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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Format: | Article |
Language: | English |
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Wiley
2022-01-01
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Series: | Journal of Experimental Orthopaedics |
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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. |
first_indexed | 2024-03-08T04:58:39Z |
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id | doaj.art-97420117af4d4e6fb8f635d96fa9b725 |
institution | Directory Open Access Journal |
issn | 2197-1153 |
language | English |
last_indexed | 2024-03-08T04:58:39Z |
publishDate | 2022-01-01 |
publisher | Wiley |
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series | Journal of Experimental Orthopaedics |
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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