A cell-free ROS-responsive hydrogel/oriented poly(lactide-co-glycolide) hybrid scaffold for reducing inflammation and restoring full-thickness cartilage defects in vivo

The modulation of inflammation in tissue microenvironment takes an important role in cartilage repair and regeneration. In this study, a novel hybrid scaffold was designed and fabricated by filling a reactive oxygen species (ROS)-scavenging hydrogel (RS Gel) into a radially oriented poly(lactide-co-glycolide) (PLGA) scaffold. The radially oriented PLGA scaffolds were fabricated through a temperature gradient-guided phase separation and freeze-drying method. The RS Gel was formed by crosslinking the mixture of ROS-responsive hyperbranched polymers and biocompatible methacrylated hyaluronic acid (HA-MA). The hybrid scaffolds exhibited a proper compressive modulus, good ROS-scavenging capability, and cell compatibility. In vivo tests showed that the hybrid scaffolds significantly regulated inflammation and promoted regeneration of hyaline cartilage after they were implanted into full-thickness cartilage defects in rabbits for 12 w. In comparison with the PLGA scaffolds, the neo-cartilage in the hybrid scaffolds group possessed more deposition of glycosaminoglycans and collagen type II, and were well integrated with the surrounding tissue.

Automated summary

The novel hybrid scaffold plays a crucial role in cartilage repair and regeneration by scavenging reactive oxygen species. It possesses proper compressive modulus, strong ROS-scavenging capability, and good cell compatibility. In vivo tests demonstrate that the hybrid scaffold significantly modulates inflammation and promotes hyaline cartilage regeneration, leading to superior deposition of glycosaminoglycans and collagen type II compared to traditional PLGA scaffolds.