A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration

Sandy Eap,1,2,* Laetitia Keller,1–3,* Jessica Schiavi,1,2 Olivier Huck,1,2 Leandro Jacomine,4 Florence Fioretti,1,2 Christian Gauthier,4 Victor Sebastian,1,3,5 Pascale Schwinté,1,2 Nadia Benkirane-Jessel1,21INSERM, UMR 1109, Osteoarticular and Dental Regenerative Nanomedicine L...

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Autores principales: Eap S, Keller L, Schiavi J, Huck O, Jacomine L, Fioretti F, Gauthier C, Sebastian V, Schwinté P, Benkirane-Jessel N
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Publicado: Dove Medical Press 2015
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spelling oai:doaj.org-article:37b75a29960d47ba8707a5bdebd2136c2021-12-02T07:44:04ZA living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration1178-2013https://doaj.org/article/37b75a29960d47ba8707a5bdebd2136c2015-02-01T00:00:00Zhttp://www.dovepress.com/a-living-thick-nanofibrous-implant-bifunctionalized-with-active-growth-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Sandy Eap,1,2,* Laetitia Keller,1–3,* Jessica Schiavi,1,2 Olivier Huck,1,2 Leandro Jacomine,4 Florence Fioretti,1,2 Christian Gauthier,4 Victor Sebastian,1,3,5 Pascale Schwinté,1,2 Nadia Benkirane-Jessel1,21INSERM, UMR 1109, Osteoarticular and Dental Regenerative Nanomedicine Laboratory, FMTS, Faculté de Médecine, Strasbourg, France; 2Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France; 3Department of Chemical Engineering, Aragon Nanoscience Institute, University of Zaragoza, Zaragoza, Spain; 4CNRS (National Center for Scientific Research), ICS (Charles Sadron Institute), Strasbourg, France; 5Networking Research Center of Bioengineering, Biomaterials and Nanomedicine, Zaragoza, Spain*These authors contributed equally to this workAbstract: New-generation implants focus on robust, durable, and rapid tissue regeneration to shorten recovery times and decrease risks of postoperative complications for patients. Herein, we describe a new-generation thick nanofibrous implant functionalized with active containers of growth factors and stem cells for regenerative nanomedicine. A thick electrospun poly(ε-caprolactone) nanofibrous implant (from 700 µm to 1 cm thick) was functionalized with chitosan and bone morphogenetic protein BMP-7 as growth factor using layer-by-layer technology, producing fish scale-like chitosan/BMP-7 nanoreservoirs. This extracellular matrix-mimicking scaffold enabled in vitro colonization and bone regeneration by human primary osteoblasts, as shown by expression of osteocalcin, osteopontin, and bone sialoprotein (BSPII), 21 days after seeding. In vivo implantation in mouse calvaria defects showed significantly more newly mineralized extracellular matrix in the functionalized implant compared to a bare scaffold after 30 days’ implantation, as shown by histological scanning electron microscopy/energy dispersive X-ray microscopy study and calcein injection. We have as well bifunctionalized our BMP-7 therapeutic implant by adding human mesenchymal stem cells (hMSCs). The activity of this BMP-7-functionalized implant was again further enhanced by the addition of hMSCs to the implant (living materials), in vivo, as demonstrated by the analysis of new bone formation and calcification after 30 days’ implantation in mice with calvaria defects. Therefore, implants functionalized with BMP-7 nanocontainers associated with hMSCs can act as an accelerator of in vivo bone mineralization and regeneration.Keywords: regenerative nanomedicine, electrospun nanofibers implant, nanocontainers of growth factors, BMP-7Eap SKeller LSchiavi JHuck OJacomine LFioretti FGauthier CSebastian VSchwinté PBenkirane-Jessel NDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 1061-1075 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Eap S
Keller L
Schiavi J
Huck O
Jacomine L
Fioretti F
Gauthier C
Sebastian V
Schwinté P
Benkirane-Jessel N
A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration
description Sandy Eap,1,2,* Laetitia Keller,1–3,* Jessica Schiavi,1,2 Olivier Huck,1,2 Leandro Jacomine,4 Florence Fioretti,1,2 Christian Gauthier,4 Victor Sebastian,1,3,5 Pascale Schwinté,1,2 Nadia Benkirane-Jessel1,21INSERM, UMR 1109, Osteoarticular and Dental Regenerative Nanomedicine Laboratory, FMTS, Faculté de Médecine, Strasbourg, France; 2Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France; 3Department of Chemical Engineering, Aragon Nanoscience Institute, University of Zaragoza, Zaragoza, Spain; 4CNRS (National Center for Scientific Research), ICS (Charles Sadron Institute), Strasbourg, France; 5Networking Research Center of Bioengineering, Biomaterials and Nanomedicine, Zaragoza, Spain*These authors contributed equally to this workAbstract: New-generation implants focus on robust, durable, and rapid tissue regeneration to shorten recovery times and decrease risks of postoperative complications for patients. Herein, we describe a new-generation thick nanofibrous implant functionalized with active containers of growth factors and stem cells for regenerative nanomedicine. A thick electrospun poly(ε-caprolactone) nanofibrous implant (from 700 µm to 1 cm thick) was functionalized with chitosan and bone morphogenetic protein BMP-7 as growth factor using layer-by-layer technology, producing fish scale-like chitosan/BMP-7 nanoreservoirs. This extracellular matrix-mimicking scaffold enabled in vitro colonization and bone regeneration by human primary osteoblasts, as shown by expression of osteocalcin, osteopontin, and bone sialoprotein (BSPII), 21 days after seeding. In vivo implantation in mouse calvaria defects showed significantly more newly mineralized extracellular matrix in the functionalized implant compared to a bare scaffold after 30 days’ implantation, as shown by histological scanning electron microscopy/energy dispersive X-ray microscopy study and calcein injection. We have as well bifunctionalized our BMP-7 therapeutic implant by adding human mesenchymal stem cells (hMSCs). The activity of this BMP-7-functionalized implant was again further enhanced by the addition of hMSCs to the implant (living materials), in vivo, as demonstrated by the analysis of new bone formation and calcification after 30 days’ implantation in mice with calvaria defects. Therefore, implants functionalized with BMP-7 nanocontainers associated with hMSCs can act as an accelerator of in vivo bone mineralization and regeneration.Keywords: regenerative nanomedicine, electrospun nanofibers implant, nanocontainers of growth factors, BMP-7
format article
author Eap S
Keller L
Schiavi J
Huck O
Jacomine L
Fioretti F
Gauthier C
Sebastian V
Schwinté P
Benkirane-Jessel N
author_facet Eap S
Keller L
Schiavi J
Huck O
Jacomine L
Fioretti F
Gauthier C
Sebastian V
Schwinté P
Benkirane-Jessel N
author_sort Eap S
title A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration
title_short A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration
title_full A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration
title_fullStr A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration
title_full_unstemmed A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration
title_sort living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/37b75a29960d47ba8707a5bdebd2136c
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