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...
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Veröffentlicht in: | Annals of biomedical engineering 2018, Vol.46 (1), p.37-47 |
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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. |
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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 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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 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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> |
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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 |
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