Exosomes from rADSCs Stress-Preconditioned by Pathological Tissue Homogenate for Diabetic Wound Treatment

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Stem Cell Biology

Background:

• Diabetic wound healing is hindered by a pathological microenvironment.
• Existing exosome therapies lack comprehensive repair capabilities for diabetic wounds.

Purpose of the Study:

• To develop exosomes with enhanced regenerative functions for diabetic wound healing.
• To investigate the therapeutic potential of multiple stress-preconditioned exosomes.

Main Methods:

• Stimulating rat adipose-derived stem cells with diabetic wound homogenate (DWH) to produce exosomes (Aφ-exos).
• Proteomic and miRNA sequencing to analyze exosome content.
• In vitro assessment of fibroblast proliferation, macrophage polarization, and angiogenesis.
• In vivo evaluation of diabetic wound healing using GelMA hydrogel delivery.

Main Results:

• Multiple stress-preconditioned exosomes (A50-exos/A100-exos) upregulated pro-healing factors and downregulated anti-healing factors.
• A50-exos/A100-exos enhanced fibroblast activity, promoted M2 macrophage polarization, and improved angiogenesis in high-glucose conditions.
• In vivo, A50-exos/A100-exos delivered via hydrogel significantly accelerated diabetic wound healing by improving collagen deposition, inflammation modulation, and vascularization.

Conclusions:

• Biomimetic exosome engineering using microenvironment-specific reprogramming offers a potent cell-free therapeutic platform.
• This strategy precisely targets the multifaceted pathology of diabetic wounds for synergistic tissue regeneration.