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

Abstract

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.

New Insights into Cartilage Tissue Engineering: Improvement of Tissue-Scaffold Integration to Enhance Cartilage Regeneration

“…Significant tissue regeneration and integration were observed in cell-seeded porous scaffolds in comparison to autologous chondrocyte implantation [ 51 ]. Ideal porosity can even lead to satisfactory integration of cell-free scaffolds with native tissue and development of convenient off-the-shelf products [ 52 , 53 ]. Pore size and density of scaffolds affect ECM integrity and maturity.…”

Designing functional hyaluronic acid-based hydrogels for cartilage tissue engineering

“…Moreover, the HA-ELP hydrogel exhibited high antibacterial activity against drug-resistant bacteria after doping with zinc oxide (ZnO) nanoparticles, demonstrating good application potential in tissue engineering such as cartilage repair [ 50 ]. In addition, compared with natural polymers, synthetic polymers have also been reported to optimize mechanical properties and endow multifunctionality to HA-MA-based hydrogels [ 51 , 52 ]. Wu et al.…”

“…The hybrid scaffold had a suitable compressive modulus (1.5 ​MPa), good ROS-scavenging ability, and ability to regulate inflammation to accelerate hyaline cartilage regeneration. Moreover, the incorporation of hydrogel had a positive impact on the deposition of GAG and collagen II to integrate with surrounding tissues for neocartilage [ 51 ]. Ren et al.…”

Understanding Reactive Oxygen Species in Bone Regeneration: A Glance at Potential Therapeutics and Bioengineering Applications

“…Further, Wu et al has shown that ROS-sensing hydrogels can be combined with structural polymers to improve cartilage regeneration (X. Wu et al, 2021). This hybrid biomaterial allows for ROS-sensing technology, without the degradation of the structural framework that is needed for musculoskeletal applications.…”