrids have shown greater osteointegration and lower cytotoxicity compared to other nanohybrids as well as pristine bone cement. They have also reduced oxidative stress on cells, resulting in calcification within 20 days of the implantation of nanohybrids into the rabbits. They have significantly reduced the exothermic curing temperature to body temperature and increased the setting time to facilitate practitioners, suggesting that reaction temperature and settling time can be dynamically controlled by varying the concentration of the filler. Thermal stability and enhanced mechanical properties have been achieved in nanohybrids vis-à-vis pure bone cement. Thus, this newly developed nanocomposite can create natural bonding with bone tissues for improved bioactivity, longer sustainability, and better strength in the prosthesis.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>28753275</pmid><doi>10.1021/acs.bioconjchem.7b00241</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-6879-3591</orcidid><orcidid>https://orcid.org/0000-0002-3700-5206</orcidid><orcidid>https://orcid.org/0000-0001-5858-9004</orcidid></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1043-1802 |
ispartof | Bioconjugate chemistry, 2017-09, Vol.28 (9), p.2254-2265 |
issn | 1043-1802 1520-4812 |
language | eng |
recordid | cdi_proquest_miscellaneous_1924604580 |
source | MEDLINE; American Chemical Society Journals |
subjects | Amination Animals Arthroplasty Biocompatibility Biological activity Biomedical materials Body temperature Bonding strength Bone Cements - chemistry Bone implants Bone Substitutes - chemistry Bones Calcification Carbon Cell Line Cement Cement reinforcements Composite materials Control stability Curing Cytotoxicity Dynamic stability Exothermic reactions Fatigue Fatigue strength Fillers Graphene Graphite - chemistry Humans Implantation Materials Testing Matrix Mechanical properties Nanocomposites Nanocomposites - chemistry Nanocomposites - ultrastructure Osseointegration Osteoconduction Osteogenesis Oxidative stress Polymerization Polymethyl methacrylate Polymethyl Methacrylate - chemistry Prostheses Rabbits Surgical implants Sustainability Temperature Temperature effects Thermal stability Tissues Toxicity |
title | Osteoconductive Amine-Functionalized Graphene–Poly(methyl methacrylate) Bone Cement Composite with Controlled Exothermic Polymerization |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T02%3A15%3A18IST&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=Osteoconductive%20Amine-Functionalized%20Graphene%E2%80%93Poly(methyl%20methacrylate)%20Bone%20Cement%20Composite%20with%20Controlled%20Exothermic%20Polymerization&rft.jtitle=Bioconjugate%20chemistry&rft.au=Sharma,%20Rakesh&rft.date=2017-09-20&rft.volume=28&rft.issue=9&rft.spage=2254&rft.epage=2265&rft.pages=2254-2265&rft.issn=1043-1802&rft.eissn=1520-4812&rft_id=info:doi/10.1021/acs.bioconjchem.7b00241&rft_dat=%3Cproquest_cross%3E1924604580%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=1956038188&rft_id=info:pmid/28753275&rfr_iscdi=true |