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Updated: Jun 26, 2025
Optimizing Extracellular Vesicle Delivery Using a Core-Sheath 3D-Bioprinted Scaffold for Chronic Wound Management
Published on: February 28, 2025
circCDK13-loaded small extracellular vesicles accelerate healing in preclinical diabetic wound models
Qilin Huang1,2, Ziqiang Chu2,3, Zihao Wang2,3,4
1Tianjin Medical University, No. 22, Qixiangtai Road, Heping District, Tianjin, 300070, China.
Abstract:
Chronic wounds are a major complication in patients with diabetes. Here, we identify a therapeutic circRNA and load it into small extracellular vesicles (sEVs) to treat diabetic wounds in preclinical models. We show that circCDK13 can stimulate the proliferation and migration of human dermal fibroblasts and human epidermal keratinocytes by interacting with insulin-like growth factor 2 mRNA binding protein 3 in an N6-Methyladenosine-dependent manner to enhance CD44 and c-MYC expression. We engineered sEVs that overexpress circCDK13 and show that local subcutaneous injection into male db/db diabetic mouse wounds and wounds of streptozotocin-induced type I male diabetic rats could accelerate wound healing and skin appendage regeneration. Our study demonstrates that the delivery of circCDK13 in sEVs may present an option for diabetic wound treatment.
Insights
This study identifies circCDK13 as a therapeutic molecule for diabetic wound healing. Loading circCDK13 into small extracellular vesicles (sEVs) accelerated healing and skin regeneration in preclinical diabetic wound models.
Area of Science:
- Biomedical Engineering
- Molecular Biology
- Regenerative Medicine
Background:
- Chronic wounds, particularly in diabetic patients, represent a significant clinical challenge.
- Current treatments for diabetic wounds have limitations in efficacy and healing speed.
Purpose of the Study:
- To identify and characterize a novel therapeutic circular RNA (circRNA) for diabetic wound treatment.
- To engineer small extracellular vesicles (sEVs) for targeted delivery of the therapeutic circRNA.
- To evaluate the efficacy of circRNA-loaded sEVs in preclinical models of diabetic wound healing.
Main Methods:
- Identification of circCDK13 and its mechanism of action involving IGF2BP3 and N6-Methyladenosine (m6A) modification.
- Engineering of sEVs to overexpress circCDK13.
- Preclinical testing in db/db diabetic mice and streptozotocin-induced diabetic rats.
Main Results:
- CircCDK13 promotes fibroblast and keratinocyte proliferation and migration by enhancing CD44 and c-MYC expression.
- Engineered sEVs loaded with circCDK13 accelerated wound healing and skin appendage regeneration in diabetic mouse and rat models.
- Local subcutaneous injection of circCDK13-loaded sEVs demonstrated therapeutic potential.
Conclusions:
- CircCDK13 is a promising therapeutic agent for promoting diabetic wound healing.
- sEVs serve as an effective delivery vehicle for circCDK13, enhancing its therapeutic efficacy.
- This approach offers a potential new strategy for treating chronic diabetic wounds.
