A Time-Programmed Bilayer Wound Dressing for Dynamic Microenvironment Modulation and Full-Thickness Regeneration in...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Wound Healing

Background:

• Chronic diabetic wounds exhibit impaired repair due to advanced glycation end products (AGEs) and hyperglycemia-induced inflammation.
• Existing wound dressings offer limited, monofunctional interventions, failing to address the complex inflammation-repair imbalance.

Purpose of the Study:

• To develop and evaluate a chronotherapeutic bilayer system for stage-specific regulation of diabetic wound healing.
• To investigate the efficacy of a dual-program scaffold in clearing AGEs, modulating inflammation, and promoting tissue regeneration.

Main Methods:

• Fabrication of a bilayer scaffold with a lower GelMA cryogel (polyphenols) and an upper polycaprolactone nanofiber layer (PDGF-BB).
• Assessment of AGEs removal, anti-inflammatory effects via PPARγ/NF-κB axis, and fibroblast activation.
• In vivo evaluation in a diabetic wound model, analyzing healing stages, inflammatory markers, re-epithelialization, and follicle regeneration.

Main Results:

• The bilayer system effectively removed AGEs and activated the PPARγ pathway, reducing inflammation.
• Polyphenols downregulated inflammatory factors through the PPARγ/NF-κB axis, creating a conducive microenvironment.
• The scaffold demonstrated a three-step healing process: inflammation reduction (72h), accelerated re-epithelialization (7 days), and hair follicle regeneration (21 days).

Conclusions:

• The developed
• Clean-Regeneration Dual Program
• bilayer scaffold effectively modulates the diabetic wound microenvironment.
• This chronotherapeutic system shows significant potential for promoting comprehensive tissue regeneration in chronic diabetic wounds.