Monitoring Bone Tissue Engineered (BTE) Constructs Based on the Shifting Metabolism of Differentiating Stem Cells

Ever-increasing demand for bone grafts necessitates the realization of clinical implementation of bone tissue engineered constructs. The predominant hurdle to implementation remains to be securing FDA approval, based on the lack of viable methods for the rigorous monitoring of said constructs. The s...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Annals of biomedical engineering 2018, Vol.46 (1), p.37-47
Hauptverfasser: Simmons, Aaron D., Sikavitsas, Vassilios I.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 47
container_issue 1
container_start_page 37
container_title Annals of biomedical engineering
container_volume 46
creator Simmons, Aaron D.
Sikavitsas, Vassilios I.
description Ever-increasing demand for bone grafts necessitates the realization of clinical implementation of bone tissue engineered constructs. The predominant hurdle to implementation remains to be securing FDA approval, based on the lack of viable methods for the rigorous monitoring of said constructs. The study presented herein details a method for such monitoring based on the shifting metabolism of mesenchymal stem cells (MSCs) as they differentiate into osteoblasts. To that end, rat MSCs seeded on 85% porous spunbonded poly(L-lactic acid) scaffolds were cultured in flow perfusion bioreactors with baseline or osteoinductive media, and levels of key physio-metabolic markers (oxygen, glucose, osteoprotegerin, and osteocalcin) were monitored throughout culture. Comparison of these non-destructively obtained values and current standard destructive analyses demonstrated key trends useful for the concurrent real-time monitoring of construct cellularity and maturation. Principle among these is the elucidation of the ratio of the rates of oxygen uptake to glucose consumption as a powerful quality marker. This ratio, supported on a physiological basis, has been shown herein to be reliable in the determination of both construct maturation (defined as osteoblastic differentiation and accompanying mineralization) and construct cellularity. Supplementary monitoring of OPG and OCN are shown to provide further validation of such metrics.
doi_str_mv 10.1007/s10439-017-1937-y
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1950418119</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1984680324</sourcerecordid><originalsourceid>FETCH-LOGICAL-c372t-1120670b02e9576cbfbcab44a6765273098bb4811970bc35871ee24b67d40cb63</originalsourceid><addsrcrecordid>eNp1kcFu1DAQhi0EokvLA3BBlriUQ8qM49jxkV2WUqlVD13OVpx1Wlcbe2s7h337OmxBCImTpfH3_zPSR8gHhAsEkF8SAq9VBSgrVLWsDq_IAhtZV0q04jVZACiohBL8hLxL6REAsa2bt-SEKWAMERbk6SZ4l0N0_p4ug7d041KaLF37e-etjXZLz5eb9We6Cj7lOPU50WWXyjh4mh8svXtwQ57TNzZ3JuxcGmkY6Dc3DCXts-t-_d5lO9KV3e3SGXkzdLtk37-8p-Tn9_Vm9aO6vr28Wn29rvpaslwhMhASDDCrGil6M5i-M5x3QoqGyRpUawxvEVWB-rppJVrLuBFyy6E3oj4l58fefQxPk01Zjy715YLO2zAljaoBjnNBQT_9gz6GKfpyXaFaLlqoGS8UHqk-hpSiHfQ-urGLB42gZx_66EMXH3r2oQ8l8_GleTKj3f5J_BZQAHYE0n52YONfq__b-gybT5Sy</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1984680324</pqid></control><display><type>article</type><title>Monitoring Bone Tissue Engineered (BTE) Constructs Based on the Shifting Metabolism of Differentiating Stem Cells</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Simmons, Aaron D. ; Sikavitsas, Vassilios I.</creator><creatorcontrib>Simmons, Aaron D. ; Sikavitsas, Vassilios I.</creatorcontrib><description>Ever-increasing demand for bone grafts necessitates the realization of clinical implementation of bone tissue engineered constructs. The predominant hurdle to implementation remains to be securing FDA approval, based on the lack of viable methods for the rigorous monitoring of said constructs. The study presented herein details a method for such monitoring based on the shifting metabolism of mesenchymal stem cells (MSCs) as they differentiate into osteoblasts. To that end, rat MSCs seeded on 85% porous spunbonded poly(L-lactic acid) scaffolds were cultured in flow perfusion bioreactors with baseline or osteoinductive media, and levels of key physio-metabolic markers (oxygen, glucose, osteoprotegerin, and osteocalcin) were monitored throughout culture. Comparison of these non-destructively obtained values and current standard destructive analyses demonstrated key trends useful for the concurrent real-time monitoring of construct cellularity and maturation. Principle among these is the elucidation of the ratio of the rates of oxygen uptake to glucose consumption as a powerful quality marker. This ratio, supported on a physiological basis, has been shown herein to be reliable in the determination of both construct maturation (defined as osteoblastic differentiation and accompanying mineralization) and construct cellularity. Supplementary monitoring of OPG and OCN are shown to provide further validation of such metrics.