Given the multi-tissue aspects of osteoarthritis (OA) pathophysiology, translation of OA susceptibility genes towards underlying biological mechanism and eventually drug target discovery requires... Show moreGiven the multi-tissue aspects of osteoarthritis (OA) pathophysiology, translation of OA susceptibility genes towards underlying biological mechanism and eventually drug target discovery requires appropriate human in vitro OA models that incorporate both functional bone and cartilage tissue units. Therefore, a microfluidic chip is developed with an integrated fibrous polycaprolactone matrix in which neo-bone and cartilage are produced, that could serve as a tailored human in vitro disease model of the osteochondral unit of joints. The model enables to evaluate OA-related environmental perturbations to (individual) tissue units by controlling environmental cues, for example by adding biochemical agents. After establishing the co-culture in the system, a layer of cartilaginous matrix is deposited in the chondrogenic compartment, while a bone-like matrix is deposited between the fibers, indicated by both histology and gene expression levels of collagen type 2 and osteopontin, respectively. As proof-of-principle, the bone and cartilaginous tissue are exposed to active thyroid hormone, creating an OA disease model. This results in increased expression levels of hypertrophy markers integrin-binding sialoprotein and alkaline phosphatase in both cartilage and bone, as expected. Altogether, this model could contribute to enhanced translation from OA risk genes towards novel OA therapies. Show less
Velasco-Velez, J.J.; Jones, T.E.; Streibel, V.; Havecker, M.; Chuang, C.H.; Frevel, L.; ... ; Knop-Gericke, A. 2019
An electrode for the oxygen evolution reaction based on a conductive bi-layered free standing graphene support functionalized with iridium nanoparticles was fabricated and characterized by means of... Show moreAn electrode for the oxygen evolution reaction based on a conductive bi-layered free standing graphene support functionalized with iridium nanoparticles was fabricated and characterized by means of potentiometric and advanced X-ray spectroscopic techniques. It was found that the electrocatalytic activity of iridium nanoparticles is associated to the formation of Ir 5d electron holes. Strong Ir 5d and O 2p hybridization, however, leads to a concomitant increase O 2p hole character, making oxygen electron deficient and susceptible to nucleophilic attack by water. Consequently, more efficient electrocatalysts can be synthesized by increasing the number of electron-holes shared between the metal d and oxygen 2p. Show less
Hunt, K.A.; Smyth, D.J.; Balschun, T.; Ban, M.; Mistry, V.; Ahmad, T.; ... ; Wellcome Trust Case 2012
