ROS-Responsive Hydrogel Delivering METRNL Enhances Bone Regeneration via Dual Stem Cell Homing and Vasculogenesis...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Critical-sized bone defects impede natural healing due to a hostile microenvironment.
• This microenvironment is characterized by excessive reactive oxygen species (ROS), vascular damage, and insufficient osteoblasts.
• Restoring microenvironmental balance is crucial for effective bone repair.

Purpose of the Study:

• To develop a ROS-responsive hydrogel system for targeted delivery of METRNL to modulate the bone microenvironment.
• To investigate the potential of this system in promoting bone regeneration by enhancing stem cell recruitment and angiogenesis.
• To evaluate the therapeutic efficacy in a rat cranial bone defect model.

Main Methods:

• Development of a ROS-cleavable GelMA-based hydrogel (RRG-MRL) loaded with METRNL.
• In vitro assessment of ROS scavenging, METRNL release kinetics, and cellular responses (angiogenesis, stem cell recruitment).
• In vivo evaluation in a rat cranial bone defect model, assessing ROS levels, cell infiltration, neovascularization, and bone regeneration.

Main Results:

• The RRG-MRL hydrogel effectively scavenged ROS and released METRNL in response to oxidative stress.
• METRNL promoted endothelial cell angiogenesis via the c-Kit/PI3K/Akt pathway and enhanced bone marrow mesenchymal stem cell (BMSC) recruitment.
• In vivo studies showed reduced ROS, increased BMSCs, enhanced vascularization, and accelerated bone regeneration in treated defects.

Conclusions:

• The ROS-responsive METRNL-delivering hydrogel acts as a bone microenvironment-modulating system.
• This platform facilitates bone regeneration by restoring homeostasis, promoting cell homing, and enhancing angiogenesis.
• The developed system shows significant potential for clinical application in treating critical-sized bone defects.