Acute Elution of TGFβ2 Affects the Smooth Muscle Cells in a Compliance-Matched Vascular Graft
Transforming growth factor beta 2 (TGFβ2) is a pleiotropic growth factor that plays a vital role in smooth muscle cell (SMC) function. Our prior in vitro work has shown that SMC response can be modulated with TGFβ2 stimulation in a dose dependent manner. In particular, we have shown that increasing...
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| Veröffentlicht in: | Tissue engineering. Part A 2022-07, Vol.28 (13-14), p.64-650 |
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| creator | Furdella, Kenneth J Higuchi, Shinichi Kim, Kang Doetschman, Tom Wagner, William R Vande Geest, Jonathan P |
| description | Transforming growth factor beta 2 (TGFβ2) is a pleiotropic growth factor that plays a vital role in smooth muscle cell (SMC) function. Our prior
in vitro
work has shown that SMC response can be modulated with TGFβ2 stimulation in a dose dependent manner. In particular, we have shown that increasing concentrations of TGFβ2 shift SMCs from a migratory to a synthetic behavior. In this work, electrospun compliance-matched and hypocompliant TGFβ2-eluting tissue engineered vascular grafts (TEVGs) were implanted into Sprague Dawley rats for 5 days to observe SMC population and collagen production. TEVGs were fabricated using a combined computational and experimental approach that varied the ratio of gelatin:polycaprolactone to be either compliance matched or twice as stiff as rat aorta (hypocompliant). TGFβ2 concentrations of 0, 10, 100 ng/mg were added to both graft types (
n
= 3 in each group) and imaged
in vivo
using ultrasound. Histological markers (SMC, macrophage, collagen, and elastin) were evaluated following explanation at 5 days.
In vivo
ultrasound showed that compliance-matched TEVGs became stiffer as TGFβ2 increased (100 ng/mg TEVGs compared to rat aorta,
p
|
| doi_str_mv | 10.1089/ten.tea.2021.0161 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9354035</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2689212913</sourcerecordid><originalsourceid>FETCH-LOGICAL-c347t-ca0ee8251500231e77cb046e76f9f20483745d33093bea62858cb8ad3cafb86f3</originalsourceid><addsrcrecordid>eNqNkc1uEzEUhS0EoqXwAGyQJTbdTPDP2J7ZIEVRGyq1YkFBrLA8zjWZymMH24PEa_EgPBOO0kbAioV1Ld_vHt3jg9BLShaUdP2bAmFRwCwYYXRBqKSP0CntuWo4F58fH-8tPUHPcr4jRBKp1FN0woVgVLb9KfqytHMBfOHnMsaAo8O368tfPxleOge2ZFy2gD9MMZYtvpmz9YBX4H3GY8AGr-K086MJFpobU-wWNviTyXb2JuF1Mq48R0-c8Rle3Ncz9PHy4nb1rrl-v75aLa8by1tVGmsIQMcEFYQwTkEpO5BWgpKud4y0HVet2HBOej6AkawTnR06s-HWuKGTjp-htwfd3TxMsLEQSjJe79I4mfRDRzPqvzth3Oqv8bvuuWgJF1Xg_F4gxW8z5KKnMdvq1ASIc9ZMyvrlXDBW0df_oHdxTqHaq1TXM8p6yitFD5RNMecE7rgMJXqfnq7p1WP0Pj29T6_OvPrTxXHiIa4KqAOwfzYh-BEGSOU_pH8DPxaqEw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2689212913</pqid></control><display><type>article</type><title>Acute Elution of TGFβ2 Affects the Smooth Muscle Cells in a Compliance-Matched Vascular Graft</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Furdella, Kenneth J ; Higuchi, Shinichi ; Kim, Kang ; Doetschman, Tom ; Wagner, William R ; Vande Geest, Jonathan P</creator><creatorcontrib>Furdella, Kenneth J ; Higuchi, Shinichi ; Kim, Kang ; Doetschman, Tom ; Wagner, William R ; Vande Geest, Jonathan P</creatorcontrib><description>Transforming growth factor beta 2 (TGFβ2) is a pleiotropic growth factor that plays a vital role in smooth muscle cell (SMC) function. Our prior
in vitro
work has shown that SMC response can be modulated with TGFβ2 stimulation in a dose dependent manner. In particular, we have shown that increasing concentrations of TGFβ2 shift SMCs from a migratory to a synthetic behavior. In this work, electrospun compliance-matched and hypocompliant TGFβ2-eluting tissue engineered vascular grafts (TEVGs) were implanted into Sprague Dawley rats for 5 days to observe SMC population and collagen production. TEVGs were fabricated using a combined computational and experimental approach that varied the ratio of gelatin:polycaprolactone to be either compliance matched or twice as stiff as rat aorta (hypocompliant). TGFβ2 concentrations of 0, 10, 100 ng/mg were added to both graft types (
n
= 3 in each group) and imaged
in vivo
using ultrasound. Histological markers (SMC, macrophage, collagen, and elastin) were evaluated following explanation at 5 days.
