Osteoarthritis of the knee and spine is highly prevalent in modern society, yet a disease-modifying pharmacological treatment remains an unmet clinical need. A major challenge for drug development includes selection of appropriate preclinical models that accurately reflect clinical phenotypes of human disease. The aim of this study was to establish an ex vivo explant model of human knee and spine osteoarthritis that enables assessment of osteochondral tissue responses to inflammation and drug treatment. Equal-sized osteochondral fragments from knee and facet joints (both n = 6) were subjected to explant culture for 7 days in the presence of a toll-like receptor 4 (TLR4) agonist and an inhibitor of transforming growth factor-beta (TGF-β) receptor type I signaling. Markers of inflammation, interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), but not bone metabolism (pro-collagen-I) were significantly increased by treatment with TLR4 agonist. Targeting of TGF-β signaling resulted in a strong reduction of pro-collagen-I and significantly decreased IL-6 levels. MCP-1 secretion was increased, revealing a regulatory feedback mechanism between TGF-β and MCP-1 in joint tissues. These findings demonstrate proof-of-concept and feasibility of explant culture of human osteochondral specimens as a preclinical disease model, which might aid in definition and validation of disease-modifying drug targets.

Anterior cruciate ligament (ACL) injuries are common in sports and often require surgical intervention, e.g., ACL reconstruction (ACLR), aimed at restoring knee stability and enabling a return to pre-injury activity levels. The choice of graft is crucial, impacting biomechanical properties, clinical outcomes, and complication rates, and is especially important in revision surgeries after graft failure. Over the past 30 years, trends in graft selection have evolved towards more individualized approaches, considering factors such as patient activity level, prior injuries, and tissue availability. In Europe, autografts like hamstring tendon (HT), bone-patellar tendon-bone (BTB), and quadriceps tendon (QT) are preferred, with the increasing use of QT grafts. This review synthesizes the current literature on graft selection and its influence on ACLR outcomes.