Cartilage
C1:1 Definition of scaffolds
The scaffold for the pig cartilage repair model will be defined, prepared, evaluated in cell culture and shipped sterile to Groningen. Carriers of self-assembled peptides and gel forming hyaluronan will be combined with growth factors.
C1:2 Evaluation of scaffolds with MSCs in cell culture
Since the purpose of the project is to develop an injectable scaffold material for cartilage formation sub-periosteal, different formulations of self-assembled peptides and gel forming HYA will be tested with mesenchymal stromal cells from bone marrow or subcutaneous fat to find formulations with the highest chondrogenic potential, which will be evaluated in an animal model. We will look for a formulation which will steer the differentiation of MSCs into the chondrogenic lineage, similar as has been shown by the group of S. Stupp for stem cells which were directed towards neurogenic differentiation instead of differentiation into astrocytes. MSCs will be cultured in the scaffolds and chondrogenesis will be evaluated
C1:3 Cartilage formation in animal
The materials with a proven chondrogenic potential will be injected sub-perioteal on different locations in a pig model. Cartilage formation will be evaluated in time for maximally 30 days. This experiment should result in the optimal period for harvesting the cartilage for transplantation in an osteochondral lesion (C1:4). Six pigs will be used. Each pig will receive all formulations (maximally 6). At 1, 2 and 4 weeks follow up 2 pigs will be sacrificed and cartilage formation will be evaluated.
C1:4 Cartilage repair in animal
Cartilage formation will be induced by injecting the scaffold material underneath the periosteum. At a given time the formed cartilage tissue will be harvested and transplanted into osteochondral lesions in the knee joint (femoral condyle). The thickness of the harvested cartilage will be measured, then a drill hole with the same depth will be made and the cartilage will be press fit implanted. Joint surface repair will be evaluated at 2 weeks, 3 and 6 months.
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