In vivo
ultrasound showed that compliance-matched TEVGs became stiffer as TGFβ2 increased (100 ng/mg TEVGs compared to rat aorta,
p
< 0.01), while all hypocompliant grafts remained stiffer than control rat aorta.
In vivo
velocity and diameter were also not significantly different than control vessels. The compliance-matched 10 ng/mg group had an elevated SMC signal (myosin heavy chain) compared to the 0 and 100 ng/mg grafts (
p
= 0.0009 and 0.0006). Compliance-matched TEVGs containing 100 ng/mg TGFβ2 had an increase in collagen production (
p
< 0.01), general immune response (
p
< 0.05), and a decrease in SMC population to the 0 and 10 ng/mg groups. All hypocompliant groups were found to be similar, suggesting a lower rate of TGFβ2 release in these TEVGs. Our results suggest that TGFβ2 can modulate
in vivo
SMC phenotype over an acute implantation period, which is consistent with our prior
in vitro
work. To the author's knowledge, this is the first
in vivo
rat study that evaluates a TGFβ2-eluting TEVG.</description><identifier>ISSN: 1937-3341</identifier><identifier>EISSN: 1937-335X</identifier><identifier>DOI: 10.1089/ten.tea.2021.0161</identifier><identifier>PMID: 35521649</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc., publishers</publisher><subject>Animals ; Aorta ; Blood Vessel Prosthesis ; Collagen ; Collagen - metabolism ; Compliance ; Computer applications ; Coronary vessels ; Elastin ; Gelatin ; Growth factors ; Immune response ; Macrophages ; Myocytes, Smooth Muscle - drug effects ; Myocytes, Smooth Muscle - metabolism ; Myosin ; Original ; Original Articles ; Phenotypes ; Polycaprolactone ; Rats ; Rats, Sprague-Dawley ; Smooth muscle ; Tissue engineering ; Transforming Growth Factor beta2 - administration & dosage ; Transforming Growth Factor beta2 - pharmacology ; Transforming growth factor-b1 ; Ultrasonic imaging ; Ultrasound</subject><ispartof>Tissue engineering. Part A, 2022-07, Vol.28 (13-14), p.64-650</ispartof><rights>2022, Mary Ann Liebert, Inc., publishers</rights><rights>Copyright Mary Ann Liebert, Inc. Jul 2022</rights><rights>Copyright 2022, Mary Ann Liebert, Inc., publishers 2022 Mary Ann Liebert, Inc., publishers</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c347t-ca0ee8251500231e77cb046e76f9f20483745d33093bea62858cb8ad3cafb86f3</citedby><cites>FETCH-LOGICAL-c347t-ca0ee8251500231e77cb046e76f9f20483745d33093bea62858cb8ad3cafb86f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35521649$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Furdella, Kenneth J</creatorcontrib><creatorcontrib>Higuchi, Shinichi</creatorcontrib><creatorcontrib>Kim, Kang</creatorcontrib><creatorcontrib>Doetschman, Tom</creatorcontrib><creatorcontrib>Wagner, William R</creatorcontrib><creatorcontrib>Vande Geest, Jonathan P</creatorcontrib><title>Acute Elution of TGFβ2 Affects the Smooth Muscle Cells in a Compliance-Matched Vascular Graft</title><title>Tissue engineering. Part A</title><addtitle>Tissue Eng Part A</addtitle><description>Transforming growth factor beta 2 (TGFβ2) is a pleiotropic growth factor that plays a vital role in smooth muscle cell (SMC) function. Our prior
in vitro
work has shown that SMC response can be modulated with TGFβ2 stimulation in a dose dependent manner. In particular, we have shown that increasing concentrations of TGFβ2 shift SMCs from a migratory to a synthetic behavior. In this work, electrospun compliance-matched and hypocompliant TGFβ2-eluting tissue engineered vascular grafts (TEVGs) were implanted into Sprague Dawley rats for 5 days to observe SMC population and collagen production. TEVGs were fabricated using a combined computational and experimental approach that varied the ratio of gelatin:polycaprolactone to be either compliance matched or twice as stiff as rat aorta (hypocompliant). TGFβ2 concentrations of 0, 10, 100 ng/mg were added to both graft types (
n
= 3 in each group) and imaged
in vivo
using ultrasound. Histological markers (SMC, macrophage, collagen, and elastin) were evaluated following explanation at 5 days.
