Glucose-Responsive Fibrin Hydrogel-Based Multimodal Nucleic Acid Delivery System.

Area of Science:

• Biomaterials Science
• Gene Therapy
• Wound Healing Research

Background:

• Nucleic acid therapy offers potential for wound healing via gene expression modification.
• Challenges include nucleic acid protection, bioresponsive delivery, and cellular transfection.
• A glucose-responsive system is ideal for diabetic wound treatment, enabling regulated delivery.

Purpose of the Study:

• To design and evaluate a glucose-responsive gene delivery system for diabetic wounds.
• To assess the system's ability to load and release nucleic acids effectively and safely.
• To investigate the therapeutic effects of the system on wound healing in a diabetic mouse model.

Main Methods:

• Fabrication of fibrin-coated polymeric microcapsules (FCPMC) using a layer-by-layer approach.
• Loading of nucleic acids into polyplexes within the FCPMC system.
• In vitro cytotoxicity assessment and in vivo studies on diabetic db/db mice wounds.

Main Results:

• The FCPMC system efficiently loaded and sustained nucleic acid release with no observed cytotoxicity.
• In vivo application to diabetic wounds showed improved reepithelialization and angiogenesis.
• The system significantly decreased inflammation and upregulated key wound healing proteins (Actn2, MYBPC1, desmin).

Conclusions:

• The developed glucose-responsive fibrin hydrogel (GRFHG) effectively promotes wound healing in a diabetic context.
• The system demonstrates potential for co-delivery of multiple therapeutic nucleic acids.
• This biomaterial offers a promising strategy for managing diabetic wound complications.