3D Plotted Biphasic Bone Scaffolds for Growth Factor Delivery: Biological Characterization In Vitro and In Vivo
Bioprinting enables the integration of biological components into scaffolds during fabrication that has the advantage of high loading efficiency and better control of release and/or spatial positioning. In this study, a biphasic scaffold fabricated by extrusion‐based 3D multichannel plotting of a ca...
Gespeichert in:
| Veröffentlicht in: | Advanced healthcare materials 2019-04, Vol.8 (7), p.e1801512-n/a |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | n/a |
|---|---|
| container_issue | 7 |
| container_start_page | e1801512 |
| container_title | Advanced healthcare materials |
| container_volume | 8 |
| creator | Ahlfeld, Tilman Schuster, Felix Paul Förster, Yvonne Quade, Mandy Akkineni, Ashwini Rahul Rentsch, Claudia Rammelt, Stefan Gelinsky, Michael Lode, Anja |
| description | Bioprinting enables the integration of biological components into scaffolds during fabrication that has the advantage of high loading efficiency and better control of release and/or spatial positioning. In this study, a biphasic scaffold fabricated by extrusion‐based 3D multichannel plotting of a calcium phosphate cement (CPC) paste and an alginate/gellan gum (AlgGG) hydrogel paste laden with the angiogenic factor VEGF (vascular endothelial growth factor) is investigated with regard to biological response in vitro and in vivo. Rat mesenchymal stromal cells are able to adhere and grow on both CPC and AlgGG strands, and differentiate toward osteoblasts. A sustained VEGF release is observed, which is able to stimulate endothelial cell proliferation as well as angiogenesis in vitro that indicates maintenance of its biological activity. After implantation into a segmental bone defect in the femur diaphysis of rats, a clear reduction of the defect size by newly formed bone tissue occurs from the distal and proximal ends of the host bone within 12 weeks. The CPC component shows excellent osteoconductivity whereas the local VEGF release from the AlgGG hydrogel gives rise to an enhanced vascularization of the defect region. This work contributes to the development of novel therapeutic concepts for improved bone regeneration which are based on 3D bioprinting.
3D extrusion‐based bioprinting is a promising method to fabricate precisely fitting implants containing biological factors for bone regeneration. Herein, hybrid scaffolds consisting of a calcium phosphate cement (CPC) and a biomaterial ink laden with a pro‐angiogenic growth factor are fabricated and investigated in vitro and in vivo. The results show biocompatibility, new bone formation along CPC, and improved vascularization of the scaffolds. |
| doi_str_mv | 10.1002/adhm.201801512 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2188587288</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2206256089</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4102-9d1841d69c727b90d14c93a17b9dd8dd1564bfa96c5dd3039848163d081394b53</originalsourceid><addsrcrecordid>eNqFkU1PIzEMhiO0CBBw5YgicdlLS5zMZJK9QcuXBAKJj2uUJpltUDopyRRUfj1BhSLtZX2xLT9-ZflF6ADIEAihx9pOZ0NKQBCogW6gHQqSDiiv5a91XZFttJ_zMynBa-ACttA2I4KJphE7KLIxvgux753Fp34-1dkbfBo7h--NbtsYbMZtTPgixbd-is-16Us3dsG_urT8U3ZiiH-90QGPpjqVsUv-Xfc-dviqw0--TxHrzq6a17iHNlsdstv_yrvo8fzsYXQ5uL69uBqdXA9MBYQOpAVRgeXSNLSZSGKhMpJpKLW1wlqoeTVpteSmtpYRJkUlgDNLBDBZTWq2i36vdOcpvixc7tXMZ-NC0J2Li6woCFGLhgpR0KN_0Oe4SF25TlFKOK05EbJQwxVlUsw5uVbNk5_ptFRA1Kcb6tMNtXajLBx-yS4mM2fX-PfvCyBXwJsPbvkfOXUyvrz5Ef8Ahy-UAg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2206256089</pqid></control><display><type>article</type><title>3D Plotted Biphasic Bone Scaffolds for Growth Factor Delivery: Biological Characterization In Vitro and In Vivo</title><source>Wiley Online Library Journals Frontfile Complete</source><creator>Ahlfeld, Tilman ; Schuster, Felix Paul ; Förster, Yvonne ; Quade, Mandy ; Akkineni, Ashwini Rahul ; Rentsch, Claudia ; Rammelt, Stefan ; Gelinsky, Michael ; Lode, Anja</creator><creatorcontrib>Ahlfeld, Tilman ; Schuster, Felix Paul ; Förster, Yvonne ; Quade, Mandy ; Akkineni, Ashwini Rahul ; Rentsch, Claudia ; Rammelt, Stefan ; Gelinsky, Michael ; Lode, Anja</creatorcontrib><description>Bioprinting enables the integration of biological components into scaffolds during fabrication that has the advantage of high loading efficiency and better control of release and/or spatial positioning. In this study, a biphasic scaffold fabricated by extrusion‐based 3D multichannel plotting of a calcium phosphate cement (CPC) paste and an alginate/gellan gum (AlgGG) hydrogel paste laden with the angiogenic factor VEGF (vascular endothelial growth factor) is investigated with regard to biological response in vitro and in vivo. Rat mesenchymal stromal cells are able to adhere and grow on both CPC and AlgGG strands, and differentiate toward osteoblasts. A sustained VEGF release is observed, which is able to stimulate endothelial cell proliferation as well as angiogenesis in vitro that indicates maintenance of its biological activity. After implantation into a segmental bone defect in the femur diaphysis of rats, a clear reduction of the defect size by newly formed bone tissue occurs from the distal and proximal ends of the host bone within 12 weeks. The CPC component shows excellent osteoconductivity whereas the local VEGF release from the AlgGG hydrogel gives rise to an enhanced vascularization of the defect region. This work contributes to the development of novel therapeutic concepts for improved bone regeneration which are based on 3D bioprinting.
3D extrusion‐based bioprinting is a promising method to fabricate precisely fitting implants containing biological factors for bone regeneration. Herein, hybrid scaffolds consisting of a calcium phosphate cement (CPC) and a biomaterial ink laden with a pro‐angiogenic growth factor are fabricated and investigated in vitro and in vivo. The results show biocompatibility, new bone formation along CPC, and improved vascularization of the scaffolds.</description><identifier>ISSN: 2192-2640</identifier><identifier>EISSN: 2192-2659</identifier><identifier>DOI: 10.1002/adhm.201801512</identifier><identifier>PMID: 30838778</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Alginates ; Alginic acid ; Angiogenesis ; Biocompatibility ; Biological activity ; Biomedical materials ; bone formation ; Bone growth ; Calcium ; calcium phosphate cement ; Calcium phosphates ; Cell proliferation ; Defects ; Diaphysis ; Endothelial cells ; Extrusion ; Fabrication ; Femur ; Gellan gum ; Growth factors ; Hydrogels ; Implantation ; In vivo methods and tests ; Mechanical loading ; Mesenchyme ; multichannel 3D plotting ; Osteoblasts ; Osteoconduction ; osteogenic differentiation ; Regeneration ; Regeneration (physiology) ; Scaffolds ; Stromal cells ; Surgical implants ; Three dimensional printing ; Tissue engineering ; Vascular endothelial growth factor ; Vascularization ; VEGF</subject><ispartof>Advanced healthcare materials, 2019-04, Vol.8 (7), p.e1801512-n/a</ispartof><rights>2019 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4102-9d1841d69c727b90d14c93a17b9dd8dd1564bfa96c5dd3039848163d081394b53</citedby><cites>FETCH-LOGICAL-c4102-9d1841d69c727b90d14c93a17b9dd8dd1564bfa96c5dd3039848163d081394b53</cites><orcidid>0000-0001-7704-6435</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fadhm.201801512$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fadhm.201801512$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30838778$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ahlfeld, Tilman</creatorcontrib><creatorcontrib>Schuster, Felix Paul</creatorcontrib><creatorcontrib>Förster, Yvonne</creatorcontrib><creatorcontrib>Quade, Mandy</creatorcontrib><creatorcontrib>Akkineni, Ashwini