A poly (L-glutamic acid)-based porous scaffold with controllable and sequential release of kartogenin for enhanced cartilage regeneration

Abstract

The controllable and sequential release of kartogenin (KGN) could improve in situ cartilage regeneration due to the intrinsically different windows between endogenous stem/progenitor cells (ESPCs) recruitment and chondrogenesis. In this paper, KGN were loaded into polyamino acid-based scaffolds in two different ways: First, phenylboronic acid ester (PBE) covalent grafting between KGN and poly (L-glutamic acid) (PLG) was built for a responsive release in an inflammatory environment, showing a responsive release of 50 % in 3 days and effectively promoting the migration of bone marrow stem cells (BMSCs) in vitro. Secondly, the conformation shift of silk fibroin (SF), from hydrophilic α-helix to hydrophobic β-sheet, could form physical network for mechanical improvement of hydrogels, as well as embedding KGN for a sustained release of 73 % in 30 days, which promoted chondrogenesis of BMSCs. In vivo rat models proved scaffolds with ROS-responsive release and physical diffusion of KGN could successfully reconstruct hyaline cartilage whose matrix composition, distribution and structure were all consistent with healthy hyaline cartilage. These results proved that this work built a smart scaffold platform with controllable and sequential release of KGN, providing a new idea for cell-free strategy in cartilage regeneration and has great clinic meaning.