Transformation of human chondrocytes with copper-containing metal-organic biohybrids (MOBs)

Copper is involved in the biosynthesis of collagen, however soluble copper salts dissipate quickly and copper nanoparticles are cytotoxic. Here we added a novel copper-containing nanomaterial (CuHARS) to assess human chondrocyte function in the presence of copper. Human dermal fibroblasts (HDFs) were also treated as a control. Chondrocyte response to CuHARS was assessed by chronic nanomaterial treatment (30 µg/ml) followed by digital microscopy and image analysis of cellular features compared to normal chondrocytes. Unexpectedly, chronic CuHARS treatment of human chondrocytes transformed cells over time to cells with extremely elongated and variegated processes and lower proliferation rates compared to normal chondrocytes. In these transformed cells, which we named 3G, shedding of fine processes was observed over time and collected supernatants demonstrated elevated collagen levels compared to normal cell culture media. In contrast to chondrocytes, HDFs treated with CuHARS showed attenuated changes in morphology, and notably retained a prominent ability for continued proliferation. These results demonstrate that a copper-containing biohybrid material (CuHARS) can stably transform human chondrocytes with highly altered morphology, lower proliferation rates, and altered membrane dynamics compared to normal chondrocytes. In contrast, human dermal fibroblasts demonstrated attenuated changes in morphology, and retained an enhanced ability for proliferation. ### Competing Interest Statement The authors have declared no competing interest.