</description><identifier>ISSN: 0090-6964</identifier><identifier>EISSN: 1573-9686</identifier><identifier>DOI: 10.1007/s10439-017-1937-y</identifier><identifier>PMID: 29022110</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Animals ; Biochemistry ; Biocompatibility ; Biological and Medical Physics ; Biomedical and Life Sciences ; Biomedical Engineering and Bioengineering ; Biomedical materials ; Biomedicine ; Biophysics ; Bioreactors ; Bone and Bones - metabolism ; Bone grafts ; Bones ; Cell culture ; Cells, Cultured ; Classical Mechanics ; Construction engineering ; Culture Media - analysis ; FDA approval ; Glucose ; Glucose - metabolism ; Grafts ; Male ; Maturation ; Mesenchymal Stem Cells - metabolism ; Mesenchyme ; Metabolism ; Mineralization ; Monitoring ; Osteoblastogenesis ; Osteoblasts ; Osteocalcin ; Osteocalcin - metabolism ; Osteogenesis ; Osteoprotegerin ; Osteoprotegerin - metabolism ; Oxygen Consumption ; Oxygen uptake ; Perfusion ; Polylactic acid ; Rats, Wistar ; Regulatory agencies ; Scaffolds ; Stem cell transplantation ; Stem cells ; Tissue Engineering ; Tissue Scaffolds</subject><ispartof>Annals of biomedical engineering, 2018, Vol.46 (1), p.37-47</ispartof><rights>Biomedical Engineering Society 2017</rights><rights>Annals of Biomedical Engineering is a copyright of Springer, (2017). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-1120670b02e9576cbfbcab44a6765273098bb4811970bc35871ee24b67d40cb63</citedby><cites>FETCH-LOGICAL-c372t-1120670b02e9576cbfbcab44a6765273098bb4811970bc35871ee24b67d40cb63</cites><orcidid>0000-0002-6744-2036</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10439-017-1937-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10439-017-1937-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29022110$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Simmons, Aaron D.</creatorcontrib><creatorcontrib>Sikavitsas, Vassilios I.</creatorcontrib><title>Monitoring Bone Tissue Engineered (BTE) Constructs Based on the Shifting Metabolism of Differentiating Stem Cells</title><title>Annals of biomedical engineering</title><addtitle>Ann Biomed Eng</addtitle><addtitle>Ann Biomed Eng</addtitle><description>Ever-increasing demand for bone grafts necessitates the realization of clinical implementation of bone tissue engineered constructs. The predominant hurdle to implementation remains to be securing FDA approval, based on the lack of viable methods for the rigorous monitoring of said constructs. The study presented herein details a method for such monitoring based on the shifting metabolism of mesenchymal stem cells (MSCs) as they differentiate into osteoblasts. To that end, rat MSCs seeded on 85% porous spunbonded poly(L-lactic acid) scaffolds were cultured in flow perfusion bioreactors with baseline or osteoinductive media, and levels of key physio-metabolic markers (oxygen, glucose, osteoprotegerin, and osteocalcin) were monitored throughout culture. Comparison of these non-destructively obtained values and current standard destructive analyses demonstrated key trends useful for the concurrent real-time monitoring of construct cellularity and maturation. Principle among these is the elucidation of the ratio of the rates of oxygen uptake to glucose consumption as a powerful quality marker. This ratio, supported on a physiological basis, has been shown herein to be reliable in the determination of both construct maturation (defined as osteoblastic differentiation and accompanying mineralization) and construct cellularity. Supplementary monitoring of OPG and OCN are shown to provide further validation of such metrics.