Novel copper-ion coordinated andrographolide-loaded hydrogel activates Rac1/JNK1 axis for enhancing diabetic wound...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Wound Healing Research

Background:

• Chronic diabetic wounds pose significant clinical challenges due to persistent inflammation, infection, and poor blood vessel formation.
• Current treatments often fail to address the complex, multifactorial nature of these wounds.
• Andrographolide, a natural compound, has therapeutic potential but suffers from poor solubility.

Purpose of the Study:

• To develop and evaluate a novel copper-ion coordinated andrographolide-loaded hydrogel (ASFH) for enhanced diabetic wound healing.
• To investigate the in vitro and in vivo efficacy of ASFH in addressing key pathological features of diabetic wounds.
• To elucidate the underlying molecular mechanisms responsible for ASFH-mediated wound regeneration.

Main Methods:

• Fabrication and characterization of ASFH, assessing its physicochemical properties, antimicrobial activity, and cytocompatibility.
• In vivo studies using a diabetic mouse model to evaluate wound closure rate, tissue regeneration, and angiogenesis.
• Mechanistic investigations employing network pharmacology, molecular docking, dynamics simulations, and surface plasmon resonance (SPR) validation.

Main Results:

• ASFH exhibited excellent antimicrobial properties, mechanical strength, self-healing capacity, and biocompatibility in vitro.
• In diabetic mice, ASFH significantly accelerated wound closure, improved collagen deposition, promoted re-epithelialization, and enhanced angiogenesis.
• ASFH modulated macrophage phenotype towards an anti-inflammatory state and activated the Rac1/JNK1/Jun/Fos signaling pathway.

Conclusions:

• ASFH is a promising biomaterial dressing that effectively addresses multiple challenges in diabetic wound management.
• The hydrogel enhances wound healing by controlling inflammation, combating infection, and promoting vascularization.
• Targeted intervention via the Rac1/JNK1/Jun/Fos pathway is a key mechanism underlying ASFH's regenerative effects, offering a translationally relevant therapeutic strategy.