Rahul</creatorcontrib><creatorcontrib>Rentsch, Claudia</creatorcontrib><creatorcontrib>Rammelt, Stefan</creatorcontrib><creatorcontrib>Gelinsky, Michael</creatorcontrib><creatorcontrib>Lode, Anja</creatorcontrib><title>3D Plotted Biphasic Bone Scaffolds for Growth Factor Delivery: Biological Characterization In Vitro and In Vivo</title><title>Advanced healthcare materials</title><addtitle>Adv Healthc Mater</addtitle><description>Bioprinting enables the integration of biological components into scaffolds during fabrication that has the advantage of high loading efficiency and better control of release and/or spatial positioning. In this study, a biphasic scaffold fabricated by extrusion‐based 3D multichannel plotting of a calcium phosphate cement (CPC) paste and an alginate/gellan gum (AlgGG) hydrogel paste laden with the angiogenic factor VEGF (vascular endothelial growth factor) is investigated with regard to biological response in vitro and in vivo. Rat mesenchymal stromal cells are able to adhere and grow on both CPC and AlgGG strands, and differentiate toward osteoblasts. A sustained VEGF release is observed, which is able to stimulate endothelial cell proliferation as well as angiogenesis in vitro that indicates maintenance of its biological activity. After implantation into a segmental bone defect in the femur diaphysis of rats, a clear reduction of the defect size by newly formed bone tissue occurs from the distal and proximal ends of the host bone within 12 weeks. The CPC component shows excellent osteoconductivity whereas the local VEGF release from the AlgGG hydrogel gives rise to an enhanced vascularization of the defect region. This work contributes to the development of novel therapeutic concepts for improved bone regeneration which are based on 3D bioprinting.
3D extrusion‐based bioprinting is a promising method to fabricate precisely fitting implants containing biological factors for bone regeneration. Herein, hybrid scaffolds consisting of a calcium phosphate cement (CPC) and a biomaterial ink laden with a pro‐angiogenic growth factor are fabricated and investigated in vitro and in vivo. The results show biocompatibility, new bone formation along CPC, and improved vascularization of the scaffolds.</description><subject>Alginates</subject><subject>Alginic acid</subject><subject>Angiogenesis</subject><subject>Biocompatibility</subject><subject>Biological activity</subject><subject>Biomedical materials</subject><subject>bone formation</subject><subject>Bone growth</subject><subject>Calcium</subject><subject>calcium phosphate cement</subject><subject>Calcium phosphates</subject><subject>Cell proliferation</subject><subject>Defects</subject><subject>Diaphysis</subject><subject>Endothelial cells</subject><subject>Extrusion</subject><subject>Fabrication</subject><subject>Femur</subject><subject>Gellan gum</subject><subject>Growth factors</subject><subject>Hydrogels</subject><subject>Implantation</subject><subject>In vivo methods and tests</subject><subject>Mechanical loading</subject><subject>Mesenchyme</subject><subject>multichannel 3D plotting</subject><subject>Osteoblasts</subject><subject>Osteoconduction</subject><subject>osteogenic differentiation</subject><subject>Regeneration</subject><subject>Regeneration (physiology)</subject><subject>Scaffolds</subject><subject>Stromal cells</subject><subject>Surgical implants</subject><subject>Three dimensional printing</subject><subject>Tissue engineering</subject><subject>Vascular endothelial growth factor</subject><subject>Vascularization</subject><subject>VEGF</subject><issn>2192-2640</issn><issn>2192-2659</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqFkU1PIzEMhiO0CBBw5YgicdlLS5zMZJK9QcuXBAKJj2uUJpltUDopyRRUfj1BhSLtZX2xLT9-ZflF6ADIEAihx9pOZ0NKQBCogW6gHQqSDiiv5a91XZFttJ_zMynBa-ACttA2I4KJphE7KLIxvgux753Fp34-1dkbfBo7h--NbtsYbMZtTPgixbd-is-16Us3dsG_urT8U3ZiiH-90QGPpjqVsUv-Xfc-dviqw0--TxHrzq6a17iHNlsdstv_yrvo8fzsYXQ5uL69uBqdXA9MBYQOpAVRgeXSNLSZSGKhMpJpKLW1wlqoeTVpteSmtpYRJkUlgDNLBDBZTWq2i36vdOcpvixc7tXMZ-NC0J2Li6woCFGLhgpR0KN_0Oe4SF25TlFKOK05EbJQwxVlUsw5uVbNk5_ptFRA1Kcb6tMNtXajLBx-yS4mM2fX-PfvCyBXwJsPbvkfOXUyvrz5Ef8Ahy-UAg</recordid><startdate>201904</startdate><enddate>201904</enddate><creator>Ahlfeld, Tilman</creator><creator>Schuster, Felix