Fig. 3

Dual targeting, SMSC recruitment, and chondroinductivity of NPs. a Fluorescence images of rat knee joint sections following intraarticular injection of Cy5.5-labled WPV-CuO NPs. WPV-CuO actively penetrated cartilage, even in the presence of MMP-2. Scale bar = 100 μm. b Fluorescence images of SMSCs treated with Cy5.5-labeled NPs and MMP-2. Scale bar = 100 μm. c Flow cytometry analysis showing highest mean fluorescence intensity (MFI) of SMSCs in the WPV-CuO NP group. Bars represent mean ± SD (n = 3). d Representative SEM images of SMSC recruitment (highlighted by red arrows) in rat tibial plateau after treatment with NPs and MMP-2. e Calculation of the number of SMSCs attached to rat tibial plateau from five random SEM images. The data indicate that WPV-CuO NPs home into cartilage and expose the inner MSC targeting peptide due to MMP-2 sensitivity, leading to significant enhancement of SMSC adhesion to cartilage. Bars represent mean ± SD (n = 5). f Relative expression levels of chondrogenic genes in SMSCs co-cultured with NPs. Bars represent mean ± SD (n = 3). g Immunohistological staining of COL2 in SMSC cell pellets co-cultured with NPs. Scale bar = 200 μm. *p < 0.05, **p < 0.01, #p < 0.05, ##p < 0.01