Kartogenin‐Conjugated Double‐Network Hydrogel Combined with Stem Cell Transplantation and Tracing for Cartilage Repair

Abstract

The effectiveness of existing tissue-engineering cartilage (TEC) is known to be hampered by weak integration of biocompatibility, biodegradation, mechanical strength, and microenvironment supplies. The strategy of hydrogel-based TEC holds considerable promise in circumventing these problems. Herein, a non-toxic, biodegradable, and mechanically optimized double-network (DN) hydrogel consisting of polyethylene glycol (PEG) and kartogenin (KGN)-conjugated chitosan (CHI) is constructed using a simple soaking strategy. This PEG-CHI-KGN DN hydrogel possesses favorable architectures, suitable mechanics, remarkable cellular affinity, and sustained KGN release, which can facilitate the cartilage-specific genes expression and extracellular matrix secretion of peripheral blood-derived mesenchymal stem cells (PB-MSCs). Notably, after tracing the transplanted cells by detecting the rabbit sex-determining region Y-linked gene sequence, the allogeneic PB-MSCs are found to survive for even 3 months in the regenerated cartilage. Here, the long-term release of KGN is able to efficiently and persistently activate multiple genes and signaling pathways to promote the chondrogenesis, chondrocyte differentiation, and survival of PB-MSCs. Thus, the regenerated tissues exhibit well-matched histomorphology and biomechanical performance such as native cartilage. Consequently, it is believed this innovative work can expand the choice for developing the next generation of orthopedic implants in the loadbearing region of a living body.

Functional injectable hydrogel with spatiotemporal sequential release for recruitment of endogenous stem cells and in situ cartilage regeneration

“…53 A recent study reported that MSCs maintained chondrocyte-like morphology in a KGN-conjugated hydrogel scaffold after culturing for 14 days. 54…”

Biomimetic Injectable Hydrogel Based on Methacrylate-Modified Silk Fibroin Embedded with Kartogenin for Superficial Cartilage Regeneration

“…In this study, we used KGN as a bioactive agent to induce chondrogenic differentiation. Many articles have demonstrated that KGN has the ability to significantly promote cartilage regeneration, and it is stable, easy to transport and store, is an ideal bioactive factor. ,, We combined it with SilMA hydrogels to achieve a continuous release of KGN while creating a mechanical environment for cartilage. Our results indicate that SilMA/KGN hydrogels has a significant ability to promote cartilage regeneration both in vivo and in vitro .…”

“…Therefore, KGN is a promising molecule for inducing cartilage regeneration. A series of articles have shown that KGN can effectively promote chondrogenic differentiation of stem cells. − …”

Ultrasound-triggered in situ gelation with ROS-controlled drug release for cartilage repair

“…32,33 These unique intrinsic features could be applied for drug delivery and tissue regeneration, so fibrin-based hydrogels could be designed by adjusting the components and concentrations of the precursors, including fibrinogen and thrombin. 34–37 In addition, numerous studies have reported that kartogenin (KGN), as a nonprotein small molecule drug, could significantly promote cartilage-specific gene expression in BMSCs in a dose-dependent manner without any toxicity. 38–42 Most importantly, a certain level of reactive oxygen species (ROS) in the tissue microenvironment could promote BMSC proliferation and induce differentiation into chondrocytes by stimulating the secretion of glycosaminoglycan.…”