Chronic inflammation in biomaterial-induced periprosthetic osteolysis: NF-κB as a therapeutic target.

Biomaterial-induced tissue responses in patients with total joint replacement are associated with the generation of wear particles, which may lead to chronic inflammation and local bone destruction (periprosthetic osteolysis). Inflammatory reactions associated with wear particles are mediated by several important signaling pathways, the most important of which involves the transcription factor NF-κB. NF-κB activation is essential for macrophage recruitment and maturation, as well as the production of pro-inflammatory cytokines and chemokines such as TNF-α, IL-1ß, IL-6 and MCP1. In addition, NF-κB activation contributes to osteoclast differentiation and maturation via RANK/RANKL signaling, which increases bone destruction and reduces bone formation. Targeting individual downstream cytokines directly (such as TNF-α or IL-1ß) may not effectively prevent wear particle induced osteolysis. A more logical upstream therapeutic approach may be provided by direct modulation of the core IκB/IKKα/ß/NF-κB signaling pathway in the local environment. However, the timing, dose and strategy for administration should be considered. Suppression of chronic inflammation via inhibition of NF-κB activity in patients with malfunctioning joint replacements may be an effective strategy to mitigate wear particle induced periprosthetic osteolysis.

Co-culture of adipose derived stem cells and chondrocytes with surface modifying proteins induces enhanced cartilage tissue formation.

OBJECTIVES: Current treatments for focal cartilage defects include osteochondral allograft transplants-a common treatment for large defects and revisions of previously autografted joints. Allografts with weak osseous regions are usable, since bone remodeling replaces inferior quality bone. However, poor quality chondral surfaces on grafts preclude their use, leading to grafting material shortages. Endogenous adult stem cells can make hyaline-like cartilage tissue on scaffolds. To increase the number of usable allografts, tissue culture methods using adipose derived stem cells (ASCs) were developed to grow cartilage on grafts. METHODS: Co-cultures utilized living chondrocytes in host cartilage, modeling in vivo conditions, and ASCs seeded on the allografts. Sterilized allografts were treated with Poly-L-Lysine and ProNectin. Tissue growth was analyzed and quantified with histological techniques. RESULTS AND CONCLUSIONS: Monoculture experiments produced tenuous cartilage formation when proteins were utilized and allograft surfaces were perforated. Extensive tissue formation was observed with co-culture and the presence of type II collagen was confirmed with immunohistochemistry. Results demonstrate that co-culture techniques offer a better means of growing tissue on allograft cartilage surfaces. Additionally, the use of proteins to facilitate surface attachment produced more tissue formation demonstrating that cell attachment is crucial when growing cartilage on allografts. Development of new culture techniques to evaluate treatment strategies will accelerate the rate at which cartilage procedures using endogenous cells are possible. This will increase the number of usable grafts and allow critical selection of grafts to fit specific surfaces increasing surgical success by returning the joint to its native structure.