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Calcif Tissue Int. 2016 Aug;99(2):209-23. doi: 10.1007/s00223-016-0140-8. Epub 2016 Apr 13.

In Vivo Bone Formation Within Engineered Hydroxyapatite Scaffolds in a Sheep Model.

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Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, Milan, Italy.
Mouse and Animal Pathology Laboratory, Fondazione Filarete, Milan, Italy.
Dipartimento di Elettronica, Informazione e Bioingegneria (DEIB), Politecnico di Milano, Milan, Italy.
Department of Veterinary Sciences and Public Health, University of Milan, Milan, Italy.
Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, Milan, Italy.
Regenerative Medicine Technologies Lab, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland.
Swiss Institute of Regenerative Medicine (SIRM), Lugano, Switzerland.
Fondazione Cardiocentro Ticino, Lugano, Switzerland.


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.


Bone graft; Dynamic culture; Femur; Mesenchymal stem cells; Ovine model; Tibia

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