Bone microenvironment regulative hydrogels with ROS scavenging and prolonged oxygen-generating for enhancing bone...

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Large bone defects pose significant clinical challenges due to impaired healing.
• Hypoxia and excessive reactive oxygen species (ROS) in bone defects delay natural regeneration.
• Maintaining an optimal oxygen balance is crucial for effective bone repair.

Purpose of the Study:

• To design and evaluate a novel hydrogel system for regulating the bone microenvironment.
• To develop a hydrogel capable of scavenging ROS and providing sustained oxygen release.
• To investigate the therapeutic potential of this hydrogel in promoting bone regeneration.

Main Methods:

• Development of ROS scavenging and responsive prolonged oxygen-generating hydrogels (CPP-L/GelMA).
• Incorporation of catalase (CAT) and ROS-responsive oxygen-releasing nanoparticles (PFC@PLGA/PPS) within liposomes (CCP-L) and GelMA hydrogels.
• In vitro assessment of oxygen generation and ROS scavenging capabilities.
• In vivo evaluation in a mice skull defect model, analyzing angiogenesis, osteogenesis, and osteoclastogenesis.
• Investigation of the underlying Nrf2-BMAL1-autophagy pathway.

Main Results:

• CPP-L/GelMA hydrogels successfully scavenged ROS and provided prolonged oxygen release (>2 weeks) in hypoxic conditions.
• The hydrogel significantly enhanced angiogenesis and osteogenesis while inhibiting osteoclastogenesis.
• Demonstrated excellent bone regeneration in a mice skull defect model.
• The therapeutic effects were linked to the Nrf2-BMAL1-autophagy pathway.

Conclusions:

• CPP-L/GelMA hydrogels effectively regulate the bone microenvironment by managing ROS and oxygen levels.
• This innovative hydrogel shows significant potential for enhancing bone tissue repair and regeneration.
• The study highlights the clinical therapeutic potential of CPP-L/GelMA for treating large bone defects.