title: Surface delivery of tunable doses of BMP-2 from an adaptable polymeric scaffold induces volumetric bone regeneration.
abstract: The rapid and effective bone regeneration of large non-healing defects remains challenging. Bioactive proteins, such as bone morphogenetic protein (BMP)-2, are proved their osteoinductivity, but their clinical use is currently limited to collagen as biomaterial. Being able to deliver BMP-2 from any other biomaterial would broaden its clinical use. This work presents a novel means for repairing a critical size volumetric bone femoral defect in the rat by combining a osteoinductive surface coating (2D) to a polymeric scaffold (3D hollow tube) made of commercially-available PLGA. Using a polyelectrolyte film as BMP-2 carrier, we tune the amount of BMP-2 loaded in and released from the polyelectrolyte film coating over a large extent by controlling the film crosslinking level and initial concentration of BMP-2 in solution. Using microcomputed tomography and quantitative analysis of the regenerated bone growth kinetics, we show that the amount of newly formed bone and kinetics can be modulated: an effective and fast repair was obtained in 1-2 weeks in the best conditions, including complete defect bridging, formation of vascularized and mineralized bone tissue. Histological staining and high-resolution computed tomography revealed the presence of bone regeneration inside and around the tube with spatially distinct organization for trabecular-like and cortical bones. The amount of cortical bone and its thickness increased with the BMP-2 dose. In view of the recent developments in additive manufacturing techniques, this surface-coating technology may be applied in combination with various types of polymeric or metallic scaffolds to offer new perspectives of bone regeneration in personalized medicine.
authors.affiliation: CNRS, UMR 5628, LMGP, 3 parvis Louis Néel, F-38016, Grenoble, France; Université de Grenoble Alpes, LMGP, 3 parvis Louis Néel, F-38016, Grenoble, France; Service de chirurgie plastique et maxillo-faciale, Centre Hospitalier Universitaire de Grenoble, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Bouyer
authors.affiliation: CNRS, UMR 5628, LMGP, 3 parvis Louis Néel, F-38016, Grenoble, France; Université de Grenoble Alpes, LMGP, 3 parvis Louis Néel, F-38016, Grenoble, France.
authors.forename: Raphael
authors.initials: R
authors.lastname: Guillot
authors.affiliation: INSERM U1209, Institut Albert Bonniot, F-38000, Grenoble, France; Université Grenoble Alpes, Institut Albert Bonniot, F-38000, Grenoble, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lavaud
authors.affiliation: CNRS, UMR 5628, LMGP, 3 parvis Louis Néel, F-38016, Grenoble, France; Université de Grenoble Alpes, LMGP, 3 parvis Louis Néel, F-38016, Grenoble, France.
authors.forename: Cedric
authors.initials: C
authors.lastname: Plettinx
authors.affiliation: Université de Lyon, CREATIS, CNRS UMR5220, Inserm U1044, INSA-Lyon, Université Claude Bernard Lyon 1, France; ESRF, The European Synchrotron, CS 40220, 38043, Grenoble, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Olivier
authors.affiliation: Unité médico-technique d'Histologie Cytologie expérimentale, Faculté de Médecine, Université Joseph Fourier, 38700, La Tronche, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Curry
authors.affiliation: Unité médico-technique d'Histologie Cytologie expérimentale, Faculté de Médecine, Université Joseph Fourier, 38700, La Tronche, France; Département d'Anatomie et Cytologie Pathologique, Institut de biologie et de pathologie, Centre Hospitalier Universitaire de Grenoble, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Boutonnat
authors.affiliation: INSERM U1209, Institut Albert Bonniot, F-38000, Grenoble, France; Université Grenoble Alpes, Institut Albert Bonniot, F-38000, Grenoble, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Coll
authors.affiliation: Université de Lyon, CREATIS, CNRS UMR5220, Inserm U1044, INSA-Lyon, Université Claude Bernard Lyon 1, France; ESRF, The European Synchrotron, CS 40220, 38043, Grenoble, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Peyrin
authors.affiliation: INSERM U1209, Institut Albert Bonniot, F-38000, Grenoble, France; Université Grenoble Alpes, Institut Albert Bonniot, F-38000, Grenoble, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Josserand
authors.affiliation: INSERM U1209, Institut Albert Bonniot, F-38000, Grenoble, France; Service de chirurgie maxillo-faciale, Centre Hospitalier Annecy Genevois, 1 avenue de l'hôpital, 74370, Epagny Metz-Tessy, France. Electronic address: gbettega@ch-annecygenevois.fr.
authors.forename: Georges
authors.initials: G
authors.lastname: Bettega
authors.affiliation: CNRS, UMR 5628, LMGP, 3 parvis Louis Néel, F-38016, Grenoble, France; Université de Grenoble Alpes, LMGP, 3 parvis Louis Néel, F-38016, Grenoble, France. Electronic address: catherine.picart@grenoble-inp.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Picart
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000737:chemistry; D001861:Bone Regeneration / Q000187:drug effects* / Q000502:physiology; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D005264:Femoral Fractures / Q000503:physiopathology* / Q000628:therapy*; D017102:Fracture Healing / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties; D054457:Tissue Scaffolds; D016896:Treatment Outcome
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D003692:Delayed-Action Preparations
keywords: Biomedical engineering; Bone morphogenetic proteins; Functional coatings; Orthopedic materials; Tissue engineering