title: Large defect-tailored composite scaffolds for in vivo bone regeneration.
abstract: The discovery of new strategies to repair large segmental bone defects is currently an open challenge for worldwide clinicians. In the treatment of critical-sized bone defects, an alternative strategy to traditional bone grafting is always more frequently the use of tailor-made scaffolds modelled on the final size and shape of the implant site. Here, poly-ε-caprolactone-based composite scaffolds including poly-L-lactic acid continuous fibres and hyaluronan derivates (i.e. HYAFF11®) have been investigated for the peculiar 3D architecture characterized by interconnected macroporous networks and tunable mechanical properties. Composite scaffolds were immersed in simulated body fluid solution in order to support in vivo tissue in-growth. Scaffolds loaded with autologous cells (bone marrow stromal cells) plus platelet-rich plasma and osteoconductive protein such bone morphogenetic protein-7 were also tested to evaluate eventual enhancement in bone regeneration. The morphological and mechanical properties of poly-L-lactic acid-reinforced composite scaffolds have been studied to identify the optimal scaffold design to match the implant-site requirements of sheep metatarsal defects. Dynamic mechanical tests allowed to underline the viscoelastic response of the scaffold - resulting in elastic moduli from 2.5 to 1.3 MPa, suitable to temporarily support the structural function of damaged bone tissue. In vivo preliminary investigations in a sheep model of metatarsus shaft defect also showed the attitude of the scaffold to promote osteogenesis, preferentially in association with bone marrow stromal cell and platelet-rich plasma, even if the highest amount of mature bone was reached in the case of scaffold loaded with human bone morphogenetic protein-7 released via hydrolytic degradation of HYAFF11® phases in the implant site.
authors.affiliation: Institute for Polymers, Composites and Biomaterials, National Research Council of Italy, Napoli, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ronca
authors.affiliation: Institute for Polymers, Composites and Biomaterials, National Research Council of Italy, Napoli, Italy vguarino@unina.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Guarino
authors.affiliation: Institute for Polymers, Composites and Biomaterials, National Research Council of Italy, Napoli, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Raucci
authors.affiliation: Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies-Department RIT Rizzoli, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Salamanna
authors.affiliation: Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies-Department RIT Rizzoli, Rizzoli Orthopaedic Institute, Bologna, Italy Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Martini
authors.affiliation: Institute for Polymers, Composites and Biomaterials, National Research Council of Italy, Napoli, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Zeppetelli
authors.affiliation: Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies-Department RIT Rizzoli, Rizzoli Orthopaedic Institute, Bologna, Italy Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Fini
authors.affiliation: II Clinic - Biomechanics Laboratory, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Elisaveta
authors.initials: E
authors.lastname: Kon
authors.affiliation: II Clinic - Biomechanics Laboratory, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Filardo
authors.affiliation: II Clinic - Biomechanics Laboratory, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Maurilio
authors.initials: M
authors.lastname: Marcacci
authors.affiliation: Institute for Polymers, Composites and Biomaterials, National Research Council of Italy, Napoli, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ambrosio
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism; D001861:Bone Regeneration; D001842:Bone and Bones / Q000473:pathology; D005260:Female; D006358:Hot Temperature; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D010012:Osteogenesis; D011091:Polyesters / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D011312:Pressure; D012756:Sheep; D013314:Stress, Mechanical; D017154:Stromal Cells / Q000166:cytology; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D011091:Polyesters; D011108:Polymers; C016240:polycaprolactone; D019344:Lactic Acid; C033616:poly(lactide)
keywords: Composite scaffolds; bioactivation; bone; in vivo; mechanical properties