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

TLDR

Articular cartilage injury repair remains challenging, but mesenchymal stem cell therapies—especially synovial MSCs with strong chondrogenic potential—offer promising solutions. This study aimed to create a cartilage regenerative system combining a chitosan hydrogel/3D‑printed poly(ε‑caprolactone) scaffold loaded with synovial MSCs and recruiting tetrahedral framework nucleic acid (TFNA) into the joint cavity. Chitosan electrostatically binds TFNA, recruiting it to the scaffold, while TFNA is internalized by the MSCs to stimulate their proliferation and chondrogenic differentiation, and the PCL scaffold supplies mechanical support. The hybrid scaffold with SMSCs and TFNA markedly enhanced cartilage regeneration, leading to significantly improved repair of cartilage defects.

Abstract

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 differentiation ability and articular specificity. In this study, a cartilage regenerative system was developed based on a chitosan (CS) hydrogel/3D-printed poly(ε‐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.