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3D Osteochondral Model
Special Programs
A new dimension in testing
An osteochondral model has been developed using a 3D scaffold to create a defined bi-layer construct (Figure 1A). Bioprinted mesenchymal stem cells (MSCs) are differentiated in the 3D environment to mature into chondrocytes (Figure 1C). Osteochondral co-cultures are then created bioprinting MSC derived osteoblasts onto the bioprinted chondrocyte layer (Figure 1B). The mature model can be stimulated and respond to inflammatory cytokines, resulting in a loss of chondral layer proteoglycan content specifically aggrecan (Figure 1D).
Furthermore the osteochondral co-cultures present an osteoarthritis like phenotype with release of disease associated proteins such as matrix metalloprotease-9 (MMP9), MMP13 and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) into co-culture supernatant (Figure 2). The disease like phenotype also results in the general increase of MMP activity as shown in Figure 3. This response can be modified through treatment of models with molecules such as a pan metalloprotease inhibitor.
Furthermore the osteochondral co-cultures present an osteoarthritis like phenotype with release of disease associated proteins such as matrix metalloprotease-9 (MMP9), MMP13 and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) into co-culture supernatant (Figure 2). The disease like phenotype also results in the general increase of MMP activity as shown in Figure 3. This response can be modified through treatment of models with molecules such as a pan metalloprotease inhibitor.
Figure 2. Concentrations of MMP9, MMP13 and ADAMTS4 increase following cytokine stimulation.
Figure 3. Metalloproteinase activity assay before and after cytokine stimulation alongside PAN MMP activity inhibitor.
Figure 1A) H&E of 3D Osteochondral Model. B) Aggrecan and osteocalcin staining demonstrates mature chondrocyte and osteocyte differentiation. C) Aggrecan staining before stimulation and D) Aggrecan staining after stimulation.
