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Updated: Sep 5, 2025
Optimizing Extracellular Vesicle Delivery Using a Core-Sheath 3D-Bioprinted Scaffold for Chronic Wound Management
Published on: February 28, 2025
Tetrahedral framework nucleic acids-based delivery promotes intracellular transfer of healing peptides and
Shiyu Lin1, Qi Zhang2,3,4,5, Songhang Li6
1Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China.
Objectives:
Peptide-based therapeutics are natural candidates to desirable wound healing. However, enzymatic surroundings largely limit its stability and bioavailability. Here, we developed a tetrahedral framework nucleic acids(tFNA)-based peptide delivery system, that is, p@tFNAs, to address deficiencies of healing peptide stability and intracellular delivery in diabetic wound healing.
Materials And Methods:
AGEs (advanced glycation end products) were used to treat endothelial cell to simulate cell injury in diabetic microenvironment. The effects and related mechanisms of p@tFNAs on endothelial cell proliferation, migration, angiogenesis and ROS (reactive oxygen species) production have been comprehensively studied. The wound healing model in diabetic mice was photographically and histologically investigated in vivo.
Results:
Efficient delivery of healing peptide by the framework(tFNA) was verified. p@tFNAs helped overcome the angiogenic obstacles induced by AGEs via ERK1/2 phosphorylation. In the meantime, p@tFNA exhibited its antioxidative property to achieve ROS balance. As a result, p@tFNA improved angiogenesis and diabetic wound healing in vitro and in vivo.
Conclusions:
Our findings demonstrate that p@tFNA could be a novel therapeutic strategy for diabetic wound healing. Moreover, a new method for intracellular delivery of peptides was also constructed.
