Local Delivery of PHD2 siRNA from ROS-Degradable Scaffolds to Promote Diabetic Wound Healing

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Molecular Biology

Background:

• Diabetic wounds exhibit impaired healing due to complex pathophysiological factors.
• Targeted delivery of therapeutic agents is crucial for effective diabetic wound management.
• Reactive oxygen species (ROS)-degradable scaffolds offer controlled release of therapeutic payloads.

Purpose of the Study:

• To investigate the efficacy of siRNA delivered via ROS-degradable scaffolds for promoting diabetic wound healing.
• To evaluate the impact of inhibiting prolyl hydroxylase domain protein 2 (PHD2) on diabetic wound repair.
• To assess the scaffold's ability to enhance vascularization and cell proliferation in vivo.

Main Methods:

• Development of porous poly(thioketal-urethane) scaffolds designed for ROS degradation.
• Implantation of scaffolds loaded with siRNA targeting PHD2 into experimentally induced diabetic rat wounds.
• Assessment of wound healing parameters, including tissue regeneration, vasculature, and cell proliferation.
• Gene expression analysis to confirm inhibition of PHD2 and upregulation of progrowth factors.

Main Results:

• Scaffolds successfully delivered siRNA locally within the diabetic wound environment.
• Inhibition of PHD2 expression was confirmed, leading to increased expression of progrowth genes.
• Significant improvements in vasculature, proliferating cells, and overall tissue development were observed in treated wounds.
• ROS-degradable scaffolds facilitated controlled siRNA release and degradation.

Conclusions:

• siRNA delivered from ROS-degradable tissue engineering scaffolds effectively promotes diabetic wound healing in rats.
• Targeted inhibition of PHD2 using this delivery system enhances vascularization and tissue regeneration.
• This strategy represents a promising therapeutic approach for managing chronic diabetic wounds.