Tendon 3D Scaffolds Establish a Tailored Microenvironment Instructing Paracrine Mediated Regenerative Amniotic Epithelial Stem Cells Potential
Tendon tissue engineering aims to develop effective implantable scaffolds, with ideally the native tissue’s characteristics, able to drive tissue regeneration. This research focused on fabricating tendon-like PLGA 3D biomimetic scaffolds with highly aligned fibers and verifying their influence on th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/10/2578 |
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| author | Valentina Russo Mohammad El Khatib Giuseppe Prencipe Annunziata Mauro Oriana Di Giacinto Arlette A. Haidar-Montes Fanny Pulcini Beatrice Dufrusine Adrián Cerveró-Varona Melisa Faydaver Chiara Di Berardino Enrico Dainese Paolo Berardinelli Matthias Schnabelrauch Barbara Barboni |
| author_facet | Valentina Russo Mohammad El Khatib Giuseppe Prencipe Annunziata Mauro Oriana Di Giacinto Arlette A. Haidar-Montes Fanny Pulcini Beatrice Dufrusine Adrián Cerveró-Varona Melisa Faydaver Chiara Di Berardino Enrico Dainese Paolo Berardinelli Matthias Schnabelrauch Barbara Barboni |
| author_sort | Valentina Russo |
| collection | DOAJ |
| description | Tendon tissue engineering aims to develop effective implantable scaffolds, with ideally the native tissue’s characteristics, able to drive tissue regeneration. This research focused on fabricating tendon-like PLGA 3D biomimetic scaffolds with highly aligned fibers and verifying their influence on the biological potential of amniotic epithelial stem cells (AECs), in terms of tenodifferentiation and immunomodulation, with respect to fleeces. The produced 3D scaffolds better resemble native tendon tissue, both macroscopically, microscopically, and biomechanically. From a biological point of view, these constructs were able to instruct AECs genotypically and phenotypically. In fact, cells engineered on 3D scaffolds acquired an elongated tenocyte-like morphology; this was different from control AECs, which retained their polygonal morphology. The boosted AECs tenodifferentiation by 3D scaffolds was confirmed by the upregulation of tendon-related genes (<i>SCX</i>, <i>COL1</i> and <i>TNMD</i>) and TNMD protein expression. The produced constructs also prompted AECs’ immunomodulatory potential, both at the gene and paracrine level. This enhanced immunomodulatory profile was confirmed by a greater stimulatory effect on THP-1-activated macrophages. These biological effects have been related to the mechanotransducer YAP activation evidenced by its nuclear translocation. Overall, these results support the biomimicry of PLGA 3D scaffolds, revealing that not only fiber alignment but also scaffold topology provide an in vitro favorable tenodifferentiative and immunomodulatory microenvironment for AECs that could potentially stimulate tendon regeneration. |
| first_indexed | 2024-03-09T20:38:29Z |
| format | Article |
| id | doaj.art-ff017f15dba84a558936305770aeb06c |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T20:38:29Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-ff017f15dba84a558936305770aeb06c2023-11-23T23:05:22ZengMDPI AGBiomedicines2227-90592022-10-011010257810.3390/biomedicines10102578Tendon 3D Scaffolds Establish a Tailored Microenvironment Instructing Paracrine Mediated Regenerative Amniotic Epithelial Stem Cells PotentialValentina Russo0Mohammad El Khatib1Giuseppe Prencipe2Annunziata Mauro3Oriana Di Giacinto4Arlette A. Haidar-Montes5Fanny Pulcini6Beatrice Dufrusine7Adrián Cerveró-Varona8Melisa Faydaver9Chiara Di Berardino10Enrico Dainese11Paolo Berardinelli12Matthias Schnabelrauch13Barbara Barboni14Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, ItalyUnit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, ItalyUnit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, ItalyUnit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, ItalyUnit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, ItalyUnit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, ItalyDepartment of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, ItalyUnit of Biochemistry and Molecular Biology, Faculty of