Manufacturing of tricalcium phosphate bone tissue engineered orthopedic implants by selective laser sintering – OrthoFLase

RESUME: The proposed project aims at developing an innovative approach for the treatment of large bone
defects using advances in material technology. It aims to improve the autonomy and quality of life for the orthopaedic
patient by helping avoid the morbidity associated with autologous bone graft harvesting. A new innovative process of
additive manufacturing by laser fusion of tri-calcium phosphate sintering will be used to fabricate scaffolds for use in
orthopaedic surgery. Complex architectures required for engineering efficient bone constructs are impossible to obtain by
current methods for shaping ceramics such as moulding, injection or milling. Laser fusion technology provides an
attractive and efficient solution to produce implants without the drawbacks of current techniques. Due to the precision of
the laser, precise control of the shape and macroporosity parameters (i.e. porosity size, morphology, distribution) are
obtained using the layer-by-layer deposition method. Nowadays, this process constitutes the most advanced method for
manufacturing custom—made engineered bone constructs with an internal optimized structure that favours vascular
invasion and bone formation. The final properties of ceramics (physical, mechanical, chemical, and biological) will depend
largely on the adjustment of the powder properties, (i.e. their ability to be layered and interact with the laser in a controlled
and reproducible manner). The physico-chemical characteristics of powders having the best responsiveness while
maintaining good properties (i.e. % phases, topography ...) and the optimum settings of the laser and its environment will
be identified. Optimized ceramics will then be assessed for their cytocompatibility in vitro. Their biocompatibility and
osteoconductivlty will be evaluated in vivo in femoral condyle defects in rabbits. Three-dimmensional shaping and macro-
porosity of the tissue construct will be achieved by refining laser parameters, layer by layer, as well as optimizing the
gaseous and thermal variables. The fabricated bioceramics will then be characterised and tested biologically. A first study
will aim at optimizing the architecture of 3D implants by assessing the influence of pore volume and distribution of the
porosity within the implant. A second study will be designed to test the effects of the repartition of the porosity to determine
the origin of cell recruitment and newly formed bone. Subsequently, the scaffolds will be seeded with mesenchymal stem
cells to improve osteogenesis and tested in vivo in a rabbit animal model. Lastly, the biological functionality of the
optimized bone constructs seeded with mesenchymal stem cells will be assessed in a load-bearing situation in bone defects of clinically relevant size in sheep. Using this processing, tissue contructs custom shaped to the patient defect and having optimized macro-porosities will be fabricated using rapid prototyping technology.