Core-Shell Codelivery Nanocarrier Synergistically Regulates Cartilaginous Immune Microenvironment for Total Meniscus...

Cartilage tissue engineering has made significant strides in clinical regenerative treatment. The success of cartilage regeneration critically depends on a favorable regenerative microenvironment by means of ideal bioactive scaffolds. However, total meniscus replacement frequently entails a harsh microenvironment of accompanying chronic inflammation and oxidative stress conditions after a massive injury, which extremely hinders tissue regenerative repair. Herein, a "core-shell" codelivery nanocarrier is developed to synergistically regulate the cartilaginous immune microenvironment (CIME) for total meniscus replacement. In this study, mesoporous silica nanoparticles are used to encapsulate an antioxidant and anti-inflammatory drug, Emodin, in the core and meanwhile modify a growth differentiation factor (GDF) by reversible disulfide bonds on the shell, together constructing a codelivery nanocarrier system (Em@MSN-GDF). The synergistic dual-drug release effectively reverses inflammation and oxidative microenvironment and is followed by successful promotion of fibrocartilage regeneration in vivo. Subsequently, Em@MSN-GDF-loaded cartilage-specific matrix hydrogels are combined with a meniscus-shaped polycaprolactone framework to construct a mechanically reinforced living meniscus substitute. As a result, rabbit experiments demonstrate that the codelivery nanocarrier system synergistically regulates the cartilaginous immune microenvironment, thereby achieving successful total meniscus replacement and fibrocartilage regeneration. The current study, therefore, offers a regenerative nanotreatment strategy to reverse the harsh microenvironment for total meniscus replacement.