</description><subject>Animals</subject><subject>Biochemistry</subject><subject>Biocompatibility</subject><subject>Biological and Medical Physics</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Biomedical materials</subject><subject>Biomedicine</subject><subject>Biophysics</subject><subject>Bioreactors</subject><subject>Bone and Bones - metabolism</subject><subject>Bone grafts</subject><subject>Bones</subject><subject>Cell culture</subject><subject>Cells, Cultured</subject><subject>Classical Mechanics</subject><subject>Construction engineering</subject><subject>Culture Media - analysis</subject><subject>FDA approval</subject><subject>Glucose</subject><subject>Glucose - metabolism</subject><subject>Grafts</subject><subject>Male</subject><subject>Maturation</subject><subject>Mesenchymal Stem Cells - metabolism</subject><subject>Mesenchyme</subject><subject>Metabolism</subject><subject>Mineralization</subject><subject>Monitoring</subject><subject>Osteoblastogenesis</subject><subject>Osteoblasts</subject><subject>Osteocalcin</subject><subject>Osteocalcin - metabolism</subject><subject>Osteogenesis</subject><subject>Osteoprotegerin</subject><subject>Osteoprotegerin - metabolism</subject><subject>Oxygen Consumption</subject><subject>Oxygen uptake</subject><subject>Perfusion</subject><subject>Polylactic acid</subject><subject>Rats, Wistar</subject><subject>Regulatory agencies</subject><subject>Scaffolds</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Tissue Engineering</subject><subject>Tissue Scaffolds</subject><issn>0090-6964</issn><issn>1573-9686</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kcFu1DAQhi0EokvLA3BBlriUQ8qM49jxkV2WUqlVD13OVpx1Wlcbe2s7h337OmxBCImTpfH3_zPSR8gHhAsEkF8SAq9VBSgrVLWsDq_IAhtZV0q04jVZACiohBL8hLxL6REAsa2bt-SEKWAMERbk6SZ4l0N0_p4ug7d041KaLF37e-etjXZLz5eb9We6Cj7lOPU50WWXyjh4mh8svXtwQ57TNzZ3JuxcGmkY6Dc3DCXts-t-_d5lO9KV3e3SGXkzdLtk37-8p-Tn9_Vm9aO6vr28Wn29rvpaslwhMhASDDCrGil6M5i-M5x3QoqGyRpUawxvEVWB-rppJVrLuBFyy6E3oj4l58fefQxPk01Zjy715YLO2zAljaoBjnNBQT_9gz6GKfpyXaFaLlqoGS8UHqk-hpSiHfQ-urGLB42gZx_66EMXH3r2oQ8l8_GleTKj3f5J_BZQAHYE0n52YONfq__b-gybT5Sy</recordid><startdate>2018</startdate><enddate>2018</enddate><creator>Simmons, Aaron D.</creator><creator>Sikavitsas, Vassilios I.</creator><general>Springer US</general><general>Springer Nature B.V</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>3V.</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8BQ</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F28</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H8D</scope><scope>H8G</scope><scope>HCIFZ</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L6V</scope><scope>L7M</scope><scope>LK8</scope><scope>L~C</scope><scope>L~D</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>M7S</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6744-2036</orcidid></search><sort><creationdate>2018</creationdate><title>Monitoring Bone Tissue Engineered (BTE) Constructs Based on the Shifting Metabolism of Differentiating Stem Cells</title><author>Simmons, Aaron D. ; Sikavitsas, Vassilios I.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-1120670b02e9576cbfbcab44a6765273098bb4811970bc35871ee24b67d40cb63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Biochemistry</topic><topic>Biocompatibility</topic><topic>Biological and Medical Physics</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering and Bioengineering</topic><topic>Biomedical materials</topic><topic>Biomedicine</topic><topic>Biophysics</topic><topic>Bioreactors</topic><topic>Bone and Bones - metabolism</topic><topic>Bone grafts</topic><topic>Bones</topic><topic>Cell culture</topic><topic>Cells, Cultured</topic><topic>Classical Mechanics</topic><topic>Construction engineering</topic><topic>Culture Media - analysis</topic><topic>FDA approval</topic><topic>Glucose</topic><topic>Glucose - metabolism</topic><topic>Grafts</topic><topic>Male</topic><topic>Maturation</topic><topic>Mesenchymal Stem Cells - metabolism</topic><topic>Mesenchyme</topic><topic>Metabolism</topic><topic>Mineralization</topic><topic>Monitoring</topic><topic>Osteoblastogenesis</topic><topic>Osteoblasts</topic><topic>Osteocalcin</topic><topic>Osteocalcin - metabolism</topic><topic>Osteogenesis</topic><topic>Osteoprotegerin</topic><topic>Osteoprotegerin - metabolism</topic><topic>Oxygen Consumption</topic><topic>Oxygen uptake</topic><topic>Perfusion</topic><topic>Polylactic acid</topic><topic>Rats, Wistar</topic><topic>Regulatory agencies</topic><topic>Scaffolds</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Tissue Engineering</topic><topic>Tissue Scaffolds</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Simmons, Aaron D.</creatorcontrib><creatorcontrib>Sikavitsas, Vassilios I.