Paul</creator><creator>Förster, Yvonne</creator><creator>Quade, Mandy</creator><creator>Akkineni, Ashwini Rahul</creator><creator>Rentsch, Claudia</creator><creator>Rammelt, Stefan</creator><creator>Gelinsky, Michael</creator><creator>Lode, Anja</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QP</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T5</scope><scope>7TA</scope><scope>7TB</scope><scope>7TM</scope><scope>7TO</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7704-6435</orcidid></search><sort><creationdate>201904</creationdate><title>3D Plotted Biphasic Bone Scaffolds for Growth Factor Delivery: Biological Characterization In Vitro and In Vivo</title><author>Ahlfeld, Tilman ; Schuster, Felix Paul ; Förster, Yvonne ; Quade, Mandy ; Akkineni, Ashwini Rahul ; Rentsch, Claudia ; Rammelt, Stefan ; Gelinsky, Michael ; Lode, Anja</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4102-9d1841d69c727b90d14c93a17b9dd8dd1564bfa96c5dd3039848163d081394b53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Alginates</topic><topic>Alginic acid</topic><topic>Angiogenesis</topic><topic>Biocompatibility</topic><topic>Biological activity</topic><topic>Biomedical materials</topic><topic>bone formation</topic><topic>Bone growth</topic><topic>Calcium</topic><topic>calcium phosphate cement</topic><topic>Calcium phosphates</topic><topic>Cell proliferation</topic><topic>Defects</topic><topic>Diaphysis</topic><topic>Endothelial cells</topic><topic>Extrusion</topic><topic>Fabrication</topic><topic>Femur</topic><topic>Gellan gum</topic><topic>Growth factors</topic><topic>Hydrogels</topic><topic>Implantation</topic><topic>In vivo methods and tests</topic><topic>Mechanical loading</topic><topic>Mesenchyme</topic><topic>multichannel 3D plotting</topic><topic>Osteoblasts</topic><topic>Osteoconduction</topic><topic>osteogenic differentiation</topic><topic>Regeneration</topic><topic>Regeneration (physiology)</topic><topic>Scaffolds</topic><topic>Stromal cells</topic><topic>Surgical implants</topic><topic>Three dimensional printing</topic><topic>Tissue engineering</topic><topic>Vascular endothelial growth factor</topic><topic>Vascularization</topic><topic>VEGF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ahlfeld, Tilman</creatorcontrib><creatorcontrib>Schuster, Felix Paul</creatorcontrib><creatorcontrib>Förster, Yvonne</creatorcontrib><creatorcontrib>Quade, Mandy</creatorcontrib><creatorcontrib>Akkineni, Ashwini Rahul</creatorcontrib><creatorcontrib>Rentsch, Claudia</creatorcontrib><creatorcontrib>Rammelt, Stefan</creatorcontrib><creatorcontrib>Gelinsky, Michael</creatorcontrib><creatorcontrib>Lode, Anja</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Calcium & Calcified Tissue 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>Immunology Abstracts</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</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>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</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>MEDLINE - Academic</collection><jtitle>Advanced healthcare materials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ahlfeld, Tilman</au><au>Schuster, Felix Paul</au><au>Förster, Yvonne</au><au>Quade, Mandy</au><au>Akkineni, Ashwini Rahul</au><au>Rentsch, Claudia</au><au>Rammelt, Stefan</au><au>Gelinsky, Michael</au><au>Lode, Anja</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>3D Plotted Biphasic Bone Scaffolds for Growth Factor Delivery: Biological Characterization In Vitro and In Vivo</atitle><jtitle>Advanced healthcare materials</jtitle><addtitle>Adv