Differences in interleukin-1 response between engineered and native cartilage

Unlike native cartilage explants that are used in autologous tissue transfer procedures, engineered cartilage constructs are typically highly fragile when first formed and must rely on cellular activity to develop over time. However, inflammatory cytokines such as interleukin-1alpha (IL-1alpha) are often present in target joints and may interfere with this development process. Herein we examine to what extent nascent engineered tissue is susceptible to chemical perturbations by IL-1alpha (10 ng/mL), especially when compared to native explants, and whether in vitro preconditioning may promote sufficient integrity to lessen this impact. The studies were carried out using a chemically defined medium supplemented with or without the antiinflammatory steroid dexamethasone. We find that engineered tissue (bovine chondrocytes in agarose hydrogel) at early time points (days 0 and 14) does not grow when exposed to the cytokine even temporarily, but both bovine explants and more developed engineered tissue (day 28) are able to withstand the same exposure without degradation of properties. We argue therefore that some in vitro preconditioning may be necessary to promote both sufficient mechanical integrity and the chemical fortitude without which insufficiently developed engineered constructs will not survive the harsh mechanochemical environment within the joint.