In vivo
ultrasound showed that compliance-matched TEVGs became stiffer as TGFβ2 increased (100 ng/mg TEVGs compared to rat aorta,
p
< 0.01), while all hypocompliant grafts remained stiffer than control rat aorta.
In vivo
velocity and diameter were also not significantly different than control vessels. The compliance-matched 10 ng/mg group had an elevated SMC signal (myosin heavy chain) compared to the 0 and 100 ng/mg grafts (
p
= 0.0009 and 0.0006). Compliance-matched TEVGs containing 100 ng/mg TGFβ2 had an increase in collagen production (
p
< 0.01), general immune response (
p
< 0.05), and a decrease in SMC population to the 0 and 10 ng/mg groups. All hypocompliant groups were found to be similar, suggesting a lower rate of TGFβ2 release in these TEVGs. Our results suggest that TGFβ2 can modulate
in vivo
SMC phenotype over an acute implantation period, which is consistent with our prior
in vitro
work. To the author's knowledge, this is the first
in vivo
rat study that evaluates a TGFβ2-eluting TEVG.</description><subject>Animals</subject><subject>Aorta</subject><subject>Blood Vessel Prosthesis</subject><subject>Collagen</subject><subject>Collagen - metabolism</subject><subject>Compliance</subject><subject>Computer applications</subject><subject>Coronary vessels</subject><subject>Elastin</subject><subject>Gelatin</subject><subject>Growth factors</subject><subject>Immune response</subject><subject>Macrophages</subject><subject>Myocytes, Smooth Muscle - drug effects</subject><subject>Myocytes, Smooth Muscle - metabolism</subject><subject>Myosin</subject><subject>Original</subject><subject>Original Articles</subject><subject>Phenotypes</subject><subject>Polycaprolactone</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Smooth muscle</subject><subject>Tissue engineering</subject><subject>Transforming Growth Factor beta2 - administration & dosage</subject><subject>Transforming Growth Factor beta2 - pharmacology</subject><subject>Transforming growth factor-b1</subject><subject>Ultrasonic imaging</subject><subject>Ultrasound</subject><issn>1937-3341</issn><issn>1937-335X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1uEzEUhS0EoqXwAGyQJTbdTPDP2J7ZIEVRGyq1YkFBrLA8zjWZymMH24PEa_EgPBOO0kbAioV1Ld_vHt3jg9BLShaUdP2bAmFRwCwYYXRBqKSP0CntuWo4F58fH-8tPUHPcr4jRBKp1FN0woVgVLb9KfqytHMBfOHnMsaAo8O368tfPxleOge2ZFy2gD9MMZYtvpmz9YBX4H3GY8AGr-K086MJFpobU-wWNviTyXb2JuF1Mq48R0-c8Rle3Ncz9PHy4nb1rrl-v75aLa8by1tVGmsIQMcEFYQwTkEpO5BWgpKud4y0HVet2HBOej6AkawTnR06s-HWuKGTjp-htwfd3TxMsLEQSjJe79I4mfRDRzPqvzth3Oqv8bvuuWgJF1Xg_F4gxW8z5KKnMdvq1ASIc9ZMyvrlXDBW0df_oHdxTqHaq1TXM8p6yitFD5RNMecE7rgMJXqfnq7p1WP0Pj29T6_OvPrTxXHiIa4KqAOwfzYh-BEGSOU_pH8DPxaqEw</recordid><startdate>20220701</startdate><enddate>20220701</enddate><creator>Furdella, Kenneth J</creator><creator>Higuchi, Shinichi</creator><creator>Kim, Kang</creator><creator>Doetschman, Tom</creator><creator>Wagner, William R</creator><creator>Vande Geest, Jonathan P</creator><general>Mary Ann Liebert, Inc., publishers</general><general>Mary Ann Liebert, Inc</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>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20220701</creationdate><title>Acute Elution of TGFβ2 Affects the Smooth Muscle Cells in a Compliance-Matched Vascular Graft</title><author>Furdella, Kenneth J ; Higuchi, Shinichi ; Kim, Kang ; Doetschman, Tom ; Wagner, William R ; Vande Geest, Jonathan P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c347t-ca0ee8251500231e77cb046e76f9f20483745d33093bea62858cb8ad3cafb86f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Aorta</topic><topic>Blood Vessel Prosthesis</topic><topic>Collagen</topic><topic>Collagen - metabolism</topic><topic>Compliance</topic><topic>Computer applications</topic><topic>Coronary vessels</topic><topic>Elastin</topic><topic>Gelatin</topic><topic>Growth factors</topic><topic>Immune response</topic><topic>Macrophages</topic><topic>Myocytes, Smooth Muscle - drug effects</topic><topic>Myocytes, Smooth Muscle - metabolism</topic><topic>Myosin</topic><topic>Original</topic><topic>Original Articles</topic><topic>Phenotypes</topic><topic>Polycaprolactone</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Smooth muscle</topic><topic>Tissue engineering</topic><topic>Transforming Growth Factor beta2 - administration & dosage</topic><topic>Transforming Growth Factor beta2 - pharmacology</topic><topic>Transforming growth factor-b1</topic><topic>Ultrasonic imaging</topic><topic>Ultrasound</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Furdella, Kenneth J</creatorcontrib><creatorcontrib>Higuchi, Shinichi</creatorcontrib><creatorcontrib>Kim, Kang</creatorcontrib><creatorcontrib>Doetschman, Tom</creatorcontrib><creatorcontrib>Wagner, William R</creatorcontrib><creatorcontrib>Vande Geest, Jonathan P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Tissue engineering. Part A</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Furdella, Kenneth J</au><au>Higuchi, Shinichi</au><au>Kim, Kang</au><au>Doetschman, Tom</au><au>Wagner, William R</au><au>Vande Geest, Jonathan P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acute Elution of TGFβ2 Affects the Smooth Muscle Cells in a Compliance-Matched Vascular Graft</atitle><jtitle>Tissue engineering. Part A</jtitle><addtitle>Tissue Eng Part A</addtitle><date>2022-07-01</date><risdate>2022</risdate><volume>28</volume><issue>13-14</issue><spage>64</spage><epage>650</epage><pages>64-650</pages><issn>1937-3341</issn><eissn>1937-335X</eissn><abstract>Transforming growth factor beta 2 (TGFβ2) is a pleiotropic growth factor that plays a vital role in smooth muscle cell (SMC) function. Our prior
in vitro
work has shown that SMC response can be modulated with TGFβ2 stimulation in a dose dependent manner. In particular, we have shown that increasing concentrations of TGFβ2 shift SMCs from a migratory to a synthetic behavior. In this work, electrospun compliance-matched and hypocompliant TGFβ2-eluting tissue engineered vascular grafts (TEVGs) were implanted into Sprague Dawley rats for 5 days to observe SMC population and collagen production. TEVGs were fabricated using a combined computational and experimental approach that varied the ratio of gelatin:polycaprolactone to be either compliance matched or twice as stiff as rat aorta (hypocompliant). TGFβ2 concentrations of 0, 10, 100 ng/mg were added to both graft types (
n
= 3 in each group) and imaged
in vivo
using ultrasound. Histological markers (SMC, macrophage, collagen, and elastin) were evaluated following explanation at 5 days.
In vivo
ultrasound showed that compliance-matched TEVGs became stiffer as TGFβ2 increased (100 ng/mg TEVGs compared to rat aorta,
p
< 0.01), while all hypocompliant grafts remained stiffer than control rat aorta.
In vivo
velocity and diameter were also not significantly different than control vessels. The compliance-matched 10 ng/mg group had an elevated SMC signal (myosin heavy chain) compared to the 0 and 100 ng/mg grafts (
p
= 0.0009 and 0.0006). Compliance-matched TEVGs containing 100 ng/mg TGFβ2 had an increase in collagen production (
p
< 0.01), general immune response (
p
< 0.05), and a decrease in SMC population to the 0 and 10 ng/mg groups. All hypocompliant groups were found to be similar, suggesting a lower rate of TGFβ2 release in these TEVGs. Our results suggest that TGFβ2 can modulate
in vivo
SMC phenotype over an acute implantation period, which is consistent with our prior
in vitro
work. To the author's knowledge, this is the first
in vivo
rat study that evaluates a TGFβ2-eluting TEVG.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc., publishers</pub><pmid>35521649</pmid><doi>10.1089/ten.tea.2021.0161</doi><tpages>587</tpages></addata></record> |
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| ispartof | Tissue engineering. Part A, 2022-07, Vol.28 (13-14), p.64-650 |
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| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9354035 |
| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Animals Aorta Blood Vessel Prosthesis Collagen Collagen - metabolism Compliance Computer applications Coronary vessels Elastin Gelatin Growth factors Immune response Macrophages Myocytes, Smooth Muscle - drug effects Myocytes, Smooth Muscle - metabolism Myosin Original Original Articles Phenotypes Polycaprolactone Rats Rats, Sprague-Dawley Smooth muscle Tissue engineering Transforming Growth Factor beta2 - administration & dosage Transforming Growth Factor beta2 - pharmacology Transforming growth factor-b1 Ultrasonic imaging Ultrasound |
| title | Acute Elution of TGFβ2 Affects the Smooth Muscle Cells in a Compliance-Matched Vascular Graft |
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