uKnee

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uKnee is the first in vitro miniaturized model of a human osteoarthritic (OA) cartilage on chip, developed within uBeat® Compress. Healthy cartilage microconstructs are first generated from human articular chondrocytes embedded in an hydrogel and cultured in static condition for two weeks within uBeat® Compress. Thanks to BiomimX®  technology uBeat®, a mechanical overload resembling the OA pathological conditions is then applied to the healthy cartilage microtissues. uBeat® pathological stimulation leads within few days to the generation of OA-like microtissues with a phenotype and genotype correlating with OA clinical evidences.

uKnee provides measurement of the key indicators of OA, including anabolic-catabolic balance changes, occurrence of inflammation, production of matrix degrading enzymes and changes in key molecular pathways.

Animal models and alternative in vitro platforms are unable to mimic the human pathology to this extent. uKnee can thus be used to test the efficiency of potential new anti-OA candidates to reverse the pathology, being the first in vitro platform able to replicate OA disease.

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A healthy human cartilage microtissue is generated within uBeat® Compress

By culturing human healthy articular chondrocytes in static condition for two weeks within uBeat® Compress, a cartilage microtissue is obtained exhibiting a native-like deposition of extracellular matrix (abundant in collagen type-II and aggrecan) and a characteristic gene profile matching those of human cartilage.

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uBeat® mechanical overload induces an OA-like anabolic-catabolic balance change

uBeat® pathological stimulation induces a shift in cartilage homeostasis towards catabolism as evidenced by loss of expression of anabolic genes (COL2A1 and ACAN), increased production of MMP13 cartilage degrading enzymes and up-regulation of inflammation related genes (IL6 and IL8).

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uBeat® induces an OA-like gene profile

uBeat® pathological stimulation triggers the acquisition of a gene expression profile compatible with clinical evidences of OA. COL10A1 and IHH expression was upregulated, suggesting the triggering of a hypertrophic differentiation of the model towards transient calcified cartilage. GREM1, FRZB and DKK1 (BMP and Wnt signalling antagonists inversely correlated with OA onset) are downregulated upon uBeat® pathological stimulation, with levels matching those detected in native OA cartilage samples