title: In Vivo Bone Formation Within Engineered Hydroxyapatite Scaffolds in a Sheep Model.
abstract: Large bone defects still represent a major burden in orthopedics, requiring bone-graft implantation to promote the bone repair. Along with autografts that currently represent the gold standard for complicated fracture repair, the bone tissue engineering offers a promising alternative strategy combining bone-graft substitutes with osteoprogenitor cells able to support the bone tissue ingrowth within the implant. Hence, the optimization of cell loading and distribution within osteoconductive scaffolds is mandatory to support a successful bone formation within the scaffold pores. With this purpose, we engineered constructs by seeding and culturing autologous, osteodifferentiated bone marrow mesenchymal stem cells within hydroxyapatite (HA)-based grafts by means of a perfusion bioreactor to enhance the in vivo implant-bone osseointegration in an ovine model. Specifically, we compared the engineered constructs in two different anatomical bone sites, tibia, and femur, compared with cell-free or static cell-loaded scaffolds. After 2 and 4 months, the bone formation and the scaffold osseointegration were assessed by micro-CT and histological analyses. The results demonstrated the capability of the acellular HA-based grafts to determine an implant-bone osseointegration similar to that of statically or dynamically cultured grafts. Our study demonstrated that the tibia is characterized by a lower bone repair capability compared to femur, in which the contribution of transplanted cells is not crucial to enhance the bone-implant osseointegration. Indeed, only in tibia, the dynamic cell-loaded implants performed slightly better than the cell-free or static cell-loaded grafts, indicating that this is a valid approach to sustain the bone deposition and osseointegration in disadvantaged anatomical sites.
authors.affiliation: Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, Milan, Italy.
authors.forename: A B
authors.initials: AB
authors.lastname: Lovati
authors.affiliation: Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Lopa
authors.affiliation: Mouse and Animal Pathology Laboratory, Fondazione Filarete, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Recordati
authors.affiliation: Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Talò
authors.affiliation: Dipartimento di Elettronica, Informazione e Bioingegneria (DEIB), Politecnico di Milano, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Turrisi
authors.affiliation: Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, Milan, Italy.|Department of Veterinary Sciences and Public Health, University of Milan, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bottagisio
authors.affiliation: Mouse and Animal Pathology Laboratory, Fondazione Filarete, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Losa
authors.affiliation: Mouse and Animal Pathology Laboratory, Fondazione Filarete, Milan, Italy.|Department of Veterinary Sciences and Public Health, University of Milan, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Scanziani
authors.affiliation: Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, Milan, Italy. matteo.moretti@grupposandonato.it.|Regenerative Medicine Technologies Lab, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland. matteo.moretti@grupposandonato.it.|Swiss Institute of Regenerative Medicine (SIRM), Lugano, Switzerland. matteo.moretti@grupposandonato.it.|Fondazione Cardiocentro Ticino, Lugano, Switzerland. matteo.moretti@grupposandonato.it.
authors.forename: M
authors.initials: M
authors.lastname: Moretti
mesh_terms: D000818:Animals; D018786:Bone Substitutes / Q000378:metabolism; D016025:Bone Transplantation / Q000379:methods; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D017886:Durapatite / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D016348:Osseointegration / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology; D012756:Sheep; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds
chemical_list: D018786:Bone Substitutes; D017886:Durapatite
keywords: Bone graft; Dynamic culture; Femur; Mesenchymal stem cells; Ovine model; Tibia