Bone
B1:1 Definition of gel/HA scaffold
The scaffold for the bone repair optimization/monitoring will be defined, prepared, evaluated in cell culture and shipped sterile to UCL. Injectable carriers of self assembled peptides and gel forming hyaluronan will be combined with bioactive ceramics and growth factors. Special emphasis will be on preparation of ceramics with variable shape, size and composition.
B1:2 Definition of structural scaffold
Preshaped scaffold for the repair of a structurally defined bone defects will be prepared having longitudinal holes. The material will be based on resorbable bioceramics.
B1:3 Optimization/ monitoring bone formation in rat
Careful monitoring with time of bone formation in the animal model will be performed combining histology, mCT and TEM to simultaneously see vascular in growth, matrix/HA degradation, new HA deposition along with full bone formation. This work will start with an optimization of HA loading and type as well as gel crosslink density.
B1:4 Bone repair in rat
A segmental defect in the rat tibia will be prepared and the structural scaffold from B1:2 will be used to bridge the gap for bone regeneration. Repair with the scaffold only will be compared with scaffold filled with hya gel and hya gel loaded with BMP-2.
B1:5 Cell assisted bone repair
Larger defects, irradiated patients and sites with limited supply of stem cells might require addition of external cells. Injectable in situ forming scaffolds will be colonized with stem cells to improve their bone formation induction ability. Gel formation parameters will be varied in order to maintain cell viability after gelation. Cell metabolic activity, proliferation and differentiation towards bone phenotype will be assessed. Finally, in the system injectable scaffold/cells will be tested as far as its ability to improve bone regeneration, comparing to the same system without the cells. The scaffold optimization will be carried out at UU and the cell colonization and biological evaluation at INEB.
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