Abstract
Inflammatory cells mount an immune response against in vitro engineered cartilage implanted into immunocompetent animals, consequently limiting the usage of tissue-engineered cartilage to repair cartilage defects. In this study, curcumin (Cur)-an anti-inflammatory agent-was mixed with poly(lactic-co-glycolic acid) (PLGA) to develop a Cur/PLGA nanofibrous membrane with nanoscale pore size and anti-inflammatory properties. Fourier-transform infrared spectroscopy and high-performance liquid chromatography analyses confirmed the successful loading of Cur into the Cur/PLGA nanofibrous membrane. The results of the in vitro assay demonstrated the sustained release kinetics and enhanced stability of Cur in the Cur/PLGA nanofibrous membrane. Western blotting and enzyme-linked immunosorbent assay analyses revealed that the Cur/PLGA nanofibrous membrane significantly downregulated the expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α). A chondrocyte suspension was seeded into a porous PLGA scaffold, and the loaded scaffold was cultured for 3 weeks in vitro to engineer cartilage tissues. The cartilage was packed with the in vitro engineered Cur/PLGA nanofibrous membrane and subcutaneously implanted into rats to generate an immunosuppressive niche. Compared with those in the PLGA-implanted and pure cartilage (without nanofibrous membrane package)-implanted groups, the cartilage was well preserved and the inflammatory response was suppressed in the Cur/PLGA-implanted group at weeks 2 and 4 post-implantation. Thus, this study demonstrated that packaging the cartilage with the Cur/PLGA nanofibrous membrane effectively generated an immunosuppressive niche to protect the cartilage against inflammatory invasion. These findings enable the clinical translation of tissue-engineered cartilage to repair cartilage defects.