title: The performance of poly-epsilon-caprolactone scaffolds in a rabbit femur model with and without autologous stromal cells and BMP4.
abstract: The ability of a cellular construct to guide and promote tissue repair strongly relies on three components, namely, cell, scaffold and growth factors. We aimed to investigate the osteopromotive properties of cellular constructs composed of poly-epsilon-caprolactone (PCL) and rabbit bone marrow stromal cells (BMSCs), or BMSCs engineered to express bone morphogenetic protein 4 (BMP4). Highly porous biodegradable PCL scaffolds were obtained via phase inversion/salt leaching technique. BMSCs and transfected BMSCs were seeded within the scaffolds by using an alternate flow perfusion system and implanted into non-critical size defects in New Zealand rabbit femurs. In vivo biocompatibility, osteogenic and angiogenic effects induced by the presence of scaffolds were assessed by histology and histomorphometry of the femurs, retrieved 4 and 8 weeks after surgery. PCL without cells showed scarce bone formation at the scaffold-bone interface (29% bone/implant contact and 62% fibrous tissue/implant contact) and scarce PCL resorption (16%). Conversely, PCL seeded with autologous BMSCs stimulated new tissue formation into the macropores of the implant (20%) and neo-tissue vascularization. Finally, the BMP4-expressing BMSCs strongly favoured osteoinductivity of cellular constructs, as demonstrated by a more extensive bone/scaffold contact.
authors.affiliation: Laboratory for Pathophysiology of Orthopaedic Implants, Istituti Ortopedici Rizzoli, Via di Barbiano 1/10, 40136, Bologna, Italy. lucia.savarino@ior.it
authors.forename: L
authors.initials: L
authors.lastname: Savarino
authors.forename: N
authors.initials: N
authors.lastname: Baldini
authors.forename: M
authors.initials: M
authors.lastname: Greco
authors.forename: O
authors.initials: O
authors.lastname: Capitani
authors.forename: S
authors.initials: S
authors.lastname: Pinna
authors.forename: S
authors.initials: S
authors.lastname: Valentini
authors.forename: B
authors.initials: B
authors.lastname: Lombardo
authors.forename: M T
authors.initials: MT
authors.lastname: Esposito
authors.forename: L
authors.initials: L
authors.lastname: Pastore
authors.forename: L
authors.initials: L
authors.lastname: Ambrosio
authors.forename: S
authors.initials: S
authors.lastname: Battista
authors.forename: F
authors.initials: F
authors.lastname: Causa
authors.forename: S
authors.initials: S
authors.lastname: Zeppetelli
authors.forename: V
authors.initials: V
authors.lastname: Guarino
authors.forename: P A
authors.initials: PA
authors.lastname: Netti
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002208:Caproates / Q000737:chemistry*; D017690:Cell Transplantation / Q000379:methods; D005269:Femur / Q000254:growth & development / Q000378:metabolism / Q000601:surgery*; D005822:Genetic Vectors / Q000235:genetics; D007783:Lactones / Q000737:chemistry*; D010012:Osteogenesis; D011108:Polymers / Q000737:chemistry; D011817:Rabbits; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods; D014162:Transfection; D014182:Transplantation, Autologous
chemical_list: D001672:Biocompatible Materials; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002208:Caproates; D007783:Lactones; D011108:Polymers; C121056:caprolactone