Reprogramming the Diabetic Wound Microenvironment by Enzyme Cascade-Driven, ROS-Responsive Microspheres

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Wound Healing

Background:

• Diabetic wounds exhibit delayed healing due to hyperglycemia, oxidative stress, and hypoxia.
• The wound microenvironment in diabetes impairs angiogenesis and tissue regeneration.
• Current treatments struggle to address the complex dysregulation in diabetic wound healing.

Purpose of the Study:

• To develop a multifunctional microsphere system for simultaneous regulation of glucose, oxygen, and oxidative stress in diabetic wounds.
• To investigate the therapeutic efficacy of ROS-responsive curcumin nanoparticles integrated with glucose oxidase (GOx) and catalase (CAT) for wound healing.
• To restore homeostasis in the diabetic wound microenvironment for accelerated tissue regeneration.

Main Methods:

• Fabrication of a multifunctional microsphere system incorporating ROS-responsive curcumin nanoparticles, GOx, and CAT.
• Utilizing GOx to reduce glucose and generate hydrogen peroxide (H2O2), followed by CAT-mediated H2O2 decomposition to produce oxygen.
• Employing ROS-responsive nanoparticles for on-demand curcumin release in oxidative environments.

Main Results:

• The microsphere system effectively reduced glucose levels, generated oxygen, and scavenged ROS.
• Enhanced angiogenesis, fibroblast migration, and accelerated wound healing were observed.
• Histological analyses confirmed reduced inflammation, increased vascularization, and improved tissue regeneration.

Conclusions:

• The developed microsphere system demonstrates a promising strategy for diabetic wound management.
• Coordinated enzymatic cascades and ROS-responsive drug delivery restore wound microenvironment homeostasis.
• The Cur/Enzyme/Nanoclay@Microsphere formulation showed significant therapeutic benefits.