Bioscience and Technology for Food Agriculture and Environment, University of Teramo, 64100 Teramo, ItalyUnit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, ItalyUnit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, ItalyUnit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, ItalyUnit of Biochemistry and Molecular Biology, Faculty of Bioscience and Technology for Food Agriculture and Environment, University of Teramo, 64100 Teramo, ItalyUnit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, ItalyDepartment of Biomaterials, INNOVENT e. V., 07745 Jena, GermanyUnit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, ItalyTendon tissue engineering aims to develop effective implantable scaffolds, with ideally the native tissue’s characteristics, able to drive tissue regeneration. This research focused on fabricating tendon-like PLGA 3D biomimetic scaffolds with highly aligned fibers and verifying their influence on the biological potential of amniotic epithelial stem cells (AECs), in terms of tenodifferentiation and immunomodulation, with respect to fleeces. The produced 3D scaffolds better resemble native tendon tissue, both macroscopically, microscopically, and biomechanically. From a biological point of view, these constructs were able to instruct AECs genotypically and phenotypically. In fact, cells engineered on 3D scaffolds acquired an elongated tenocyte-like morphology; this was different from control AECs, which retained their polygonal morphology. The boosted AECs tenodifferentiation by 3D scaffolds was confirmed by the upregulation of tendon-related genes (<i>SCX</i>, <i>COL1</i> and <i>TNMD</i>) and TNMD protein expression. The produced constructs also prompted AECs’ immunomodulatory potential, both at the gene and paracrine level. This enhanced immunomodulatory profile was confirmed by a greater stimulatory effect on THP-1-activated macrophages. These biological effects have been related to the mechanotransducer YAP activation evidenced by its nuclear translocation. Overall, these results support the biomimicry of PLGA 3D scaffolds, revealing that not only fiber alignment but also scaffold topology provide an in vitro favorable tenodifferentiative and immunomodulatory microenvironment for AECs that could potentially stimulate tendon regeneration.https://www.mdpi.com/2227-9059/10/10/2578tendonbiomimeticscaffoldamniotic epithelial stem cellstenodifferentiationimmunomodulation |
| spellingShingle | Valentina Russo Mohammad El Khatib Giuseppe Prencipe Annunziata Mauro Oriana Di Giacinto Arlette A. Haidar-Montes Fanny Pulcini Beatrice Dufrusine Adrián Cerveró-Varona Melisa Faydaver Chiara Di Berardino Enrico Dainese Paolo Berardinelli Matthias Schnabelrauch Barbara Barboni Tendon 3D Scaffolds Establish a Tailored Microenvironment Instructing Paracrine Mediated Regenerative Amniotic Epithelial Stem Cells Potential Biomedicines tendon biomimetic scaffold amniotic epithelial stem cells tenodifferentiation immunomodulation |
| title | Tendon 3D Scaffolds Establish a Tailored Microenvironment Instructing Paracrine Mediated Regenerative Amniotic Epithelial Stem Cells Potential |
| title_full | Tendon 3D Scaffolds Establish a Tailored Microenvironment Instructing Paracrine Mediated Regenerative Amniotic Epithelial Stem Cells Potential |
| title_fullStr | Tendon 3D Scaffolds Establish a Tailored Microenvironment Instructing Paracrine Mediated Regenerative Amniotic Epithelial Stem Cells Potential |
| title_full_unstemmed | Tendon 3D Scaffolds Establish a Tailored Microenvironment Instructing Paracrine Mediated Regenerative Amniotic Epithelial Stem Cells Potential |
| title_short | Tendon 3D Scaffolds Establish a Tailored Microenvironment Instructing Paracrine Mediated Regenerative Amniotic Epithelial Stem Cells Potential |
| title_sort | tendon 3d scaffolds establish a tailored microenvironment instructing paracrine mediated regenerative amniotic epithelial stem cells potential |
| topic | tendon biomimetic scaffold amniotic epithelial stem cells tenodifferentiation immunomodulation |
| url | https://www.mdpi.com/2227-9059/10/10/2578 |
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