HydroWrap for T2DM-Related Fractures: A smart H₂S-delivery controller modulating Macrophage senescence

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Diabetology

Background:

• Type 2 diabetes mellitus (T2DM) significantly impairs fracture healing due to a pro-inflammatory bone microenvironment.
• Macrophage senescence and reduced hydrogen sulfide (H2S) levels are key contributors to this impaired healing process.
• Senescence-associated secretory phenotypes (SASP) exacerbate the negative effects on bone healing.

Purpose of the Study:

• To develop an advanced H2S-delivery system, HydroWrap, to modulate macrophage senescence in T2DM.
• To investigate the therapeutic potential of HydroWrap in improving fracture healing in a T2DM context.
• To explore the glucose-responsive and NIR-triggered H2S release mechanism of HydroWrap.

Main Methods:

• Development of HydroWrap, a hydrogel-based H2S delivery controller.
• Utilizing near-infrared (NIR) irradiation to trigger temperature-dependent H2S release from HydroWrap.
• Assessing the impact of HydroWrap on macrophage senescence, mitochondrial dysfunction, and SASP.
• Evaluating fracture healing in an in vivo T2DM model.

Main Results:

• HydroWrap effectively modulated macrophage senescence by restoring H2S levels, alleviating mitochondrial dysfunction, and suppressing SASP.
• The system demonstrated sustained, glucose-responsive H2S release in a hyperglycemic environment.
• In vivo studies showed significantly accelerated fracture healing and enhanced bone quality in T2DM models treated with HydroWrap.
• HydroWrap promoted mitophagy and prevented macrophage senescence progression.

Conclusions:

• HydroWrap is a promising biocompatible drug delivery system for modulating macrophage senescence.
• This H2S-delivery approach offers a novel therapeutic strategy for improving fracture healing in diabetic patients.
• The findings suggest broader applications for HydroWrap in treating senescence-related diseases.