title: A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration.
abstract: 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.
authors.affiliation: INSERM, UMR 1109, Osteoarticular and Dental Regenerative Nanomedicine Laboratory, FMTS, Faculté de Médecine, Strasbourg, France ; Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
authors.forename: Sandy
authors.initials: S
authors.lastname: Eap
authors.affiliation: INSERM, UMR 1109, Osteoarticular and Dental Regenerative Nanomedicine Laboratory, FMTS, Faculté de Médecine, Strasbourg, France ; Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France ; Department of Chemical Engineering, Aragon Nanoscience Institute, University of Zaragoza, Zaragoza, Spain.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Keller
authors.affiliation: INSERM, UMR 1109, Osteoarticular and Dental Regenerative Nanomedicine Laboratory, FMTS, Faculté de Médecine, Strasbourg, France ; Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
authors.forename: Jessica
authors.initials: J
authors.lastname: Schiavi
authors.affiliation: INSERM, UMR 1109, Osteoarticular and Dental Regenerative Nanomedicine Laboratory, FMTS, Faculté de Médecine, Strasbourg, France ; Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Huck
authors.affiliation: CNRS (National Center for Scientific Research), ICS (Charles Sadron Institute), Strasbourg, France.
authors.forename: Leandro
authors.initials: L
authors.lastname: Jacomine
authors.affiliation: INSERM, UMR 1109, Osteoarticular and Dental Regenerative Nanomedicine Laboratory, FMTS, Faculté de Médecine, Strasbourg, France ; Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Fioretti
authors.affiliation: CNRS (National Center for Scientific Research), ICS (Charles Sadron Institute), Strasbourg, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Gauthier
authors.affiliation: INSERM, UMR 1109, Osteoarticular and Dental Regenerative Nanomedicine Laboratory, FMTS, Faculté de Médecine, Strasbourg, France ; Department of Chemical Engineering, Aragon Nanoscience Institute, University of Zaragoza, Zaragoza, Spain ; Networking Research Center of Bioengineering, Biomaterials and Nanomedicine, Zaragoza, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Sebastian
authors.affiliation: INSERM, UMR 1109, Osteoarticular and Dental Regenerative Nanomedicine Laboratory, FMTS, Faculté de Médecine, Strasbourg, France ; Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Schwinté
authors.affiliation: INSERM, UMR 1109, Osteoarticular and Dental Regenerative Nanomedicine Laboratory, FMTS, Faculté de Médecine, Strasbourg, France ; Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Benkirane-Jessel
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000494:pharmacology; D001861:Bone Regeneration / Q000187:drug effects*; D018786:Bone Substitutes / Q000737:chemistry / Q000494:pharmacology; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D057139:Nanofibers / Q000737:chemistry*; D019736:Prostheses and Implants; D012886:Skull / Q000293:injuries
chemical_list: D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; D048271:Chitosan
keywords: BMP-7; electrospun nanofibers implant; nanocontainers of growth factors; regenerative nanomedicine