2. Academic Validation
  3. Versatile DNA Hydrogel-Mediated Delivery of Ginsenoside-Encapsulated Small Extracellular Vesicles to Boost Diabetic Wound Repair

Versatile DNA Hydrogel-Mediated Delivery of Ginsenoside-Encapsulated Small Extracellular Vesicles to Boost Diabetic Wound Repair

  • Adv Sci (Weinh). 2026 Jan 15:e22920. doi: 10.1002/advs.202522920.
Jianming Xing 1 2 3,  Shuangyang Li 1 2 3,  Yuning Wang 4,  Xushuang Jia 1 2 3,  Ruiting Lin 1 2 3,  Xintong Liu 1 2 3,  Dongxu Wang 5,  Ning Cui 1 2,  Peng Ji 1 2 3,  Jiaqi Chen 1 2 3,  Shengnian Wang 6,  Guangzhe Li 1 3,  Ye Teng 1 3,  Da Liu 1 3,  Ye Jin 1 2
Affiliations

Affiliations

  • 1 Changchun University of Chinese Medicine, Changchun, China.
  • 2 Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China.
  • 3 Public Experimental Center, Changchun University of Chinese Medicine, Changchun, China.
  • 4 Shanghai Key Lab of Reproduction and Development Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Obstetrics & Gynecology Hospital, Fudan University, Shanghai, China.
  • 5 Laboratory Animal Center College of Animal Science, Jilin University, Changchun, China.
  • 6 Institute For Micromanufacturing, Louisiana Tech University, Ruston, LA, USA.
PMID: 41538424 DOI: 10.1002/advs.202522920
Abstract

Diabetic wound healing is often hindered by poor outcomes, prolonged recovery, and high recurrence. To address this, a new therapy approach was demonstrated in this study, in which ginsenoside (GS) molecules are incorporated into small extracellular vesicles (sEV) secreted by mesenchymal stem cells (MSCs), and the formed complexes are then anchored in DNA hydrogels via aptamer-CD63 affinity as "GS/sEV@DNAgels". Besides the tissue-restorative ability that sEVs inherit from MSCs, in GS/sEV@DNAgels, GS molecules provide a superior antimicrobial/anti-inflammatory environment at wound sites, while DNA hydrogels serve as wound dressings to ensure sustained release kinetics and enhanced skin penetration. An innovative ultrasonic stimulation was developed to promote the massive production of sEVs. By triggering multiple cellular responses that alter membrane fluidity, calcium levels, and relevant protein expression, our approach achieves a 57.7-fold increase in sEV yield. The synergistic effects of GS and sEVs enhance cell viability, migration, and angiogenesis, as well as local anti-inflammatory and Antibacterial conditions during diabetic wound healing. The upregulation of miR-424/322 is confirmed as an essential mechanism of this GS/sEV@DNAgel system in accelerating skin restoration. Our work provides a new and promising strategy for diabetic tissue regeneration.

Keywords

DNA hydrogel; diabetic wound healing; extracellular vesicle; ginseng saponin; mesenchymal stem cell.

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