# A Time‐Programmed Bilayer Wound Dressing for Dynamic Microenvironment Modulation and Full‐Thickness Regeneration in Diabetic Wounds

## TL;DR

A new bilayer wound dressing helps diabetic wounds heal by reducing inflammation and promoting tissue regeneration through timed delivery of polyphenols and growth factors.

## Contribution

A novel bilayer dressing with chronotherapeutic properties for dynamic modulation of diabetic wound microenvironments.

## Key findings

- The bilayer system reduced inflammatory markers within 72 hours in a diabetic wound model.
- The dressing accelerated re-epithelialization and hair follicle regeneration within 7 to 21 days.

## Abstract

Chronic diabetic wounds suffer from dysfunctional repair programs due to accumulated advanced glycation end products (AGEs) and persistent inflammation in hyperglycemic microenvironments, posing significant clinical challenges. Current dressings predominantly focus on monofunctional interventions, failing to resolve the “inflammation‐repair imbalance”. In this study, we propose a chronotherapeutic bilayer system designed for stage specific regulation. The lower GelMA cryogel loaded with polyphenols acts as a “cleaner”, removing AGEs via hydrogen bond capture and pore entrapment and activating the PPARγ pathway to remodel the anti‐inflammatory microenvironment; The upper polycaprolactone nanofibers directionally deliver PDGF‐BB, enabling sustained release to activate fibroblast migration and angiogenesis. Additionally, proteomics analysis further revealed that polyphenols downregulate multiple inflammatory factors via the PPARγ/NF‐κB axis, providing a clean basal microenvironment for diabetes. In a diabetic wound model, the system demonstrated a three‐step healing, marked downregulation of inflammatory markers within 72 h, accelerated re‐epithelialization in 7 days, and functional hair follicle regeneration in 21 days. This study highlights the potential of “Clean‐Regeneration Dual Program” bilayer assembled scaffolds in modulating the wound microenvironment and promoting tissue regeneration.

The Polyphenol+PDGF‐BB scaffold fabrication (Panel A) and its dual wound healing effects (Panel B: anti‐inflammation and accelerated tissue remodeling).