A decellularized flowable placental connective tissue matrix supports cellular functions of human tenocytes in vitro

Abstract Purpose Injectable connective tissue matrices (CTMs) may promote tendon healing, given their minimally invasive properties, structural and biochemical extracellular matrix components, and capacity to fill irregular spaces. The purpose of this study is to evaluate the effects of placental CT...

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Main Authors: Yong Mao, Nikita John, Nicole M. Protzman, Adam Kuehn, Desiree Long, Raja Sivalenka, Radoslaw A. Junka, Anna Gosiewska, Robert J. Hariri, Stephen A. Brigido
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Journal of Experimental Orthopaedics
Subjects:
Online Access:https://doi.org/10.1186/s40634-022-00509-4
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author Yong Mao
Nikita John
Nicole M. Protzman
Adam Kuehn
Desiree Long
Raja Sivalenka
Radoslaw A. Junka
Anna Gosiewska
Robert J. Hariri
Stephen A. Brigido
author_facet Yong Mao
Nikita John
Nicole M. Protzman
Adam Kuehn
Desiree Long
Raja Sivalenka
Radoslaw A. Junka
Anna Gosiewska
Robert J. Hariri
Stephen A. Brigido
author_sort Yong Mao
collection DOAJ
description Abstract Purpose Injectable connective tissue matrices (CTMs) may promote tendon healing, given their minimally invasive properties, structural and biochemical extracellular matrix components, and capacity to fill irregular spaces. The purpose of this study is to evaluate the effects of placental CTMs on the cellular activities of human tenocytes. Decellularization, the removal of cells, cell fragments, and DNA from CTMs, has been shown to reduce the host’s inflammatory response. Therefore, the authors hypothesize that a decellularized CTM will provide a more cell‐friendly matrix to support tenocyte functions. Methods Three human placental CTMs were selected for comparison: AmnioFill® (A‐CTM), a minimally manipulated, non‐viable cellular particulate, BioRenew™ (B‐CTM), a liquid matrix, and Interfyl® (I‐CTM), a decellularized flowable particulate. Adhesion and proliferation were evaluated using cell viability assays and tenocyte migration using a transwell migration assay. Gene expression of tenocyte markers, cytokines, growth factors, and matrix metalloprotease (MMP) in tenocytes were assessed using quantitative polymerase chain reaction. Results Although A‐CTM supported more tenocyte adhesion, I‐CTM promoted significantly more tenocyte proliferation compared with A‐CTM and B‐CTM. Unlike A‐CTM, tenocyte migration was higher in I‐CTM than the control. The presence of I‐CTM also prevented the loss of tenocyte phenotype, attenuated the expression of pro‐inflammatory cytokines, growth factors, and MMP, and promoted the expression of antifibrotic growth factor, TGFβ3. Conclusion Compared with A‐CTM and B‐CTM, I‐CTM interacted more favorably with human tenocytes in vitro. I‐CTM supported tenocyte proliferation with reduced de‐differentiation and attenuation of the inflammatory response, suggesting that I‐CTM may support tendon healing and regeneration in vivo.