Healthc Mater</addtitle><date>2019-04</date><risdate>2019</risdate><volume>8</volume><issue>7</issue><spage>e1801512</spage><epage>n/a</epage><pages>e1801512-n/a</pages><issn>2192-2640</issn><eissn>2192-2659</eissn><abstract>Bioprinting enables the integration of biological components into scaffolds during fabrication that has the advantage of high loading efficiency and better control of release and/or spatial positioning. In this study, a biphasic scaffold fabricated by extrusion‐based 3D multichannel plotting of a calcium phosphate cement (CPC) paste and an alginate/gellan gum (AlgGG) hydrogel paste laden with the angiogenic factor VEGF (vascular endothelial growth factor) is investigated with regard to biological response in vitro and in vivo. Rat mesenchymal stromal cells are able to adhere and grow on both CPC and AlgGG strands, and differentiate toward osteoblasts. A sustained VEGF release is observed, which is able to stimulate endothelial cell proliferation as well as angiogenesis in vitro that indicates maintenance of its biological activity. After implantation into a segmental bone defect in the femur diaphysis of rats, a clear reduction of the defect size by newly formed bone tissue occurs from the distal and proximal ends of the host bone within 12 weeks. The CPC component shows excellent osteoconductivity whereas the local VEGF release from the AlgGG hydrogel gives rise to an enhanced vascularization of the defect region. This work contributes to the development of novel therapeutic concepts for improved bone regeneration which are based on 3D bioprinting.
3D extrusion‐based bioprinting is a promising method to fabricate precisely fitting implants containing biological factors for bone regeneration. Herein, hybrid scaffolds consisting of a calcium phosphate cement (CPC) and a biomaterial ink laden with a pro‐angiogenic growth factor are fabricated and investigated in vitro and in vivo. The results show biocompatibility, new bone formation along CPC, and improved vascularization of the scaffolds.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30838778</pmid><doi>10.1002/adhm.201801512</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0001-7704-6435</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2192-2640 |
| ispartof | Advanced healthcare materials, 2019-04, Vol.8 (7), p.e1801512-n/a |
| issn | 2192-2640 2192-2659 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2188587288 |
| source | Wiley Online Library Journals Frontfile Complete |
| subjects | Alginates Alginic acid Angiogenesis Biocompatibility Biological activity Biomedical materials bone formation Bone growth Calcium calcium phosphate cement Calcium phosphates Cell proliferation Defects Diaphysis Endothelial cells Extrusion Fabrication Femur Gellan gum Growth factors Hydrogels Implantation In vivo methods and tests Mechanical loading Mesenchyme multichannel 3D plotting Osteoblasts Osteoconduction osteogenic differentiation Regeneration Regeneration (physiology) Scaffolds Stromal cells Surgical implants Three dimensional printing Tissue engineering Vascular endothelial growth factor Vascularization VEGF |
| title | 3D Plotted Biphasic Bone Scaffolds for Growth Factor Delivery: Biological Characterization In Vitro and In Vivo |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-20T17%3A27%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=3D%20Plotted%20Biphasic%20Bone%20Scaffolds%20for%20Growth%20Factor%20Delivery:%20Biological%20Characterization%20In%20Vitro%20and%20In%20Vivo&rft.jtitle=Advanced%20healthcare%20materials&rft.au=Ahlfeld,%20Tilman&rft.date=2019-04&rft.volume=8&rft.issue=7&rft.spage=e1801512&rft.epage=n/a&rft.pages=e1801512-n/a&rft.issn=2192-2640&rft.eissn=2192-2659&rft_id=info:doi/10.1002/adhm.201801512&rft_dat=%3Cproquest_cross%3E2206256089%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=2206256089&rft_id=info:pmid/30838778&rfr_iscdi=true |