Immune‑Friendly Skin Interface Remodeling: Chiral Hydrogels for Diabetic Non-Healing Wound Therapy.

Abstract

Diabetic non‑healing wounds pose a clinical challenge due to persistent inflammation, dysregulated immunity, and poor integration of dressings with the skin. Conventional hydrogel dressings have proven effective in providing physical barriers, moisture retention, and local drug delivery. Further optimization is still feasible for precise immune regulation and dynamic skin interfacial matching. In non-healing wound therapy, enantiomerically defined chiral hydrogels have emerged as a promising platform for targeted immune remodeling. By selectively steering macrophage polarization from pro-inflammatory M1 to pro-healing M2, they facilitate a smooth inflammatory-to-proliferative transition and accelerate wound closure. With rational network design, chiral hydrogels achieve favorable interfacial compatibility with the moist, dynamic wound environment, supporting cell adhesion, reducing friction induced microtrauma, sustaining bioactive signal delivery, and avoiding overt foreign body reactions. By integrating chiral topography, biomimetic mechanical properties, and moderate tissue adhesion, these hydrogels help establish an "immune-friendly" dermal interface. This review discusses structure-activity relationships linking chiral chemistry to immune cell behavior and outlines design principles for clinically translatable wound dressings. Collectively, chiral hydrogels that synergistically remodel immune microenvironment and ensure skin compatibility could redefine diabetic wound therapy, enabling a new paradigm of precision, immune‑instructive the wound management that transcends conventional dressing functions.