Engineered cartilage maturation regulates cytokine production and interleukin-1beta response

BACKGROUND: Because the injured joint has an actively inflammatory environment, the survival and repair potential of cartilage grafts may be influenced by inflammatory processes. Understanding the interactions of those processes with the graft may lead to concepts for pharmacologic or surgical solutions allowing improved cartilage repair. QUESTIONS/PURPOSES: We asked whether the maturation level of cartilaginous tissues generated in vitro by expanded human articular chondrocytes (HACs) modulate (1) the spontaneous production of cytokines and (2) the response to interleukin (IL)-1beta. METHODS: Twelve pellets/donor prepared with monolayer-expanded HACs (n = 6 donors) were evaluated at six different culture times for mRNA expression (n = 72) and spontaneous baseline release of monocyte chemoattractant protein (MCP)-1, IL-8, and transforming growth factor (TGF)-beta1 (n = 72). We cultured 24 pellets/donor from each of four donors for 1 or 14 days (defined as immature and mature, respectively) and exposed the pellets to IL-1beta for 3 days. MCP-1, IL-8, TGF-beta1, and metalloprotease (MMP)-1 and MMP-13 were quantified in pellets and culture supernatants. RESULTS: By increasing culture time, the spontaneous release of IL-8 and MCP-1 decreased (12.0- and 5.5-fold, respectively), whereas that of TGF-beta1 increased (5.4-fold). As compared with immature pellets, mature pellets responded to IL-1beta by releasing lower amounts of MMP-1 (2.9-fold) and MMP-13 (1.7-fold) and increased levels of IL-8, MCP-1, and TGF-beta1 (1.5-, 5.0-, and 7.5-fold, respectively). IL-8 and MCP-1 promptly returned to baseline on withdrawal of IL-1beta. CONCLUSIONS: Our observations suggest more mature cartilaginous tissues are more resistant to IL-1beta exposure and can activate chemokines required to initiate tissue repair processes. CLINICAL RELEVANCE: The implantation of more mature cartilaginous tissues might provide superior graft survival and improve/accelerate cartilage repair.