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</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 &amp; Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Materials Business File</collection><collection>Mechanical &amp; Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ANTE: Abstracts in New Technology &amp; Engineering</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>SciTech Premium Collection</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Civil Engineering Abstracts</collection><collection>ProQuest Engineering Collection</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>ProQuest Biological Science Collection</collection><collection>Computer and Information Systems Abstracts – Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of biomedical engineering</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Simmons, Aaron D.</au><au>Sikavitsas, Vassilios I.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Monitoring Bone Tissue Engineered (BTE) Constructs Based on the Shifting Metabolism of Differentiating Stem Cells</atitle><jtitle>Annals of biomedical engineering</jtitle><stitle>Ann Biomed Eng</stitle><addtitle>Ann Biomed Eng</addtitle><date>2018</date><risdate>2018</risdate><volume>46</volume><issue>1</issue><spage>37</spage><epage>47</epage><pages>37-47</pages><issn>0090-6964</issn><eissn>1573-9686</eissn><abstract>Ever-increasing demand for bone grafts necessitates the realization of clinical implementation of bone tissue engineered constructs. The predominant hurdle to implementation remains to be securing FDA approval, based on the lack of viable methods for the rigorous monitoring of said constructs. The study presented herein details a method for such monitoring based on the shifting metabolism of mesenchymal stem cells (MSCs) as they differentiate into osteoblasts. To that end, rat MSCs seeded on 85% porous spunbonded poly(L-lactic acid) scaffolds were cultured in flow perfusion bioreactors with baseline or osteoinductive media, and levels of key physio-metabolic markers (oxygen, glucose, osteoprotegerin, and osteocalcin) were monitored throughout culture. Comparison of these non-destructively obtained values and current standard destructive analyses demonstrated key trends useful for the concurrent real-time monitoring of construct cellularity and maturation. Principle among these is the elucidation of the ratio of the rates of oxygen uptake to glucose consumption as a powerful quality marker. This ratio, supported on a physiological basis, has been shown herein to be reliable in the determination of both construct maturation (defined as osteoblastic differentiation and accompanying mineralization) and construct cellularity. Supplementary monitoring of OPG and OCN are shown to provide further validation of such metrics.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>29022110</pmid><doi>10.1007/s10439-017-1937-y</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-6744-2036</orcidid></addata></record>
fulltext fulltext
identifier ISSN: 0090-6964
ispartof Annals of biomedical engineering, 2018, Vol.46 (1), p.37-47
issn 0090-6964
1573-9686
language eng
recordid cdi_proquest_miscellaneous_1950418119
source MEDLINE; SpringerLink Journals
subjects Animals
Biochemistry
Biocompatibility
Biological and Medical Physics
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedical materials
Biomedicine
Biophysics
Bioreactors
Bone and Bones - metabolism
Bone grafts
Bones
Cell culture
Cells, Cultured
Classical Mechanics
Construction engineering
Culture Media - analysis
FDA approval
Glucose
Glucose - metabolism
Grafts
Male
Maturation
Mesenchymal Stem Cells - metabolism
Mesenchyme
Metabolism
Mineralization
Monitoring
Osteoblastogenesis
Osteoblasts
Osteocalcin
Osteocalcin - metabolism
Osteogenesis
Osteoprotegerin
Osteoprotegerin - metabolism
Oxygen Consumption
Oxygen uptake
Perfusion
Polylactic acid
Rats, Wistar
Regulatory agencies
Scaffolds
Stem cell transplantation
Stem cells
Tissue Engineering
Tissue Scaffolds
title Monitoring Bone Tissue Engineered (BTE) Constructs Based on the Shifting Metabolism of Differentiating Stem Cells
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-16T14%3A17%3A41IST&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=Monitoring%20Bone%20Tissue%20Engineered%20(BTE)%20Constructs%20Based%20on%20the%20Shifting%20Metabolism%20of%20Differentiating%20Stem%20Cells&rft.jtitle=Annals%20of%20biomedical%20engineering&rft.au=Simmons,%20Aaron%20D.&rft.date=2018&rft.volume=46&rft.issue=1&rft.spage=37&rft.epage=47&rft.pages=37-47&rft.issn=0090-6964&rft.eissn=1573-9686&rft_id=info:doi/10.1007/s10439-017-1937-y&rft_dat=%3Cproquest_cross%3E1984680324%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=1984680324&rft_id=info:pmid/29022110&rfr_iscdi=true