Evaluation of human explants as ex vivo models of disease

Osteoarthritis (OA) is a degenerative joint disease leading to cartilage degradation, subchondral bone sclerosis and thickening, and osteophyte formation (1). Moreover, trabecular bone in the subchondral region is thinned, and its elasticity is lost. The use of ex vivo explants are a powerful tool as a near in vivo culture model for bone research, namely for OA therapies assessment (2). With this in mind, it was hypothesized that human femoral head explants would be an optimal in vitro model to test newly designed scaffolds for OA treatment. For that, femoral head explants were obtained from total hip replacement surgery and under patients consent. Then, three holes of 8 mm depth and diameter were drilled and scaffolds of SF/SrZnTCP were placed inside. Thereafter, femoral heads were maintained in culture for 28 days. At day 7, 14, 21 and 28, the medium was collected in order to quantify alkaline phosphatase (ALP) and glycosaminoglycans (GAGs) and at days 14, 21 and 28 the metabolic activity was assessed using resazurin reagent. Finally, at day 28, explants were analysed using peripheral quantitative computed tomography. The results showed a decrease of ALP activity along the time as expected but the levels of GAGs were maintained. Moreover, despite the decrease of metabolic activity along the time, it was clear the femoral heads were viable until the end of culture. Finally, the peripheral quantitative computed tomography showed no gap between the scaffolds and the femoral heads, which indicates a good integration of the scaffolds. Nevertheless, histological analysis will be necessary for further assessment.  Overall, the results supported the use of explants to test new developed scaffold in a near in vivo environment.