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

by Selleckchem | Oct 05 2023

Cartilage defects are usually caused by acute trauma and chronic degeneration. However, it is still a great challenge to improve the repair of articular cartilage defects due to the limited self-regeneration capacity of such defects. Herein, a novel ROS-responsive in situ nanocomposite hydrogel loaded with kartogenin (KGN) and bone marrow-derived stem cells (BMSCs) was designed and constructed via the enzymatic reaction of fibrinogen and thrombin. Meanwhile, a ROS-responsive thioketal (TK)-based liposome was synthesized to load the chondrogenesis-inducing factor KGN, the bioenzyme thrombin and an ultrasound-sensitive agent PpIX. Under ultrasound stimulation, the TK-based liposome was destroyed, followed by in situ gelation of fibrinogen and thrombin. Moreover, sustained release of KGN was realized by regulating the ultrasound conditions. Importantly, ROS generation and KGN release within the microenvironment of the in situ fibrin hydrogel significantly promoted chondrogenic differentiation of BMSCs via the Smad5/mTOR signalling pathway and effectively improved cartilage regeneration in a rat articular cartilage defect model. Overall, the novel in situ nanocomposite hydrogel with ROS-controlled drug release has great potential for efficient cartilage repair.

Comments:

The passage you provided describes a novel approach for improving the repair of articular cartilage defects. These defects can occur due to acute trauma or chronic degeneration and are challenging to repair because cartilage has limited self-regeneration capacity. The proposed solution involves the design and construction of a responsive nanocomposite hydrogel that is loaded with kartogenin (KGN) and bone marrow-derived stem cells (BMSCs).

The hydrogel is created by using an enzymatic reaction between fibrinogen and thrombin. Additionally, a responsive liposome based on a thioketal (TK) compound is synthesized to encapsulate KGN, thrombin, and an ultrasound-sensitive agent called PpIX. Under ultrasound stimulation, the TK-based liposome is destroyed, leading to the gelation of fibrinogen and thrombin in situ.

One of the key features of this system is the controlled release of KGN. By regulating the ultrasound conditions, sustained release of KGN is achieved. Within the microenvironment of the in situ fibrin hydrogel, reactive oxygen species (ROS) are generated, and KGN is released. This ROS-controlled drug release system promotes chondrogenic differentiation of BMSCs through the Smad5/mTOR signaling pathway.

The results of experiments using a rat articular cartilage defect model indicate that the novel in situ nanocomposite hydrogel, with its ROS-controlled drug release mechanism, effectively enhances cartilage regeneration. By promoting chondrogenic differentiation of BMSCs and regulating the signaling pathway, this approach has the potential to improve cartilage repair efficiently.

In summary, the described nanocomposite hydrogel loaded with KGN and BMSCs, and incorporating a ROS-responsive drug release system, shows promise for addressing the challenge of cartilage repair by facilitating cartilage regeneration.