Chitosan hydrogel/3D-printed poly(ε-caprolactone) hybrid scaffold containing synovial mesenchymal stem cells for cartilage regeneration based on tetrahedral framework nucleic acid recruitment

Articular cartilage (AC) injury repair has always been a difficult problem for clinicians and researchers. Recently, a promising therapy based on mesenchymal stem cells (MSCs) has been developed for the regeneration of cartilage defects. As endogenous articular stem cells, synovial MSCs (SMSCs) possess strong chondrogenic dif-ferentiation ability and articular specificity. In this study, a cartilage regenerative system was developed based on a chitosan (CS) hydrogel/3D-printed poly(epsilon-caprolactone) (PCL) hybrid containing SMSCs and recruiting tetrahedral framework nucleic acid (TFNA) injected into the articular cavity. TFNA, which is a promising DNA nanomaterial for improving the regenerative microenvironment, could be taken up into SMSCs and promoted the proliferation and chondrogenic differentiation of SMSCs. CS, as a cationic polysaccharide, can bind to DNA through electrostatic action and recruit free TFNA after articular cavity injection in vivo. The 3D-printed PCL scaffold provided basic mechanical support, and TFNA provided a good microenvironment for the proliferation and chondrogenic differentiation of the delivered SMSCs and promoted cartilage regeneration, thus greatly improving the repair of cartilage defects. In conclusion, this study confirmed that a CS hydrogel/3D-printed PCL hybrid scaffold containing SMSCs could be a promising strategy for cartilage regeneration based on chitosan-directed TFNA recruitment and TFNA-enhanced cell proliferation and chondrogenesis.