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spelling doaj.art-97420117af4d4e6fb8f635d96fa9b7252024-02-07T14:50:37ZengWileyJournal of Experimental Orthopaedics2197-11532022-01-0191n/an/a10.1186/s40634-022-00509-4A decellularized flowable placental connective tissue matrix supports cellular functions of human tenocytes in vitroYong Mao0Nikita John1Nicole M. Protzman2Adam Kuehn3Desiree Long4Raja Sivalenka5Radoslaw A. Junka6Anna Gosiewska7Robert J. Hariri8Stephen A. Brigido9Laboratory for Biomaterials ResearchDepartment of Chemistry and Chemical BiologyRutgers University145 Bevier Rd.08854PiscatawayNJUSALaboratory for Biomaterials ResearchDepartment of Chemistry and Chemical BiologyRutgers University145 Bevier Rd.08854PiscatawayNJUSAHealthcare AnalyticsLLC78 Morningside Dr.18045EastonPAUSAResearch & DevelopmentDegenerative DiseasesCelularity Inc.170 Park Ave.07932Florham ParkNJUSAResearch & DevelopmentDegenerative DiseasesCelularity Inc.170 Park Ave.07932Florham ParkNJUSAResearch & DevelopmentDegenerative DiseasesCelularity Inc.170 Park Ave.07932Florham ParkNJUSAResearch & DevelopmentDegenerative DiseasesCelularity Inc.170 Park Ave.07932Florham ParkNJUSAResearch & DevelopmentDegenerative DiseasesCelularity Inc.170 Park Ave.07932Florham ParkNJUSAResearch & DevelopmentDegenerative DiseasesCelularity Inc.170 Park Ave.07932Florham ParkNJUSAResearch & DevelopmentDegenerative DiseasesCelularity Inc.170 Park Ave.07932Florham ParkNJUSAAbstract Purpose Injectable connective tissue matrices (CTMs) may promote tendon healing, given their minimally invasive properties, structural and biochemical extracellular matrix components, and capacity to fill irregular spaces. The purpose of this study is to evaluate the effects of placental CTMs on the cellular activities of human tenocytes. Decellularization, the removal of cells, cell fragments, and DNA from CTMs, has been shown to reduce the host’s inflammatory response. Therefore, the authors hypothesize that a decellularized CTM will provide a more cell‐friendly matrix to support tenocyte functions. Methods Three human placental CTMs were selected for comparison: AmnioFill® (A‐CTM), a minimally manipulated, non‐viable cellular particulate, BioRenew™ (B‐CTM), a liquid matrix, and Interfyl® (I‐CTM), a decellularized flowable particulate. Adhesion and proliferation were evaluated using cell viability assays and tenocyte migration using a transwell migration assay. Gene expression of tenocyte markers, cytokines, growth factors, and matrix metalloprotease (MMP) in tenocytes were assessed using quantitative polymerase chain reaction. Results Although A‐CTM supported more tenocyte adhesion, I‐CTM promoted significantly more tenocyte proliferation compared with A‐CTM and B‐CTM. Unlike A‐CTM, tenocyte migration was higher in I‐CTM than the control. The presence of I‐CTM also prevented the loss of tenocyte phenotype, attenuated the expression of pro‐inflammatory cytokines, growth factors, and MMP, and promoted the expression of antifibrotic growth factor, TGFβ3. Conclusion Compared with A‐CTM and B‐CTM, I‐CTM interacted more favorably with human tenocytes in vitro. I‐CTM supported tenocyte proliferation with reduced de‐differentiation and attenuation of the inflammatory response, suggesting that I‐CTM may support tendon healing and regeneration in vivo.https://doi.org/10.1186/s40634-022-00509-4BiomaterialsExtracellular matrixFlowableInflammatory responseInjectable scaffoldPlacenta
spellingShingle Yong Mao
Nikita John
Nicole M. Protzman
Adam Kuehn
Desiree Long
Raja Sivalenka
Radoslaw A. Junka
Anna Gosiewska
Robert J. Hariri
Stephen A. Brigido
A decellularized flowable placental connective tissue matrix supports cellular functions of human tenocytes in vitro
Journal of Experimental Orthopaedics
Biomaterials
Extracellular matrix
Flowable
Inflammatory response
Injectable scaffold
Placenta
title A decellularized flowable placental connective tissue matrix supports cellular functions of human tenocytes in vitro
title_full A decellularized flowable placental connective tissue matrix supports cellular functions of human tenocytes in vitro
title_fullStr A decellularized flowable placental connective tissue matrix supports cellular functions of human tenocytes in vitro
title_full_unstemmed A decellularized flowable placental connective tissue matrix supports cellular functions of human tenocytes in vitro
title_short A decellularized flowable placental connective tissue matrix supports cellular functions of human tenocytes in vitro
title_sort decellularized flowable placental connective tissue matrix supports cellular functions of human tenocytes in vitro
topic Biomaterials
Extracellular matrix
Flowable
Inflammatory response
Injectable scaffold
Placenta
url https://doi.org/10.1186/s40634-022-00509-4
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