title: Low-dose BMP-2 and MSC dual delivery onto coral scaffold for critical-size bone defect regeneration in sheep.
abstract: Tissue-engineered constructs (TECs) combining resorbable calcium-based scaffolds and mesenchymal stem cells (MSCs) have the capability to regenerate large bone defects. Inconsistent results have, however, been observed, with a lack of osteoinductivity as a possible cause of failure. This study aimed to evaluate the impact of the addition of low-dose bone morphogenetic protein-2 (BMP-2) to MSC-coral-TECs on the healing of clinically relevant segmental bone defects in sheep. Coral granules were either seeded with autologous MSCs (bone marrow-derived) or loaded with BMP-2. A 25-mm-long metatarsal bone defect was created and stabilized with a plate in 18 sheep. Defects were filled with one of the following TECs: (i) BMP (n = 5); (ii) MSC (n = 7); or (iii) MSC-BMP (n = 6). Radiographic follow-up was performed until animal sacrifice at 4 months. Bone formation and scaffold resorption were assessed by micro-CT and histological analysis. Bone union with nearly complete scaffold resorption was observed in 1/5, 2/7, and 3/6 animals, when BMP-, MSC-, and MSC-BMP-TECs were implanted, respectively. The amount of newly formed bone was not statistically different between groups: 1074 mm3[970-2478 mm3], 1155 mm3[970-2595 mm3], and 2343 mm3[931-3276 mm3] for BMP-, MSC-, and MSC-BMP-TECs, respectively. Increased scaffold resorption rate using BMP-TECs was the only potential side effect observed. In conclusion, although the dual delivery of MSCs and BMP-2 onto a coral scaffold further increased bone formation and bone union when compared to single treatment, results were non-significant. Only 50% of the defects healed, demonstrating the need for further refinement of this strategy before clinical use. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2637-2645, 2017.
authors.affiliation: Laboratoire de Bioingénierie et Bioimagerie Ostéo-Articulaire (B2OA-UMR CNRS 7052) Université Paris Diderot, 10 Avenue de Verdun, 75010, Paris, France.|Ecole Nationale Vétérinaire d'Alfort (Université Paris-Est), 7 avenue du général de Gaulle, 94704, Maisons-Alfort Cedex, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Decambron
authors.affiliation: Laboratoire de Bioingénierie et Bioimagerie Ostéo-Articulaire (B2OA-UMR CNRS 7052) Université Paris Diderot, 10 Avenue de Verdun, 75010, Paris, France.|Ecole Nationale Vétérinaire d'Alfort (Université Paris-Est), 7 avenue du général de Gaulle, 94704, Maisons-Alfort Cedex, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Fournet
authors.affiliation: Laboratoire de Bioingénierie et Bioimagerie Ostéo-Articulaire (B2OA-UMR CNRS 7052) Université Paris Diderot, 10 Avenue de Verdun, 75010, Paris, France.
authors.forename: Morad
authors.initials: M
authors.lastname: Bensidhoum
authors.affiliation: Laboratoire de Bioingénierie et Bioimagerie Ostéo-Articulaire (B2OA-UMR CNRS 7052) Université Paris Diderot, 10 Avenue de Verdun, 75010, Paris, France.|Ecole Nationale Vétérinaire d'Alfort (Université Paris-Est), 7 avenue du général de Gaulle, 94704, Maisons-Alfort Cedex, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Manassero
authors.affiliation: Hopital Cochin, Service d'orthopédie et chirurgie du rachis, 27 Rue du Faubourg Saint-Jacques, 75014, Paris, France.|Clinique Arago, 187 Rue Raymond Losserand, 75014, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Sailhan
authors.affiliation: Laboratoire de Bioingénierie et Bioimagerie Ostéo-Articulaire (B2OA-UMR CNRS 7052) Université Paris Diderot, 10 Avenue de Verdun, 75010, Paris, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Petite
authors.affiliation: Laboratoire de Bioingénierie et Bioimagerie Ostéo-Articulaire (B2OA-UMR CNRS 7052) Université Paris Diderot, 10 Avenue de Verdun, 75010, Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Logeart-Avramoglou
authors.affiliation: Laboratoire de Bioingénierie et Bioimagerie Ostéo-Articulaire (B2OA-UMR CNRS 7052) Université Paris Diderot, 10 Avenue de Verdun, 75010, Paris, France.|Ecole Nationale Vétérinaire d'Alfort (Université Paris-Est), 7 avenue du général de Gaulle, 94704, Maisons-Alfort Cedex, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Viateau
mesh_terms: D000818:Animals; D037421:Anthozoa; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D001861:Bone Regeneration / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D005260:Female; D048091:Guided Tissue Regeneration; D045164:Mesenchymal Stem Cell Transplantation; D008682:Metatarsal Bones; D012756:Sheep; D054457:Tissue Scaffolds
chemical_list: D055396:Bone Morphogenetic Protein 2
keywords: BMP-2; bone union; dual delivery; mesenchymal stem cells; sheep; tissue engineering